Short-term response to anti-vegf as indicator of visual prognosis in refractory age-related macular degeneration


Short-term response to anti-vegf as indicator of visual prognosis in refractory age-related macular degeneration

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ABSTRACT BACKGROUND Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections.


Their short-term response between injections was investigated for extent and visual prognosis. SUBJECTS/METHODS Monocentric retrospective observational study. 45 eyes from 41 patients with


refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid


profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric


measurements performed by an automated algorithm based on artificial intelligence. RESULTS A significant improvement was found at week 1 in terms of CRT (_p_ < 0.0001), intraretinal (IRF)


(_p_ = 0.007), subretinal fluid (SRF) (_p_ < 0.0001), and pigment epithelium detachment (PED) volume (_p_ < 0.0001). Volumetric fluid measures revealed a >50% reduction at week 1


for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF + SRF) (_p_ = 0.003), larger PED (_p_ = 0.007),


lower visual acuity (_p_ = 0.004) and less anatomic changes at treatment initiation (_p_ < 0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later


was significantly worse with weaker short-term responsiveness (_p_ = 0.005), with the presence of atrophy (_p_ = 0.01) and larger PED volumes (_p_ = 0.002). CONCLUSIONS Incomplete responders


to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated


with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis. SIMILAR CONTENT BEING VIEWED BY OTHERS IMPACT OF MACULAR FLUID VOLUME


FLUCTUATIONS ON VISUAL ACUITY DURING ANTI-VEGF THERAPY IN EYES WITH NAMD Article Open access 07 January 2021 PERSONALIZED TREATMENT SUPPORTED BY AUTOMATED QUANTITATIVE FLUID ANALYSIS IN


ACTIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (NAMD)—A PHASE III, PROSPECTIVE, MULTICENTRE, RANDOMIZED STUDY: DESIGN AND METHODS Article Open access 05 July 2022 THE ASSOCIATION


BETWEEN OPTICAL DENSITY RATIO OF INTRARETINAL FLUID AND VISUAL ACUITY IN NEOVASCULAR AGE RELATED MACULAR DEGENERATION AFTER 36 MONTHS OF FOLLOW UP Article 15 April 2025 INTRODUCTION Since


the advent of anti-VEGF treatment, the visual prognosis of patients with neovascular age-related macular degeneration (nAMD) has changed dramatically [1,2,3]. These good results can be


achieved at the cost of regular and timely treatment. However, some eyes remain incomplete responders in that exudative fluid may persist despite maximal monthly treatment. These cases have


been referred to as refractory patients, incomplete responders, or resistant to anti-VEGF [4, 5]. Fluid dynamics following an anti-VEGF intravitreal injection in incomplete responders have


been studied [6, 7]. While most cases show a good short-term response with quick relapse, a proportion of patients show persistent fluid that is truly refractory [7]. Although untreated or


undertreated exudative activity is a reason for eventual visual acuity (VA) loss in nAMD, the visual prognosis of incomplete responders despite maximal treatment is less clear. Some studies


have reported relatively good retention of VA in these patients [8, 9]. Furthermore, recently several studies investigated whether some subretinal fluid (SRF) could be actively tolerated


without visual loss [10,11,12,13]. We hypothesized that the short-term response to anti-VEGF as identified by fluid measurements in between injections may be a relevant factor for visual


prognosis. Thus, the goal of the present study was to investigate the fluid dynamics in incomplete responders to anti-VEGF, with respect to the VA prognosis. In addition, we aimed to


pinpoint associated clinical or imaging factors as a mean to better understand the pathogenesis. METHODS This study was performed as a retrospective chart and optical coherence tomography


(OCT) imaging review, in the medical retina department of the University Eye Hospital Jules Gonin, Lausanne, Switzerland. The study was approved by the Swiss Federal Department of Health for


retrospective data analysis (Commission cantonale d’éthique CER-VD protocol number 2017-02175) and was performed in accordance with the ethical standards of the Declaration of Helsinki. The


need for written informed consent was waived by the ethics committee. We identified a consecutive series of eyes with nAMD which underwent an intermediate visit at 1 week after injection


due to their incomplete response to anti-VEGF, defined as presence of intraretinal fluid (IRF) and/or SRF at each monitoring visit associated with the injection dates, and despite monthly


anti-VEGF injections. This approach constituted the routine clinical practice for patients in whom incomplete response was found for 6 months or more, after a minimum of 12 months of


anti-VEGF treatment. In addition, the eye had to be on the same anti-VEGF agent (ranibizumab or aflibercept) for at least 6 months. Before this time frame, switching between anti-VEGF drugs


was allowed to the investigators’ discretion. The period screened for these inclusion criteria was from November 2014 to January 2017. Exclusion criteria were insufficient quality of


spectral domain (SD)-OCT images, any adjuvant treatment during the preceding year, any confounding retinopathy, ongoing topical treatment with prostaglandins, and any intraocular surgery


during the preceding 6 months. The routine clinical treatment attitude was a no tolerance strategy for fluid, translating into ongoing monthly treatment as long as fluid remained present. In


case of successful fluid suppression, treatment intervals were prolonged in 2 weekly steps. The routine ophthalmic visit included medical and ophthalmic history, best corrected VA (BCVA) on


an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, intraocular pressure, and slit-lamp and dilated fundus examination. Patients underwent an SD-OCT examination on the Heidelberg


Spectralis OCT (macular cube 6 mm, 49 lines; Heidelberg Engineering, Heidelberg, Germany) at each visit. For the present study, the date of the intermediate visit 1 week after an anti-VEGF


injection determined the previous visit just before the anti-VEGF injection as study-baseline. This baseline visit, the visit 1 week after the injection, and the following visit at 1 month


post-injection were analyzed and the following parameters collected: age, sex, eye, duration of previous anti-VEGF treatment, current anti-VEGF agent used, BCVA (routinely measured on ETDRS


chart), date of the preceding injection, central retinal thickness (CRT), the maximal distance from internal limiting membrane to the retinal pigment epithelium (RPE) on SD-OCT, and the


maximum elevation of RPE from Bruch’s membrane. The A-scan location of the latter two parameters was determined on baseline images and measured on identical A-scans using the follow-up mode


for the succeeding two timepoints. In addition, the OCT images from baseline and 1 week later were qualitatively compared by the same investigator (SK, blinded to the algorithmic evaluation)


and assigned to one of the following response categories: good, defined as demonstrating IRF and SRF absorption of more than half the baseline volume; moderate, defined as demonstrating


visible fluid reduction but not more than 50%, and poor, defined as demonstrating no clear change in fluid amounts (less than 10%). Additional information extracted from baseline OCT


included the presence or absence of vitreomacular adherence or traction and the thickness of the subfoveal choroid measured on enhanced depth imaging. The same OCT images were exported from


the Spectralis device and analyzed by an automated algorithm (using a convolutional neural network and reinforced by layer segmentation), developed by the group RetinAI for identification


and quantification of IRF and SRF, as well as the RPE elevation from Bruch’s membrane. The details of the algorithm are published elsewhere [14]. In brief, the algorithm was tested in a


specific set of OCT volumes and showed a satisfying performance for all three compartments. In particular, the volumetric correlation between human expert and algorithm measurements were


high (correlation coefficient of 0.99 for both IRF and SRF, and 0.91 for the sub-RPE space.9 This algorithm performed the volumetric measurements of fluid and RPE elevation in this study.


The presence or absence of atrophy was determined on fundus autofluorescence imaging at study baseline, in doubtful cases in combination with OCT. The presence or absence of fibrosis was


determined on fundus color imaging. Furthermore, the functional and structural response after treatment initiation in the past was evaluated, one month after three monthly loading doses


(best available visual acuity before treatment and after loading dose, CRT before and after loading dose, presence or absence of fluid after loading dose). Angiography was routinely


performed when an incomplete response to treatment was found, including fluorescein and indocyanine green angiography (ICGA) on the Heidelberg Retinograph (Heidelberg Engineering).


Information extracted from the last available fluorescein and ICGA included the neovascularization type (occult/type 1, classic/type 2, or retinal angiomatous proliferation/type 3), presence


of aneurysmal choroidal changes (polypoidal vasculopathy), presence and diameter of a choroidal feeder vessel on early ICGA frames, and presence of any inflammatory signs (disc


hyperfluorescence and/or diffuse exudation from the RPE). The measured blood pressure was recorded for both systolic and diastolic values. For statistical analysis, a Microsoft Excel 2010


spreadsheet (Microsoft, Redmond, WA) and JMP software for Windows (version 8.0.1, SAS Institute, Cary, NC) were used. Besides descriptive statistics, the t-test was used for analysis of


paired parameters (changes over time). An association analysis was performed for two outcome measures: the proportion of fluid (IRF and SRF) remaining present at week 1 as compared to


baseline, and the absolute volume of the same remaining fluid. To identify factors related to the outcome measures, we used logistic regression for categorical variables, and Pearson’s test


for continuous variables. For factors with _p_ ≤ 0.2 in the univariate analysis, a step-by-step multivariate analysis was performed to determine independent variables. For the statistical


results, a two-tailed _p_-value of 0.05 or less was considered statistically significant. RESULTS A total of 45 eyes (24 right eyes, 21 left eyes) of 41 patients (29 females, 12 males, mean


age 78 ± 6 years) were identified and included into the analysis. The number of injections preceding the study baseline was a mean of 27 ± 15 injections, distributed over a mean 32 ± 19


months. The mean interval between two injections within the study period was 31 ± 3 days just before baseline and 30 ± 4 days between baseline and the next injection. The anti-VEGF drug used


during the 6 months preceding baseline and directly thereafter was ranibizumab in 22 eyes and aflibercept in 23 eyes. At anti-VEGF treatment initiation, visual acuity improved after the


three monthly loading doses from a mean 65.2 ± 14.8 to 71.4 ± 14.8 ETDRS letters, and central retinal thickness decreased form 396 ± 146 um to 308 ± 101 µm. However, after loading dose


residual fluid was still present in 67% of the eyes (IRF and SRF in 16%, IRF only in 4%, SRF only in 47%). The short term responsiveness results between monthly injections, this is one week


after baseline, are summarized in Table 1. Structural outcome measures all showed a significant change one week after injection as compared to baseline. These significant changes were all


lost at 1 month from the preceding injection (except the manual height measures which still suggested a reduction for the neuroretinal fluid + SRF (_p_ = 0.0005), and for PED (_p_ = 0.01)).


The time interval from the preceding injections was not significantly different at the 1-month visit as compared to study baseline. Identifying eyes with the presence of IRF and SRF


separately, defined as a volume of >10 µm3 at baseline, revealed 15 eyes with IRF (mean volume 222 ± 231 µm3) and 33 eyes with SRF (mean volume 238 ± 272 µm3), with 3 patients presenting


both IRF and SRF. Both of these groups showed a mean reduction of fluid of 69% (range 0–100%). Figure 1A, B displays graphically the responsiveness between injections, grouped according to


the subtype of fluid present, revealing that approximately two thirds of eyes with IRF or SRF respectively show 50% or more fluid reduction between injections. However, much less change was


observed for PED, with only a 12% mean volume reduction at 1 week, although approximately one-quarter showed short-term volume changes between 20 and 55% (Fig. 1C). As the definition of


incomplete responders was based on the presence of IRF and/or SRF at each monthly visit, the sum of both was also analyzed (_n_ = 45 eyes). The response distribution at 1 week revealed


combined IRF + SRF volume reduction of ≥80%, ≥70%, ≥50%, ≥10%, in 49%, 58%, 76%, and 89% of eyes, respectively, However, in real-world settings, algorithmic fluid volume measures are not


routinely available in clinics. Thus, we also categorized patients according to the clinical appreciation of OCT changes. This approach resulted in the following distribution: 44% were


considered good responders (estimated more than 50% fluid resolution), 40% moderate responders (estimated ≤50% resolution but >10%), and 16% non-responders (estimated ≤10%). Examples can


be found in the Supplementary Figure. The responsiveness of exudative fluid (sum of IRF and SRF) was analyzed for its association with imaging factors. The distribution of imaging factors is


listed in Table 2. The association with the short-term responsiveness of exudative fluid (IRF + SRF) was analyzed in univariate analysis. This revealed a significant negative correlation


with baseline fluid volume of IRF + SRF (_r_ = −0.43; _p_ = 0.003), as well as PED (_r_ = −0.40; _p_ = 0.007). A weak, but statistically significant association was also found between


baseline VA and short-term responsiveness (_r_ = 0.09; _p_ = 0.004), this is the better the vision the better the responsiveness. Finally, higher reduction in CRT (negative value) at


initiation of anti-VEGF treatment was linked to less responsiveness of refractory fluid (_r_ = 0.14; _p_ < 0.0001). No other factor was significantly associated. Notably, there was no


association with polypoidal vasculopathy or traction. Furthermore, the relevance of the responsiveness in terms of visual prognosis was investigated. Follow-up after the study period was


available for an additional 1, 2, 3, 4, and 5 years for 42, 38, 35, 32, and 30 eyes, respectively. The available VA at yearly time points since evaluation of the short-term responsiveness


showed a mean change of −2.0 ETDRS letters (standard deviation [SD] 8.0, _n_ = 42), −5.4 letters (SD 9.9, _n_ = 38), −7.3 (SD 10.0, _n_ = 35), −7.3 (SD 12.1, _n_ = 32), −8.9 (SD 12.8, _n_ = 


30), after 1, 2, 3, 4, and 5 years, respectively. The correlation analysis of the short-term responsiveness of exudative fluid with VA changes over the following 5 years revealed a


significant correlation at years 4 and 5 (correlation factors 0.35 (_p_ = 0.02) and 0.58 (_p_ < 0.0001), respectively) (Table 3); the stronger the responsiveness between injections (in


fluid percentage of IRF + SRF), the better the visual prognosis in the long run. The corresponding results after 1–3 years were not significant. Figure 2 shows the visual change over the


follow-up duration from study baseline, according to the subgroups of at least 70% responsiveness of the refractory exudative fluid at 1 week after injection versus those with less


responsiveness. While those with more than 70% responsiveness lost only one ETDRS line (5 letters) over 5 years, the less responsive group lost more than 3 ETDRS lines (>15 letters).


Exploring the correlation separately for those with IRF versus those with SRF confirmed this result for the group with SRF (_n_ = 33) after 5 years of follow-up (_r_ = 0.61, _p_ = 0.0002).


However, while the IRF group showed the same trend (_r_ = 0.21) the group size with only 15 eyes was underpowered to be significant (_p_ = 0.15). The visual results after 5 years of


follow-up showed significant correlations in univariate analysis with other factors as well (Table 3). A negative correlation was found for the volume of exudative fluid at study baseline


(_r_ = −0.30; _p_ = 0.045), for residual fluid volume at week 1 (_r_ = −0.31; _p_ = 0.04), for baseline PED volume (_r_ = −0.51; _p_ = 0.0003), for presence of atrophy at baseline (_p_ = 


0.04). VA was also correlated with the loss of vision at year 5 (_r_ = 0.36; _p_ < 0.0001), meaning the better the VA, the more loss over 5 years. To determine their independent


contribution, multivariate analysis with these significant factors was performed. The final model was statistically significant (_p_ = 0.004), including the responsiveness of exudative fluid


(_p_ = 0.005), baseline PED volume (_p_ = 0.002), and the presence of atrophy (_p_ = 0.01) (Table 3). DISCUSSION Refractory nAMD, which could better be called incomplete responders to


anti-VEGF, shows - according to this study – a significant response in between monthly anti-VEGF injections, at least in a large proportion (approximately two thirds) of cases. However, a


smaller proportion of cases show no relevant short-term response. Associated risk factors were larger fluid amounts and larger PED, lower visual acuity and less central retinal thickness


changes at treatment initiation. Furthermore, the study found that the degree of response between the monthly injections was relevant for long-term visual prognosis, identifiable after 4 and


5 years as greater visual loss in cases with poorer short-term response. These findings appear plausible: the more fluid and the longer it lasts, the worse the outcome. This was the case


for the sum of IRF and SRF as well as for SRF alone, in spite of a very aggressive treatment attitude of no fluid tolerance. The numbers for IRF alone were too small for a meaningful


conclusion. Additional factors for visual prognosis were the presence of atrophy and larger PED volumes. Initial VA was found to be correlated with the VA loss after 5 years, with more loss


for better initial VA. This comes to no surprise because of the “ceiling effect” of anti-VEGF treatment: eyes with better VAs have less to gain and more to lose compared to eyes with poorer


VAs. Insufficient anti-VEGF response in nAMD with residual fluid despite maximal treatment is not a rare event, reported in up to 51% with fluid present (including IRF, SRF or PED) in the


monthly ranibizumab treatment arm in the CATT study [15]. With respect to IRF and SRF alone, this proportion can be estimated as 48% and 34% for IRF and 33% and 25% for SRF according to


monthly treatment arms with ranibizumab and aflibercept, respectively [16]. In our own prospective treatment series with ranibizumab, we found that approximately 16% of eyes still needed


monthly treatment after 2 years of customized retreatment (observe-and-plan regimen), based on the presence of IRF or SRF [17]. So far, there is no consensus regarding the terminology and


definition of cases with incomplete response to anti-VEGF. However, the presence of IRF and (recurrent) SRF on OCT has become a generally accepted indication for further treatment. Thus, we


opted for this simple definition: that the presence of fluid despite maximal monthly treatment should be considered an incomplete response [4, 15]. The advantage of this definition goes


along with an inhomogeneity in terms of short-term response in between injections, as shown in this study, and potentially with different pathophysiological backgrounds. Although a


significant short-term response has previously been shown to occur already after 1 week as identified on CRT measurements [6], our recent study using a volumetric algorithm to determine


precise fluid volumes showed important variability between cases in terms of the degree of response [7], consistent with the findings of the present study. To date, the short-term


responsiveness in between injections has got little attention, and no clinical biomarkers in association have been described. Visual function is the final purpose of eye healthcare. In a


previous study, we reported surprisingly good visual outcomes over 3 years of (at least initially) refractory cases [8]. A slight disadvantage was seen if the refractory fluid included


intraretinal cystoid spaces. However, these cases were investigated during their initial 3 years of treatment, contrasting with the present study which investigated cases during their


follow-up treatment, according to the timepoint of short-term evaluation. They already had a mean preceding treatment period of 32 ± 19 months. Although the two studies are not directly


comparable, it is intriguing that the different prognostic value of the short-term response between monthly injections in this study was seen late, after 4–5 years of further follow-up.


Although quite late, this major difference is significant for patients’ lives, as the means differ by 15 letters (3 ETDRS lines) (Fig. 2). Thus, the visual consequences of fluid exudation


are probably a product of several factors, including chronicity, quantity, location, and possibly its composition, inducing slow degenerative changes, leading ultimately to visual loss.


However, long-term studies are not often available, with most studies being limited to 2 years [10, 13, 18]. We found only one small report with results at 5 years, suggesting good visual


outcome despite subretinal fluid in 9 cases [9]. Not surprisingly, presence of atrophy and PED volume were also linked to worse visual prognosis at 4 and 5 years. In addition to the evidence


of the more deleterious effect of chronic non-responsive fluid, the dynamic curve of fluid amounts in between monthly anti-VEGF injections might reflect different pathogenic components of


the fluid. The responsive part is visibly VEGF-dependent, while the residual amount of fluid which never disappears might be of different origin, being truly anti-VEGF refractory in its more


restricted sense. We recently described a higher concentration of inflammatory biomarkers in aqueous humor in those with incomplete anti-VEGF response, as compared with normal responders


[5]. In this context, it is interesting to consider the genetic background of AMD, which strongly implies the complement cascade [19]. Recently, a broad discussion about the importance of


IRF versus SRF has suggested that persistent SRF might not be as harmful as IRF. This is based on the observation that mean VA is lower in the presence of IRF than in the presence of SRF,


both at baseline and follow-up [3, 11, 15]. However, the comparisons do not consider the chronicity of presence of fluid but only their presence or absence at individual time points. The


prospective FLUID trial was performed, allowing to actively tolerate up to 200 µm SRF if not responsive, and to extend treatment intervals in these cases [10]. With amazingly little effect


on mean injection numbers, there was no significant visual difference between the relaxed and intensive (no tolerance) treatment arms, suggesting that SRF could be tolerated. However, a more


recent post-hoc analysis of the same study showed a negative correlation between SRF volumes and visual outcomes [12]. Indeed, the precision of fluid volumetrics may help identify the


visual consequences earlier in the time course. Finally, fluid fluctuations have been reported to be more deleterious to visual function than small but stable amounts of fluid [20]. This may


be linked to relative undertreatment. Our report seemingly contradicts this, although the study type differs significantly. While the reports of deleterious fluid fluctuation were based on


recurrences under reduced treatment frequency, therefore possibly under-treatment, our study compared the treatment fluctuations under maximal monthly treatment. The lower treatment effect


in our study shows as anti-VEGF resistant fluid which chronically stagnates (less fluctuations), ultimately leading to visual loss. Therefore, it may well be that both the completely


non-responsive part of fluid and the intermittently undertreated but otherwise anti-VEGF-sensitive fluid might have similar negative effects in the long run. A few weaknesses of this study


need to be acknowledged. Besides the inherent weaknesses of a retrospective study and the limited size of the study sample, the clinical decision might have influenced the selection of


patients in whom an intermediate visit at 1 week was performed, thus possibly influencing the selection of eyes for inclusion in this study. Furthermore, no subgroup analysis was performed


to account for potential difference due to drug type (ranibizumab or aflibercept). Indeed, as the drug could be switched at the treating physician’s discretion, it would have been difficult,


if not impossible to create subgroups according to the anti-VEGF molecule. However, as the difference between the duration of effect of both drugs is mild [21], it appears unlikely that


this would impact the study results. In addition, the numbers of patients with intraretinal fluid did not allow a meaningful separate analysis of this subgroup. In conclusion, while most


incomplete responders to anti-VEGF showed a good short-term response to treatment, the evaluation of the short-term response between monthly injections may be of prognostic value: the more


IRF and SRF is present (under the curve) over the month between injections, the poorer the visual prognosis over the following 5 years. Major fluid volumes with poor short-term response


might need adjuvant treatment. However, further studies are needed to determine the nature of an adequate adjuvant treatment. SUMMARY WHAT WAS KNOWN BEFORE * Neovascular age-related macular


degeneration may be considered refractory in case of intra-/subretinal fluid present despite monthly intravitreal anti-VEGF treatment. WHAT THIS STUDY ADDS * Approximately two thirds of


cases showed good short term fluid reduction (more than 50%). * However, around one third of cases showed little change of fluid in between injections. This was more likely in case of larger


baseline fluid amounts, larger baseline PED, presence of polypoidal choroidal vasculopathy, or vitreomacular adherence. * Short-term response was an indicator of visual prognosis, with low


response correlating with poorer visual outcomes after 4 and 5 years of treatment. DATA AVAILABILITY The datasets used and/or analyzed during the current study are available from the


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Download references FUNDING Open access funding provided by University of Lausanne. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Ophthalmology, University of Lausanne, Jules


Gonin Eye Hospital, Foundation Asile des Aveugles, Lausanne, Switzerland Anthony Gigon, Antonio Iskandar, Sophie Kasser, Sacha Naso, Marta Zola & Irmela Mantel Authors * Anthony Gigon


View author publications You can also search for this author inPubMed Google Scholar * Antonio Iskandar View author publications You can also search for this author inPubMed Google Scholar *


Sophie Kasser View author publications You can also search for this author inPubMed Google Scholar * Sacha Naso View author publications You can also search for this author inPubMed Google


Scholar * Marta Zola View author publications You can also search for this author inPubMed Google Scholar * Irmela Mantel View author publications You can also search for this author


inPubMed Google Scholar CONTRIBUTIONS AG: main manuscript writing, data acquisition, statistical analysis. AI: data acquisition, final review of manuscript. SK: data acquisition, final


review of manuscript. SN: data acquisition, final review of manuscript. MZ: data acquisition, final review of manuscript. IM: project conceptualization, statistical analysis, manuscript


writing, final review of the manuscript CORRESPONDING AUTHOR Correspondence to Irmela Mantel. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL


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THIS ARTICLE CITE THIS ARTICLE Gigon, A., Iskandar, A., Kasser, S. _et al._ Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration.


_Eye_ 38, 1342–1348 (2024). https://doi.org/10.1038/s41433-023-02900-6 Download citation * Received: 09 December 2022 * Revised: 22 November 2023 * Accepted: 08 December 2023 * Published: 26


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