December 2024
Volume 65, Issue 14
Open Access
Retina  |   December 2024
Real-World Outcomes After Switch From Aflibercept to Faricimab in Eyes With Diabetic Macular Edema
Author Affiliations & Notes
  • Kim Lien Huber
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Heiko Stino
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Irene Steiner
    Medical University of Vienna, Center for Medical Data Science, Institute of Medical Statistics, Vienna, Austria
  • Philipp Fuchs
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Felix Goldbach
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Julia Mai
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Bianca S. Gerendas
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Katharina Kriechbaum
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Ursula Schmidt-Erfurth
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Andreas Pollreisz
    Medical University of Vienna, Department of Ophthalmology, Vienna, Austria
  • Correspondence: Andreas Pollreisz, Department of Ophthalmology and Optometry, Medical University of Vienna Währinger Gürtel 18-20, Vienna 1090, Austria; [email protected]
Investigative Ophthalmology & Visual Science December 2024, Vol.65, 46. doi:https://doi.org/10.1167/iovs.65.14.46
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      Kim Lien Huber, Heiko Stino, Irene Steiner, Philipp Fuchs, Felix Goldbach, Julia Mai, Bianca S. Gerendas, Katharina Kriechbaum, Ursula Schmidt-Erfurth, Andreas Pollreisz; Real-World Outcomes After Switch From Aflibercept to Faricimab in Eyes With Diabetic Macular Edema. Invest. Ophthalmol. Vis. Sci. 2024;65(14):46. https://doi.org/10.1167/iovs.65.14.46.

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Abstract

Purpose: To assess the anatomic and functional outcomes in eyes with diabetic macular edema (DME) switched from intravitreal aflibercept to faricimab in a real-world setting.

Methods: Retrospective, interventional consecutive case series. Patients with DME were switched from aflibercept to faricimab and categorized based on central subfield thickness (CST) 4 weeks after last aflibercept injection into responding DME (rDME, CST reduction >20% or CST ≤ 250 µm) and nonresponding DME (nrDME, CST unchanged or increased). Patients received a loading dose of two monthly faricimab injections followed by a treat-and-extend regimen. Differences in response between rDME and nrDME were analyzed based on injection interval, change in CST, and visual acuity (VA) 12 weeks postswitch.

Results: Fifty-two eyes of 40 patients met inclusion criteria (rDME: n = 26, nrDME: n = 26). Baseline and week 12: VA (logMAR) rDME 0.29 ± 0.23 and 0.22 ± 0.28, nrDME 0.42 ± 0.32 and 0.36 ± 0.29; CST (µm) rDME 370 ± 99 and 288 ± 80, nrDME 384 ± 85 and 380 ± 129. After 12 weeks, 54% rDME and 25% nrDME eyes showed a CST decrease of >20% or CST ≤ 250 µm. Forty-six percent rDME and 50% nrDME eyes had a ±20% CST change, 25% of nrDME eyes had a >20% CST increase, and 73% of rDME eyes and 47% of nrDME eyes reached an extended interval of 8 weeks or longer after 12 weeks.

Conclusions: Most DME eyes previously responding or not responding to aflibercept experienced a reduction or stabilization of DME after 12 weeks of faricimab treatment. rDME showed a better anatomic response, and treatment intervals could be extended earlier and longer than nrDME.

Diabetic macular edema (DME) is a leading cause of vision loss in developed countries.1 Prolonged hyperglycemia initiates oxidative stress and retinal hypoxia, causing an upregulation of angiogenic mediators such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2).2 These mediators have been identified to play a key role in developing DME by inducing increased vascular permeability and promoting angiogenesis, resulting in the breakdown of the blood–retinal barrier and accumulation of intraretinal fluid.2 
Initially, DME was managed through focal or grid lasers, targeting specific areas of leakage. The introduction of intravitreal anti-VEGF injections revolutionized the treatment of DME and have since become the standard of care, replacing laser therapy due to its superior efficacy in improving vision.3,4 In most eyes, anti-VEGF therapy is effective in reducing retinal thickening and improving vision. However, regular intravitreal injection intervals are necessary to maintain therapeutic efficacy. Treat-and-extend (T&E) or pro re nata (PRN) schemes are often applied, and vision usually stabilizes over the course of 2 years of treatment.5,6 Still, persistent DME is observed in more than 30% of eyes 6 months after initiating treatment with aflibercept. Among these eyes, 44% exhibit chronic persistent DME over a 2-year period.7 The increasing prevalence of diabetes underscores the significance of DME as a substantial global health concern, not only affecting patients but also placing burdens on care providers and the health care system.1 
In January 2022, faricimab (Vabysmo; Genentech, San Francisco, CA, USA), was approved by the US Food and Drug Administration and in September 2022 by the European Medicines Agency. Faricimab is a bispecific antibody that binds and inhibits VEGF-A and Ang-2, thereby targeting two important mediators of DME development. The phase II BOULEVARD study reported a benefit of simultaneous inhibition of these agents in terms of visual gain and durability.8 The phase III faricimab clinical trials YOSEMITE and RHINE showed noninferior vision gains to anti-VEGF agent aflibercept and anatomic improvements with dosing intervals of up to 16 weeks.9 Nonetheless, the outcomes observed in clinical trials may not universally reflect the effectiveness observed in patient populations within a real-world clinical setting.10 The primary objective of this study was to assess the time to retreatment and short-term anatomic and visual outcomes of faricimab following a switch from aflibercept among aflibercept treatment responders and nonresponders in the real world. 
Methods
For this retrospective, consecutive case series, patients with DME who were switched from aflibercept to faricimab between August 2023 and January 2024 at the Department of Ophthalmology at the Medical University of Vienna were identified from the electronic medical record (VIBES registry). The study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the Medical University of Vienna (EK-Nr. 2095/2018). All patients provided written informed consent for inclusion in the registry and analysis from the registry. 
Inclusion and Exclusion Criteria
Included were patients with type 1 or type 2 diabetes diagnosed with DME previously treated with aflibercept. Only eyes with at least one aflibercept injection within the past 8 months and more than one aflibercept injection in total were included. A switch to faricimab was offered to all patients and happened irrespective of the last response to aflibercept administered in a PRN regimen with a loading dose of two monthly faricimab injections, followed by a T&E regimen based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) at the discretion of the treating physician. The decision to switch was based on recent evidence indicating longer injection intervals than aflibercept.9 Other inclusion criteria were a complete clinical visit at baseline and at least two visits within 12 weeks after the first faricimab injection. Excluded were patients with other retinal diseases, severe media opacity, or a history of intravitreal steroids or vitreoretinal or cataract surgery within the last 6 months before the initial faricimab injection. 
Patients were retrospectively categorized into two groups based on their CST change 4 weeks after the last aflibercept injection into previous responding DME (rDME, CST reduction of ≥20% or CST < 250 µm) and nonresponding DME (nrDME, CST reduction <20% or CST increase). The same criteria were used to define response under faricimab treatment. 
Clinical Assessment and Imaging
Clinical and imaging data were extracted from the electronic medical record, including results of routine clinical examination, treatments, and visual acuity. Patients were seen in the diabetic eye clinic every 4 weeks after the first faricimab injection. The 6-mm × 6-mm macular optical coherence tomography (OCT) scans were obtained at every visit with a spectral domain OCT (Cirrus, Carl Zeiss Meditec, Dublin, CA, USA) during faricimab and aflibercept treatment, and swept-source OCT (Triton, Topcon, Tokyo, Japan) was used in some cases during aflibercept treatment. Automated CST measurements were obtained for every visit, with the CST boundaries set from the internal limiting membrane to the anterior boundary of the retinal pigment epithelium on both devices.11,12 
After two loading doses, patients were continued with a T&E regimen at the discretion of the treating ophthalmologist. Additionally, injection-related complications and treatment switches were assessed for every visit. 
Main and Secondary Outcomes
Main outcome was time to retreatment. Injection intervals were assessed at weeks 8 and 12. In addition, change in visual acuity and CST was analyzed and compared between the rDME and nrDME groups. 
Statistical Analysis
Mean ± standard deviation are reported for quantitative variables with approximately normal distribution, while median (range) are used otherwise. Absolute frequencies and percentages are used describing qualitative variables. 
For group comparison of patient-specific metric faricimab baseline variables (e.g., age), two-sample t-tests were applied, and for group comparison of dichotomous variables (e.g., vitrectomy), χ2 tests (or Fisher's exact tests) were calculated, whereby one eye per patient was included in the analysis. For group comparison of eye-specific metric faricimab baseline variables (e.g., visual acuity), mixed models (R-function lme, R-package nlme13) were calculated with previous DME response as the independent variable and patient ID as the random factor, using all valid observations. For group comparison of CST at week 8, a mixed model was calculated with patient ID as the random factor. The dependent variable was CST at week 8. Independent variables were CST at faricimab baseline and previous DME response (dichotomous). For group comparison of CST at week 12, a similar model was applied, but the dichotomous variable faricimab injection at week 8 (yes/no) was included as an additional independent variable. Group comparison of visual acuity at week 8 or 12, respectively, was done as described above. The differences from baseline (of visual acuity or CST, respectively, at week 8 or week 12) were estimated for each prefaricimab DME response group by mixed models with patient ID as a random factor. The difference from baseline was the dependent variable, and prefaricimab DME response was the independent variable. Statistical analyses were carried out with R 4.3.2. The significance level was set to α = 0.05. Due to the exploratory character of the study, no adjustment for multiple testing was conducted. The interpretation of the P values was exploratory. 
Results
Medical data of 70 eyes of 56 patients who received faricimab for DME from August 2023 until January 2024 with a 12-week follow-up at the Department of Ophthalmology at the Medical University of Vienna were retrospectively assessed. Eighteen eyes of 16 patients were excluded because of no prior anti-VEGF therapy (five eyes), last anti-VEGF over 8 months ago (three eyes), intravitreal corticosteroids in the past 6 months (3 eyes), history of macular hole (one eye), prior central vein occlusion (one eye), severe cataract (one eye), and incomplete clinical data, including missing OCT imaging and loss to follow-up (four eyes). 
Fifty-two eyes of 40 patients (21 female) met inclusion criteria, and patients were retrospectively divided into previous rDME and nrDME under aflibercept. Faricimab baseline variables were not significantly different between DME responder groups. Details about patient characteristics before the switch to faricimab can be found in Table 1. rDME patients received 3.9 ± 1.8 aflibercept injections in the past year, with a median aflibercept PRN interval of 6 (2–55) weeks before the switch. nrDME patients received 4.9 ± 2.3 aflibercept injections in the past year, with a median aflibercept PRN interval of 5 (4–79) weeks before the switch. Comparison of the median number of aflibercept injections in total and the past year, median aflibercept PRN interval before the switch, and mean duration of aflibercept treatment did not reveal a significant difference between rDME and nrDME groups. In the 8 months before the switch, 2 eyes received one aflibercept injection, 23 eyes received two to four aflibercept injections, and 1 eye received more than four aflibercept injections in the rDME group. In the nrDME group, 4 eyes received one aflibercept injection, 17 eyes received two to four aflibercept injections, and 5 eyes received more than four aflibercept injections in the 8 months before the switch. See Supplementary Table S1 for the results of the group comparison of previous responding DME versus nonresponding DME baseline characteristics. 
Table 1.
 
Baseline Characteristics
Table 1.
 
Baseline Characteristics
Morphology and Visual Acuity
In the rDME group, mean CST was 370 ± 99, 265 ± 55, 262 ± 53, and 288 ± 80 µm at baseline and weeks 4, 8, and 12, respectively. For the nrDME group, mean CST at the same time points was 384 ± 85, 371 ± 95, 352 ± 90, and 380 ± 129 µm. 
At week 8, mean CST for rDME was significantly lower compared to baseline (estimate [95% confidence interval (CI)]: –98 [–140 to –56], P < 0.0001), and this significant reduction persisted at week 12 (estimate [95% CI]: –74 [–122 to –27], P = 0.003). For nrDME, mean CST did not show a significant decrease of CST at either time point (week 8: estimate [95% CI]: –37 [–80 to 6], P = 0.091; week 12: –9 [–58 to 39], P = 0.70). When comparing rDME and nrDME, mean CST was significantly lower for rDME compared to nrDME (estimate [95% CI]: –77 [–123 to –30], P = 0.0051) at week 8, although this difference was not statistically significant at week 12 (estimate [95% CI]: –72 [–147 to 2], P = 0.056). 
Mean visual acuity (VA) for the rDME group was 0.29 ± 0.23, 0.23 ± 0.21, 0.19 ± 0.21, and 0.22 ± 0.28 logMAR, and in the nrDME group, mean VA was 0.42 ± 0.32, 0.44 ± 0.33, 0.34 ± 0.29, and 0.36 ± 0.29 at baseline, week 4, week 8, and week 12, respectively. 
At week 8, VA compared to faricimab baseline was significantly better for both rDME (estimate [95% CI]: –0.098 [–0.17 to –0.029], P = 0.0066) and nrDME (estimate [95% CI]: –0.072 [–0.14 to –0.004], P = 0.039). At week 12, VA was on average lower than baseline, with a statistically significant difference observed for rDME (estimate [95% CI]: –0.077 [–0.15 to –0.001], P = 0.047) but not for nrDME (estimate [95% CI]: –0.058 [–0.13, 0.017], P = 0.13). There were no significant differences in VA between rDME and nrDME at week 8 (P = 0.17) and week 12 (P = 0.32). Figure 1 shows corresponding boxplots of VA and CST for rDME and nrDME, providing a visual representation of these findings. 
Figure 1.
 
Comparison of CST and visual acuity between responding DME and nonresponding DME. The boxplots illustrate the distribution across baseline, week 4, week 8, and week 12 with outliers indicated by dots. The mean value is indicated by a cross. In the bottom of the graph, the number of eyes (n) per group is shown. The P values derived from the mixed models with the difference to baseline as the dependent variable are shown above the graph. Significant P values are bold.
Figure 1.
 
Comparison of CST and visual acuity between responding DME and nonresponding DME. The boxplots illustrate the distribution across baseline, week 4, week 8, and week 12 with outliers indicated by dots. The mean value is indicated by a cross. In the bottom of the graph, the number of eyes (n) per group is shown. The P values derived from the mixed models with the difference to baseline as the dependent variable are shown above the graph. Significant P values are bold.
Faricimab Response
Week 4: Among rDME, 15 eyes (58%, [CST µm minimum, maximum 188, 312]) responded to faricimab treatment with a CST decrease of over 20% or a CST under 250 µm. None of these eyes exhibited a CST increase of more than 20%. However, 11 eyes (42%, [252, 418]) showed CST changes within the range of ±20%. For nrDME, five eyes (22%, [239, 354]) were responders to faricimab treatment. Three eyes (13%, [391, 666]) demonstrated a CST increase of more than 20%, while 15 eyes (65%, [275, 519]) showed a ±20% CST change. Visit data for three eyes were missing at week 4. 
In total, 20 of 49 eyes (41%) showed a CST reduction over 20% or a CST under 250 µm; in 26 eyes (53%), CST change was ±20%; and in 3 eyes (6%), a CST increase of over 20% was observed. 
Week 8: For rDME, 19 eyes (73%, [184, 345]) responded to faricimab treatment, and 7 eyes (27%, [257, 408]) showed CST change of ±20%. No eyes showed an increase of more than 20%. Among nrDME, 6 eyes (26%, [194, 369]) responded to faricimab treatment, 3 eyes (13%, [359, 428]) had an increase of over 20%, and 14 eyes (61%, [268, 605]) showed a ±20% CST change. Visit data for three eyes were missing at week 8. 
In total, 25 of 49 eyes (51%) had either a CST reduction over 20% or a CST thickness under 250 µm. In 21 eyes (43%). CST change was ±20%, while in three eyes (6%), a CST increase of over 20% was observed. 
Week 12: In rDME, 14 eyes (54%, [182, 312]) responded to faricimab, 12 eyes (46%, [259, 533]) showed a CST change of ±20%, and no eyes exhibited an increase of over 20%. For nrDME, 6 eyes (25%, [207, 289]) responded to faricimab, 12 eyes (50%, [260, 512]) showed a CST change of ±20%, and 6 eyes (25%, [397, 725]) demonstrated a CST increase of more than 20%. Visit data for two eyes were missing at week 12. Altogether, 20 of 50 eyes (40%) responded positively to faricimab treatment. In 24 eyes (48%), CST change fell within the range of ±20%, while in 6 eyes (12%), a CST increase of over 20% was seen. 
Figure 2 visually represents the response to faricimab treatment per week using pie charts. 
Figure 2.
 
Pie charts of faricimab treatment response per week, DME responder group, and in total. Percentages of eyes with CST reduction >20% or CST<250 µm, CST ±20%, or CST increase >20% are color-coded and specified.
Figure 2.
 
Pie charts of faricimab treatment response per week, DME responder group, and in total. Percentages of eyes with CST reduction >20% or CST<250 µm, CST ±20%, or CST increase >20% are color-coded and specified.
Treatment Interval
All patients received two monthly loading doses followed by a T&E regimen as decided by the treating physician. 
Among rDME, 19 eyes (73%) were extended after the loading dose and received a third injection at week 12. Five eyes (19%) received an injection at week 8 and were then extended to an 8-week interval. Only one eye (4%) received injections at both weeks 8 and 12. In the nrDME group, eight eyes (31%) were extended after the loading dose and received a third injection at week 12. Five eyes (19%) received an injection at week 8 and were extended thereafter to an 8-week interval. Eleven eyes (42%) were not extendable and received injections at weeks 8 and 12. 
At the end of week 12, in the rDME group, 19 eyes (73%) reached an extended interval of 8 weeks or longer. Thereof, 5 eyes (19%) were at 8-week injection intervals, 1 eye was at a 10-week injection interval, and 13 eyes (50%) were at 12-week injection intervals. One eye (4%) was at a 6-week interval, and five eyes (19%) were at a 4-week interval. In one eye (4%), faricimab therapy was stopped due to insufficient response. 
In the nrDME group, 12 eyes (47%) could be extended to an interval of 8 weeks or longer. Thereof, eight eyes (31%) were at an 8-week interval, two eyes (8%) were at a 10-week interval, and two eyes (8%) were at a 12-week interval. One eye (4%) was at a 6-week interval, and 11 eyes (42%) were at a 4-week interval. In two eyes, therapy with faricimab was stopped due to unresponsiveness to treatment. 
In the total cohort, 31 eyes (60%) reached an extended interval of 8 weeks or longer. Thereof, 13 eyes (25%) were at an 8-week interval, 3 eyes (6%) were at a 10-week interval, and 15 eyes (29%) were at a 12-week injection interval. Two eyes (2%) were at a 6-week interval, and 16 eyes (31%) were at a 4-week interval. In three eyes (6%), faricimab therapy was stopped. A graphical illustration of treatment intervals at week 12 is shown in Figure 3
Figure 3.
 
Barplot of faricimab treatment intervals (in weeks) among responding DME (n = 26 eyes), nonresponding DME (n = 26 eyes), and in total (n = 52 eyes). stop, faricimab stop.
Figure 3.
 
Barplot of faricimab treatment intervals (in weeks) among responding DME (n = 26 eyes), nonresponding DME (n = 26 eyes), and in total (n = 52 eyes). stop, faricimab stop.
None of our patients received a “rescue” treatment, meaning that the assigned treatment interval at week 12 was not shortened before the end of the assigned T&E time point. 
Injection-Related Complications
Following the first loading dose, vitreous hemorrhage occurred in one eye, which fully resolved within 4 weeks, allowing for the second loading dose within the predetermined interval. No other injection-related complications were observed within this study population. 
Discussion
We evaluated the short-term outcomes of a switch from aflibercept to faricimab in the treatment of DME. Previous responding DME eyes before the switch to faricimab (CST reduction ≥20% or CST < 250 µm) had a higher CST reduction under faricimab than previous nonresponding DME eyes (CST reduction <20% or CST increase). Time to retreatment could be extended in 73% (n = 19) of previous responding DME to 8 weeks or longer and in 47% (n = 12) of previous nonresponding DME after 12 weeks. 
Responders and Nonresponders
Currently, there is no standardized definition for response to anti-VEGF therapy in DME. One method to assess response is by evaluating the anatomic changes after treatment using OCT. Treatment decisions guided by CST measurements have proven to be clinically useful. Most commonly, an increase or unchanged CST after anti-VEGF treatment is considered treatment-resistant or persistent DME.14 However, there is no consensus on the definition of CST improvement thresholds across current literature. Some studies report posttreatment CST values between 250 and 350 µm as improvements,7,15,16 while others consider a fixed-volume reduction such as 50 µm a success.17,18 Additionally, a percentage reduction in CST from baseline, with percentages varying from 10% to 25%, has also been reported.7,1922 In our study, we used a combination of criteria with a defined treatment response as either a ≥20% reduction or a final CST thickness of <250 µm to account for a return to normal retinal thickness based on Bressler et al.7 
Central Subfield Thickness and Visual Acuity
Changes in CST serve as an effective indicator for evaluating treatment response and demonstrate real-world applicability in guiding treatment decisions. While an anatomic response to anti-VEGF or anti-VEGF/Ang-2 may be good, there is only a moderate correlation between macular thickness and visual acuity.23 
Recent real-world studies in previously treated DME eyes using faricimab showed that there is no consensus regarding loading doses in routine clinical practice. 
Rush et al.24,25 reported a mean CST reduction from 400 to 340 µm after three faricimab injections within 4 months, which maintained at 341 µm after 1 year. Baseline VA improved from 0.60 to 0.50 logMAR after 4 months and to 0.47 logMAR after 1 year. Quah et al.26 reported a CST reduction from 493 ± 133 µm to 389 ± 131 µm 4 weeks after three monthly faricimab injections, with VA improving from 60.8 to 64.3 letters. However, the prior response to DME treatment was not reported. Ohara et al.27 reported a CST reduction from 474 ± 220 µm to 381 ± 220 µm after 4 months PRN, with 55.6% showing a CST reduction of over 20%. Mean VA improved from 0.23 ± 0.28 logMAR to 0.19 ± 0.23 logMAR at week 16. In comparison, mean CST reduction in our nrDME group was less pronounced, with a mean CST reduction from 384 ± 85 µm at baseline to 380 ± 129 µm at week 12, with 25% of our patients achieving a CST reduction of ≥20% or a final CST <250 µm. 
Durrani et al.,28 without indicating a standardized loading dose, reported a CST decrease from 380 ± 158 µm to 328 ± 149 µm after three faricimab injections, with no significant VA change with 0.40 ± 0.30 to 0.38 ± 0.27 logMAR. Similar to these findings, VA changes in our nrDME group were not significant, with a mean VA of 0.42 ± 0.32 at baseline and 0.36 ± 0.29 logMAR at week 12. 
In contrast to previous studies, our analysis included DME eyes that showed a positive response to previous aflibercept treatment and compared them with eyes that were not responsive.2430 In a study by Pichi et al.,31 the cohort was categorized into “good” and “bad” visual and anatomic responders. Unlike our study, which applied a strict threshold of ≥20% CST reduction or a CST under 250 µm, Pichi et al.31 defined anatomic response based on any reduction in macular edema. Additionally, they classified groups based on the response at the baseline visit at the time of DME diagnosis rather than following the last aflibercept treatment, as we did in our analysis. In their study, patients without a prior anatomic response showed significant CST improvement, with a mean CST of 305.5 µm after 6 months. Conversely, good anatomic responders had a mean CST of 376.8 µm and exhibited minimal CST improvement. 
In our study, after 12 weeks, 54% of previous DME responders showed a good morphologic response to faricimab treatment with no reported CST increase of over 20%. CST was lower in the rDME group compared to nrDME, which was statistically significant at week 8. Both groups showed a CST reduction compared to baseline, but the difference was only statistically significant in the rDME group. Interestingly, lowest CST was reached at week 8 for both of our patient groups (rDME: 262 µm; nrDME: 352 µm). In contrast to nrDME, VA change was significant from 0.29 ± 0.23 to 0.22 ± 0.28 logMAR at week 12 in the rDME group. VA did not differ significantly between our two study groups at any time point. 
While two different OCT devices were used during aflibercept treatment, potential variability in CST measurements can be considered negligible as both devices’ segmentations are almost equivalent (correlation coefficients from 0.98–0.99, internal data from our OCT comparison study of the Vienna Reading Center). 
Furthermore, prior vitrectomy can impact the efficacy and average half-life of anti-VEGF therapy, as demonstrated by Jung et al.32 However, when excluding the three eyes with prior vitrectomy, similar statistical results with no change in test outcomes were revealed (results not shown). 
Treatment Interval
Before starting with faricimab, patients were treated with aflibercept in a PRN regimen without statistically significant differences of injection intervals or total number of previous injections between rDME and nrDME eyes. The T&E approach in DME is based on an individual dosing regimen that depends on disease activity. An insufficient response to anti-VEGF treatment may result from an inadequate dosing frequency or difficulties adhering to regular monthly visits.1,33 Previously treated DME patients at the Department of Ophthalmology at the Medical University of Vienna switched to faricimab are treated with two loading doses, followed by a gradual extension of treatment intervals by 4 weeks based on CST and BCVA at the discretion of the treating physician. 
The phase III YOSEMITE and RHINE trials reported that by year 1, 72% of patients in the faricimab T&E group achieved treatment intervals of 12 weeks or longer, with 52% reaching 16-week treatment intervals.9 Preliminary 2-year data from YOSEMITE/RHINE showed that patients treated with faricimab reached better morphologic results (CST <325 µm) earlier and with fewer injections than with aflibercept.34 
In the past year, real-world outcomes for faricimab treatment have shown a similar trend compared to the phase III studies. Rush25 reported injection intervals of 8 weeks or longer and resolved DME in 39% of patients after 12 months of treatment. Ohara et al.27 reported a 12-week treatment interval in 44% of 18 patients with persistent DME treated with a PRN faricimab protocol. Durrani et al.28 reported that after a mean duration of 3.2 ± 1.1 months, 23% were in ≥8-week T&E intervals, with 1.4% in a 12-week interval. In comparison, 47% of our nrDME eyes reached an extended interval of 8 weeks or longer after 12 weeks and 8% a 12-week interval. Conversely, 73% of rDME eyes were in treatment intervals of 8 weeks or longer, with 50% in a 12-week interval. 
Eyes previously responsive to anti-VEGF treatment showed a quicker response to faricimab treatment, with most eyes being extended after the loading dose. Seventy-three percent of DME eyes previously responding to treatment responded well after the faricimab loading dose and could subsequently be extended. In contrast, eyes with prior inadequate anti-VEGF response required more injections before they could be extended. 
To our knowledge, there are currently no published real-world data available comparing eyes with previously responding and nonresponding DME under aflibercept who were switched to faricimab. This study's limitations include its retrospective study design and a limited follow-up period. While clinician heterogeneity and variability in treatment strategies are potential concerns, the use of a standardized clinical procedure and imaging protocols ensures comparability. Another limitation is the variability in the number and duration of prior aflibercept treatments, although this difference was not statistically significant between the two groups. Nonetheless, the consecutive inclusion of patients is a notable strength of this study. 
Our findings contribute to the current literature on faricimab in the treatment of DME and extend it by comparing rDME and nrDME in a real-world setting applicable to the clinical routine. 
Conclusions
Our study showed that following a switch to faricimab, treatment intervals of DME responders under aflibercept could be extended earlier and longer compared to nonresponders. However, the improvement in visual acuity was not significantly different between the two groups. Morphologically, previous DME responders showed a superior treatment response after a switch to faricimab, evidenced by lower CST levels, compared to previous nonresponding DME. 
Acknowledgments
Abstract of the preliminary data from this study was presented at the annual meeting of the “Österreichische Gesellschaft für Ophthalmologie” in May 2024. 
Disclosure: K.L. Huber, None; H. Stino, None; I. Steiner, None; P. Fuchs, None; F. Goldbach, None; J. Mai, Apellis (C), Boehringer Ingelheim (C), Roche (C); B.S. Gerendas, Roche (C), Zeiss (C), Abbvie (C), Bayer (C); K. Kriechbaum, None; U. Schmidt-Erfurth, Apellis (C, F), AbbVie (C, F), Alcon (F), Bayer (C), Medscape (C), Allergan (C), Roche (C), Boehringer (C), Aviceda (C), Annexon (C), Topcon (C), Alkeus (C), Genentech (C), Kodiak(C), Novartis(C), RetInSight (C), Apellis Pharmaceuticals (C); A. Pollreisz, Allergan (C), Bayer (C), Roche (C), Oertli Instruments (C) 
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Figure 1.
 
Comparison of CST and visual acuity between responding DME and nonresponding DME. The boxplots illustrate the distribution across baseline, week 4, week 8, and week 12 with outliers indicated by dots. The mean value is indicated by a cross. In the bottom of the graph, the number of eyes (n) per group is shown. The P values derived from the mixed models with the difference to baseline as the dependent variable are shown above the graph. Significant P values are bold.
Figure 1.
 
Comparison of CST and visual acuity between responding DME and nonresponding DME. The boxplots illustrate the distribution across baseline, week 4, week 8, and week 12 with outliers indicated by dots. The mean value is indicated by a cross. In the bottom of the graph, the number of eyes (n) per group is shown. The P values derived from the mixed models with the difference to baseline as the dependent variable are shown above the graph. Significant P values are bold.
Figure 2.
 
Pie charts of faricimab treatment response per week, DME responder group, and in total. Percentages of eyes with CST reduction >20% or CST<250 µm, CST ±20%, or CST increase >20% are color-coded and specified.
Figure 2.
 
Pie charts of faricimab treatment response per week, DME responder group, and in total. Percentages of eyes with CST reduction >20% or CST<250 µm, CST ±20%, or CST increase >20% are color-coded and specified.
Figure 3.
 
Barplot of faricimab treatment intervals (in weeks) among responding DME (n = 26 eyes), nonresponding DME (n = 26 eyes), and in total (n = 52 eyes). stop, faricimab stop.
Figure 3.
 
Barplot of faricimab treatment intervals (in weeks) among responding DME (n = 26 eyes), nonresponding DME (n = 26 eyes), and in total (n = 52 eyes). stop, faricimab stop.
Table 1.
 
Baseline Characteristics
Table 1.
 
Baseline Characteristics
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