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. 2025 Apr 30;14(9):3120.
doi: 10.3390/jcm14093120.

Planned vs. Performed Treatment Regimens in Diabetic Macular Edema: Real-World Evidence from the PACIFIC Study

Christos Haritoglou  1 , Matthias Iwersen  2 , Bettina Müller  2 , Erik Beeke  3 , Hüsnü Berk  4 , Matthias Grüb  5 , Katrin Lorenz  6 , Martin Scheffler  7 , Focke Ziemssen  8   9 ; PACIFIC Study Group
Affiliations

Planned vs. Performed Treatment Regimens in Diabetic Macular Edema: Real-World Evidence from the PACIFIC Study

Christos Haritoglou et al. J Clin Med. .

Abstract

Background: Intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are standard for diabetic macular edema (DME), yet a gap exists between clinical guidelines and actual practices. This study aimed to investigate the extent of deviation between physician-planned and actually performed treatment regimens. Methods: The PACIFIC study (NCT04847895) was a prospective, multicenter, non-interventional study conducted in Germany, the Netherlands, and Switzerland. A total of 910 patients with DME receiving ranibizumab were enrolled. Physicians documented the intended treatment regimen at baseline, and actual treatment patterns were retrospectively derived from the timing of visits and injections over a 24-month observation period. Results: Although most physicians initially planned fixed or pro re nata (PRN) regimens, 77% of pretreated and 73% of treatment-naïve patients ultimately followed a monitor and extend strategy. Treatment discontinuation was frequent (58.8% and 59.4%, respectively), and injection frequencies remained below recommended levels, although central retinal thickness improved over time. Conclusions: The study highlights a consistent and clinically relevant discrepancy between planned and actual treatment delivery in DME care, underscoring the need for better adherence to guideline-informed strategies in routine practice.

Keywords: clinical guidelines; diabetic macular edema (DME); intravitreal injections; observational study; patient-centered care; real-world evidence; treatment adherence; treatment deviations; treatment strategies; vascular endothelial growth factor (VEGF) inhibitors.

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Conflict of interest statement

Christos Haritoglou received honoraria as a speaker from Novartis, Bayer, and Allergan/AbbVie. Matthias Iwersen and Bettina Müller are employees of Novartis Pharma GmbH, Germany. Erik Beeke received a grant from Novartis. Hüsnü Berk declares no conflicts of interest outside the study participation fees. Matthias Grüb received grants from Novartis and Bayer and personal fees from Novartis. Katrin Lorenz received honoraria from Ethikkommission der Landesärztekammer Rheinland-Pfalz and Novartis Pharma GmbH, travel grants from Novartis Pharma GmbH, and participated in the following clinical trials/grants: Aerie, Allergan, Amgen, Bayer, Chengdu Kanghong Biotechnology Co., Hexal, Hoya, iStar, Iveric Bio, Janssen Cilag, Implandata, Lumithera, Microoptx, Mylan, Novartis, Ophtea limited, Pfizer, Redwood, Roche, Sensimed, and Santen. Martin Scheffler declares no conflicts of interest outside the study participation fees. Focke Ziemssen received grants or personal fees from Acelyrin, Alimera, Allergan/Abbvie, Apellis, Bayer Healthcare, BDI, Biogen, Boehringer-Ingelheim, Clearside, CME Health, Ionis, Janssen, Kodiak, Novartis, NovoNordisk, MSD Sharp & Dohme, Oxurion, ODOS, Ophtea, Regeneron, Roche/Genentech, Sandoz, Sanofi, and Stada.

Figures

Figure A1
Figure A1
Concomitant laser treatment over the 24-month observational period for pre-treated patients.
Figure A2
Figure A2
Cumulative percentages of concomitant laser treatments for pre-treated and treatment-naïve patients.
Figure A3
Figure A3
Actually performed treatment regimens over the 24-month observational period for pre-treated patients.
Figure A4
Figure A4
Actually performed treatment regimens over the 24-month observational period for treatment-naïve patients.
Figure A5
Figure A5
Central retinal thickness (CRT) by month for pre-treated patients.
Figure A6
Figure A6
Central retinal thickness (CRT) by month for treatment-naïve patients.
Figure 1
Figure 1
Concomitant laser treatment over the 24-month observational period for treatment-naïve patients.
Figure 2
Figure 2
Intended treatment regimens at baseline and actual treatment regimens in the last month for pretreated (a) and treatment-naïve (b) patients. Percentages are based on non-missing observations. In total, 443 pretreated patients had observations in the last month. Information on the treatment regimen was missing for 26 patients, and for 43 patients, the intended treatment regimen was changed during the study; therefore, these patients are not included in this figure. Of the 443 naïve patients with observations in the last month, 16 patients were missing information, and the intended treatment regimen was changed for 35 patients.
Figure 3
Figure 3
BCVA by month, logMAR, and ETDRS values for pretreated (a) and treatment-naïve patients (b).
See this image and copyright information in PMC

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