Abstract
Background
To evaluate the cost-effectiveness of early- versus late-switch to the intravitreal-dexamethasone implant (DEX-i) in patients with diabetic macular edema (DME) who did not adequately respond to vascular endothelial growth factor inhibitors (anti-VEGF).
Methods
Retrospective analysis of a multicenter Clinical Data Registry. The registry included DME eyes who received 3 intravitreal anti-VEGF injections (early-switch) or > 3 intravitreal anti-VEGF injections (late-switch) before switching to DEX-i injections. The primary outcome was to estimate the incremental cost needed to obtain a best-corrected visual acuity (BCVA) improvement ≥ 0.1 or a central-retinal thickness CRT ≤ 250 μm.
Results
The analysis included 108 eyes, 32 (29.6%) and 76 (70.4%) in the early- and late-switch groups, respectively. Early-switch strategy was associated with a cost saving of €3,057.8; 95% CI: €2,406.4–3,928.4, p < 0.0001). Regarding incremental-cost-effectiveness ratio, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively. At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 micron. As compared to baseline, the mean (95% CI) CRT reduction was − 163.1 (− 212.5 to − 113.7) µm and − 161.6 (− 183.8 to − 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463.
Conclusions
In DME eyes, who did not adequately respond to anti-VEGF, switching to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the treatment to 6-monthly injections of anti-VEGF.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Sociodemographic changes in the population have posed important challenges for health systems. As worldwide elderly population continues to increase and get older, healthcare costs are expected to rise even further. Health systems, therefore, must be increasingly efficient for affording the growing demand of patients affected by chronic diseases [1].
The prevalence of diabetes mellitus (DM), particularly type 2 DM, has been increasing rapidly over the past few decades [2, 3]. Based on data from the International Diabetes Federation, the global prevalence of diabetes has been estimated to be 12.2% (783.2 million people) by 2045 [4], which represents a health expenditure of approximately 845 billion dollars [5].
Diabetic retinopathy (DR) is the leading legal blinding eye disease for working-aged people (accounting for about 2.6% of all vision losses), and diabetic macular edema (DME) secondary to DR is the direct cause of visual impairment [6,7,8].
Vascular endothelial growth factor (VEGF) inhibitors (anti-VEGF) are commonly used as a first-line therapy for DME [9, 10]. However, as many as 30–50% of patients do not respond to anti‐VEGF treatment adequately [11, 12]. Moreover, eyes with a poor response to ranibizumab (those gaining < 5 letters after 3-monthly intravitreal ranibizumab injections) usually do not improve further with continuing in ranibizumab treatment [13] and extending the dose to 24 weeks was not associated with better functional or anatomic outcomes [14].
From a clinical point of view, the relevance of these findings critically depends on whether patients who did not adequately respond to anti-VEGF therapies could benefit from other therapies, especially considering that long-standing DME can permanently damage the retina, which might limit the functional recovery [15].
Intravitreal dexamethasone implant (DEX-i) has proven to have a beneficial impact on both anatomic and functional clinical outcomes since it is capable of acting both on inflammatory and on vasogenic mediators [16,17,18]. Additionally, patients who did not adequately respond to anti‐VEGF treatment should be switched to DEX-i as soon as possible, and preferably after 3 doses of anti-VEGF [19, 20].
Because DME treatment entails a high cost, the suitability of new treatments must be established on the basis of the patient’s benefit.
Despite the clinical, social, and economic relevance of this therapy area, data evaluating the cost effectiveness of DEX-i in DME are limited [21,22,23,24].
In a previous paper, we assessed the clinical and economic consequences of an extension of initial anti-VEGF treatment from 3 to 6 monthly injections in patients with persistent central-involved DME and visual impairment based on the findings of the post hoc analyses of the DRCR.net Protocol T clinical trial. The results of the study showed that for the total number of patients treated, an average of €7927.02 per additional responder patient would be necessary [25].
This study aimed to evaluate the cost-effectiveness of early- versus late-switch to the DEX-i in DME patients who did not adequately respond to anti-VEGF therapies. This study is based on the findings of our previous paper comparing the clinical outcomes of early versus late switch in eyes who did not adequately respond to anti-VEGF therapies and underwent a DEX-I [20].
Methods
Retrospective analysis of a multicenter Clinical Data Registry
A cost-consequence model was developed in Microsoft Excel following recommendations for economic evaluation of health technologies [26]. The model compared the economic implications of switching non-responder patients to 3-monthly intravitreal injections of anti-VEGF to DEX-i (early-switch) to those of extending the anti-VEGF initial treatment from 3 to 6-monthly injections (late-switch).
This analysis was carried out from a hospital pharmacy perspective in which only pharmaceutical treatment costs were considered. Other direct medical costs such as costs of administration were not included as they were beyond the scope of this analysis. The anti-VEGF treatment options included in the model were aflibercept, ranibizumab, and bevacizumab. To estimate the pharmaceutical costs, official ex-factory unit prices were obtained from the General Council of Provincial Pharmacy Chambers database [27]: aflibercept 40 mg/ml (€578.76 per vial), ranibizumab 10 mg/ml (€619.75 per vial) and bevacizumab 25 mg/ml (€262.0 per vial; 4 ml presentation). All the costs included in the analysis reflected the value in euros for the year 2021.
This study analyzed the cost and consequences of the continuation until month 12, of monthly treatment of DME patients with anti-VEGF from month 3 to month 6 versus switching to DEX-i at month 3 in non-responder patients according to the results published in our previous study [20].
Definitions
“Not-adequately” respond to anti-VEGF was defined if after 3 anti-VEGF injections (either ranibizumab, bevacizumab, or aflibercept), there was (1) no improvement in best corrected visual acuity (BCVA) and/or (2) a central retinal thickness (CRT) reduction < 20% and/or (3) recurrence of DME despite monthly anti-VEGF injections and/or (4) similar BCVA but worsening of DME; and/or (5) decreased in BCVA and a CRT thickening [25].
Early-switch: Eyes who did not respond adequately to three-monthly injections of anti-VEGF and were switched to DEX-i.
Late-switch: Eyes who did not respond adequately to three monthly injections of anti-VEGF and received an extending initial treatment of three-monthly anti-VEGF injections up to 6 months.
Calculations
Cost-effectiveness ratio (CER) was calculated as per cost/outcome formula. CER was once calculated by considering the numerical difference of outcomes.
Incremental cost-effectiveness ratio (ICER) was calculated by the numerical difference of outcomes between the early-switch and late-switch groups as the following formula: ICER = (cost in early-switch–cost in late-switch group)/(effectiveness in early-switch group–effectiveness in late switch group).
Outcomes
The primary outcome was to estimate the incremental cost needed to obtain an additional response at month 12 (improvement in BCVA ≥ 0.1 or reduction in CRT ≤ 250 μm) in patients who maintained anti-VEGF therapy versus those who switched to DEX-i.
The secondary outcomes included the cost of achieving different BCVA, changes in BCVA, changes in CRT and subfoveal choroidal thickness (SCT), and the probability of achieving different BCVA.
Statistical analysis
A standard statistical analysis was performed using the MedCalc® Statistical Software version 20.110 (MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org; 2022).
Descriptive statistics number (percentage), mean [standard deviation (SD)], mean [95% confidence interval (95% CI)], or median [Interquartile range (IqR)] were used, as appropriate.
Distribution of quantitative variables was assessed using the D’Agostino-Pearson test.
The Mann–Whitney U test was used in the evaluation of the baseline quantitative variables and the total costs between early-switch and late-switch groups. A repeated measures ANOVA or a Friedman’s two-way analysis test as appropriate were used to assess changes in BCVA and CRT within the groups throughout the study.
The Cochran-Mantel–Haenszel test was used to assess the probability of achieving a BCVA improvement ≥ 0.1 (at any time-point measured and at month 12) or ≥ 0.2 (at any time-point measured and at month 12) with study group as grouping variable and type of DME as factor variable.
Results
Baseline demographic and clinical characteristics
One hundred and eight eyes were included in the analysis, 32 (29.6%) in the early-switch group and 76 (70.4%) in the late-switch group.
In the overall study, sample mean age was 67.6 ± 8.9 years and 30 (27.8%) were women. Twenty-seven (25.0%) eyes were diagnosed with diffuse retinal thickness, 65 (60.2%) with cystoid macular edema, and 16 (14.8%) with serous retinal detachment.
Table 1 shows an overview of the main demographic and clinical characteristics of the study sample. There were no significant differences in any of the baseline variables between the early-switch and late-switch groups.
Cost analysis
The median (Interquartile range) cost was significantly lower in the early-switch (€2724.3; IqR: €1774.0 to €3712.3) than in the late-switch group (€5864.0; IqR: €4384.5 to €7763.6) (Hodges-Lehmann median difference: − 3057.8; 95% CI: 2406.4 to €3928.4, p < 0.0001).
An overview of the study costs is shown in Table 2.
The CER of BCVA improvement ≥ 0.1 at month 12 was € 3,789.0 in the early-switch group and € 12,041.1 in the late-switch one. Early-switch group showed a lower CER in all the outcome measured (Table 2).
Regarding ICER, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively (Table 2).
Changes in BCVA
At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. The probability of achieving a BCVA improvement ≥ 0.2 at any time-point and at month 12 was significantly greater in the early-switch group than in the late-switch one (p = 0.0060 and 0.0224, respectively).
The probability of achieving a specific improvement in BCVA is shown in Table 3.
BCVA was significantly greater in the early-switch group than in the late-switch one at month 8 (mean difference: 0.11; 95% CI: 0.0 to 0.21, p = 0.0311) and month 12 (mean difference: 0.13; 95% CI: 0.04 to 0.23, p = 0.0078). As compared to baseline, BCVA significantly improved in the early-switch group (p = 0.0094, repeated ANOVA test) but not in the late-switch group (p = 0.1617).
The Cochran–Mantel–Haenszel odds ratio of achieving a BCVA gain ≥ 0.1 at any time-point measured was 2.88 (95% CI: 1.12 to 6.82; p = 0.0254) (Table 4).
Changes in CRT and SCT
At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 μm, without significant differences between the early-switch (14/32 eyes, 43.8%) and late-switch groups (38/76, 50.0%), p = 0.6691 (Table 3).
In the early-switch group, DEX-I significantly reduced CRT from 431.3 ± 115.5 µm at baseline to 281.7 ± 69.2 µm, 373.9 ± 126.5 µm, 358.2 ± 108.2 µm, and 269.3 ± 66.2 µm at months 2, 4, 8, and 12, respectively (p < 0.001, repeated measures ANOVA and the Greenhouse–Geisser correction).
Similarly, in the late switch group, mean CRT was significantly reduced from 430.1 ± 130.1 µm at baseline to 276.6 ± 66.6 µm, 380.2 ± 134.8 µm, 361.6 ± 113.4 µm, and 268.6 ± 66.1 µm at months 2, 4, 8, and 12, respectively (p < 0.001, repeated measures ANOVA and the Greenhouse–Geisser correction).
Mean changes in CRT and SCT were similar in early-switch and late switch groups (Fig. 1 A and B, respectively). As compared to baseline, the mean (95% CI) CRT reduction was − 163.1 (− 212.5 to − 113.7) µm and − 161.6 (− 183.8 to − 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463.
Discussion
Public health services have to cope with unlimited demand with limited resources. Further, the imbalance between demand and supply is assumed to be deteriorating as the population ages, new technologies appear, and expectations rise [28]. For everything mentioned so far, it is extremely important to identify cost effective treatments.
DME represent an increasing economic burden to health systems not only due to direct costs but also indirect ones, such as reduced income or an increased need for social support as vision worsens [29]. In addition, it has been estimated that the total cost per patient with DME represents 30% more than that of DM patients without DME [30].
In recent years, the introduction of new therapies for DME has led to a paradigm shift in its clinical management. Furthermore, the choice of treatment options for DME depend critically on individual patient clinical characteristics [9].
Using real-world data, we evaluated the direct medical cost of two different treatment strategies in patients with DME, namely, early-switch (eyes who did not adequately respond to 3-monthly injections of anti-VEGF were switched to DEX-i) versus late-switch (eyes who did not respond properly to 3-monthly injections of anti-VEGF and received an extending initial treatment of 3-monthly anti-VEGF injections up to 6 months, before switching to DEX-i).
According to the results of the current study, early-switch strategy was associated with a total cost saving of € 3057.8. Additionally, late-switch was associated with an ICER of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively.
As far as we know, this is the first study evaluating the cost of extending the anti-VEGF treatment dose before switching to DEX-i.
In a previous paper published by our group, we evaluated the cost of extending the anti-VEGF treatment from 3 to 6 monthly injections [25]. This study revealed the incremental costs of extending the anti-VEGF dose in central-involved DME patients who initially did not respond adequately to treatment.
Although extending the anti-VEGF dose from 3 to 6 monthly injections has been associated with better outcomes [14, 31], this option involves treating all patients, regardless the final outcome.
In fact, extending the anti-VEGF initial treatment from 3 to 6 intravitreal injections has entailed a cost increased of €5882.77, €10,091.03, and €10,198.59 per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively [25].
The economic impact of the introduction of DEX-i for the treatment of DME on the Spanish National Health System was estimated using a 3-year budget impact model [32]. This study concluded that the introduction of DEX-i in the Spanish market resulted in significant cost savings, due mainly to fewer injections with DEX-i [32].
In the current study, switching to DEX-i was associated better functional outcomes in the early-switch group and with better anatomic outcomes in both early-switch and late switch groups.
Real-world data have suggested that in DME eyes who did not adequately respond to anti-VEGF, switching to DEX-i is a feasible and safe strategy [19, 20, 33,34,35,36,37].
The results of these studies point in the same general direction, indicating that in patients who did not adequately respond to anti-VEGF therapy, switching to DEX-i provides better functional and anatomical outcomes [19, 20, 33,34,35,36].
The current study found a significant improvement in BCVA in the early-switch group, but not in the late-switch one. In DME patients, there seems to be an association between BCVA improvement and external limiting membrane (ELM) integrity [38, 39]. This may suggest a significant relationship between ELM integrity and photoreceptor cell bodies status, which may be a sign of advanced photoreceptor damage [38, 39]. DEX-i significantly improved ELM integrity, which was correlated with a significant with the upturn in BCVA [40]. Since the baseline integrity of ELM was associated with better functional outcomes, it makes sense to assume that an early recovery of these structures would be associated with better functional outcomes [41]. These findings may explain the differences in functional outcomes between the early switch and late switch groups observed in our study. However, further studies are needed to confirm this assumption.
Regarding the anatomic outcomes, our study found a significant reduction in CRT, without differences between groups. These findings are in agreement with the current evidence [19, 20, 33,34,35,36].
Our study has some limitation that need to be taken into account when interpreting the results. Although this study used data from a cohort of patients from three centers in its model, the number of eyes and the geographical distribution of the sample may limit the generalization of the results obtained. Nevertheless, as an important strength of our study, it collects real-world data, which are more representative of the unselected population that we usually attend in our daily clinical practice [42]. Additionally, our study did not evaluate direct non-medical-related costs (i.e. home healthcare and social services), patient transportation, or other incidentals, to establish economic parameters.
Conclusions
In DME patients who do not adequately respond to anti-VEGF switch to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the initial treatment to 6-monthly injections of anti-VEGF. Additionally, DEX-i significantly improved the anatomic outcomes in difficult cases that have failed to respond to previous anti-VEGF therapies. However, the functional outcomes were significantly improved only in the early-switch group, which speak in favor of switching to DEX-i as soon as possible.
Although anti-VEGF are currently considered as the first line therapy in DME patients, many patients do not adequately respond to them. Therefore, further studies will be necessary to determine the most cost-effective treatment according to the patient’s profile.
Data availability
Data not here published are obtainable on reasonable request from the corresponding author.
References
Kaplan MA, Inguanzo MM (2017) The social, economic, and public health consequences of global population aging: implications for social work practice and public policy. Journal of Social Work in the Global Community, vol. 2, no 1, p. 1. Available in: https://scholarworks.waldenu.edu/jswgc/vol2/iss1/1/ Last accessed June 1, 2022.
Zheng Y, Ley SH, Hu FB (2018) Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 14(2):88–98. https://doi.org/10.1038/nrendo.2017.151
NCD Risk Factor Collaboration (2016) Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet 387(1513–1530):2022. https://doi.org/10.1016/S0140-6736(16)00618-8LastaccessedJune1
Sun H, Saeedi P, Karuranga S et al (2022) IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183:109119. https://doi.org/10.1016/j.diabres.2021.109119
Williams R, Karuranga S, Malanda B, et al., (2020) Global and regional estimates and projections of diabetes-related health expenditure: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 162:108072. https://doi.org/10.1016/j.diabres.2020.108072.
Varma R, Bressler NM, Doan QV et al (2014) Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol 132(11):1334–1340. https://doi.org/10.1001/jamaophthalmol.2014.2854
Leasher JL, Bourne RR, Flaxman SR et al (2016) Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis From 1990 to 2010. Diabetes Care 39(9):1643–1649. https://doi.org/10.2337/dc15-2171.Erratum.In:DiabetesCare39(11):2096
Miller K, Fortun JA (2018) Diabetic macular edema: current understanding, pharmacologic treatment options, and developing therapies. Asia Pac J Ophthalmol (Phila) 7(1):28–35. https://doi.org/10.22608/APO.2017529.
Schmidt-Erfurth U, Garcia-Arumi J, Bandello F et al (2017) Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica 237(4):185–222. https://doi.org/10.1159/000458539
Virgili G, Parravano M, Evans JR, Gordon I (2018) Lucenteforte E (2018) Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 10(10):CD007419. https://doi.org/10.1002/14651858.CD007419.pub6
Duh EJ, Sun JK, Stitt AW (2017) Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight 2(14):e93751. https://doi.org/10.1172/jci.insight.93751
Shah AR, Yonekawa Y, Todorich B et al (2017) Prediction of anti-VEGF response in diabetic macular edema after 1 injection. J Vitreoretin Dis 1(3):169–174. https://doi.org/10.1177/2474126416682569
Gonzalez VH, Campbell J, Holekamp NM et al (2016) Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol 172:72–79. https://doi.org/10.1016/j.ajo.2016.09.012
Bressler NM, Beaulieu WT, Glassman AR et al (2018) Persistent macular thickening following intravitreous aflibercept, bevacizumab, or ranibizumab for central-involved diabetic macular edema with vision impairment: a secondary analysis of a randomized clinical trial. JAMA Ophthalmol 136(3):257–269. https://doi.org/10.1001/jamaophthalmol.2017.6565.Erratum.In:JAMAOphthalmol1;136(5):601
Murakami T, Yoshimura N (2013) Structural changes in individual retinal layers in diabetic macular edema. J Diabetes Res 2013:920713. https://doi.org/10.1155/2013/920713
Lazic R, Lukic M, Boras I et al (2014) Treatment of anti-vascular endothelial growth factor-resistant diabetic macular edema with dexamethasone intravitreal implant. Retina 34(4):719–724. https://doi.org/10.1097/IAE.0b013e3182a48958.
Karti O, Saatci AO (2021) Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema. World J Diabetes 12(8):1220–1232. https://doi.org/10.4239/wjd.v12.i8.1220
Ehlers JP, Yeh S, Maguire MG et al (2022) Intravitreal pharmacotherapies for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology 129(1):88–99. https://doi.org/10.1016/j.ophtha.2021.07.009
Busch C, Zur D, Fraser-Bell S et al (2018) Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema. Acta Diabetol 55(8):789–796. https://doi.org/10.1007/s00592-018-1151-x
Ruiz-Medrano J, Rodríguez-Leor R, Almazán E et al (2021) Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: early versus late switch. Eur J Ophthalmol 31(3):1135–1145. https://doi.org/10.1177/1120672120929960
Lozano López V, Serrano García M, Mantolán Sarmiento C et al (2015) Resultados coste-efectividad del implante de dexametasona en edema macular [A cost-effectiveness study of dexamethasone implants in macular edema]. Arch Soc Esp Oftalmol 90(1):14–21. https://doi.org/10.1016/j.oftal.2013.10.007 (Spanish)
Foglia E, Ferrario L, Bandello F et al (2018) Diabetic macular edema, innovative technologies and economic impact: new opportunities for the Lombardy Region healthcare system? Acta Ophthalmol 96(4):e468–e474. https://doi.org/10.1111/aos.13620
Cho H, Choi KS, Lee JY et al (2019) (2019) Healthcare resource use and costs of diabetic macular oedema for patients with antivascular endothelial growth factor versus a dexamethasone intravitreal implant in Korea: a population-based study. BMJ Open 9(9):e030930. https://doi.org/10.1136/bmjopen-2019-030930
Pesonen M, Kankaanpää E, Vottonen P (2021) Cost-effectiveness of dexamethasone and triamcinolone for the treatment of diabetic macular oedema in Finland: a Markov-model. Acta Ophthalmol 99(7):e1146–e1153. https://doi.org/10.1111/aos.14745
Ruiz-Moreno JM, de Andrés-Nogales F, Oyagüez I (2020) Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients. BMC Ophthalmol 20(1):371. https://doi.org/10.1186/s12886-020-01637-0
López-Bastida J, Oliva J, Antoñanzas F et al (2010) Spanish recommendations on economic evaluation of health technologies. Eur J Health Econ 11(5):513–520. https://doi.org/10.1007/s10198-010-0244-4
Consejo General de Colegios Oficiales de Farmacéuticos. Base de datos del Conocimiento Sanitario - Bot Plus 2.0 [Health Knowledge database – Bot Plus 2.0]. Consejo General de Colegios Oficiales de Farmacéuticos, 2019 Available in: https://botplusweb.portalfarma.com/. Last Accessed June 1, 2022.
Frankel S, Ebrahim S, Davey Smith G (2000) The limits to demand for health care. BMJ 321(7252):40–45. https://doi.org/10.1136/bmj.321.7252.40
Lafuma A, Brézin A, Lopatriello S et al (2006) Evaluation of non-medical costs associated with visual impairment in four European countries: France, Italy. Germany and the UK Pharmacoeconomics 24(2):193–205. https://doi.org/10.2165/00019053-200624020-00007
Shea AM, Curtis LH, Hammill BG et al (2008) Resource use and costs associated with diabetic macular edema in elderly persons. Arch Ophthalmol 126(12):1748–1754. https://doi.org/10.1001/archopht.126.12.1748
Bressler SB, Ayala AR, Bressler NM et al (2016) Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol 134(3):278–285. https://doi.org/10.1001/jamaophthalmol.2015.5346
Cervera E, De Andrés-Nogales F, Armadá F, Arias L, Oyagüez I, Martínez C (2018) Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema. Farm Hosp 42(6):244–250. https://doi.org/10.7399/fh.11016 (English)
Cicinelli MV, Cavalleri M, Querques L, Rabiolo A, Bandello F, Querques G (2017) Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema. Br J Ophthalmol 101(12):1689–1693. https://doi.org/10.1136/bjophthalmol-2017-310242
Demir G, Ozkaya A, Yuksel E et al (2020) Early and late switch from ranibizumab to an intravitreal dexamethasone implant in patients with diabetic macular edema in the event of a poor anatomical response. Clin Drug Investig 40(2):119–128. https://doi.org/10.1007/s40261-019-00865-7
Hernández Martínez A, Pereira Delgado E, Silva G et al (2020) Early versus late switch: how long should we extend the anti-vascular endothelial growth factor therapy in unresponsive diabetic macular edema patients? Eur J Ophthalmol 30(5):1091–1098. https://doi.org/10.1177/1120672119848257
Hsia NY, Lin CJ, Chen HS et al (2021) Short-term outcomes of refractory diabetic macular edema switch from ranibizumab to dexamethasone implant and the influential factors: a retrospective real world experience. Front Med (Lausanne) 8:649979. https://doi.org/10.3389/fmed.2021.649979
Scorcia V, Giannaccare G, Gatti V et al (2021) Intravitreal dexamethasone implant in patients who did not complete anti-VEGF loading dose during the COVID-19 pandemic: a retrospective observational study. Ophthalmol Ther 10(4):1015–1024. https://doi.org/10.1007/s40123-021-00395-6
Muftuoglu IK, Mendoza N, Gaber R, Alam M, You Q, Freeman WR (2017) Integrity of outer retinal layers after resolution of central involved diabetic macular edema. Retina 37(11):2015–2024. https://doi.org/10.1097/IAE.0000000000001459
Rangaraju L, Jiang X, McAnany JJ et al (2018) Association between visual acuity and retinal layer metrics in diabetics with and without Macular Edema. J Ophthalmol 2018:1089043. https://doi.org/10.1155/2018/1089043
Iacono P, Parodi MB, Scaramuzzi M, Bandello F (2017) Morphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Br J Ophthalmol 101(6):791–795. https://doi.org/10.1136/bjophthalmol-2016-308726
Campochiaro PA, Aiello LP, Rosenfeld PJ (2016) Anti-vascular endothelial growth factor agents in the treatment of retinal disease: from bench to bedside. Ophthalmology 123(10S):S78–S88. https://doi.org/10.1016/j.ophtha.2016.04.056
Cohen AT, Goto S, Schreiber K, Torp-Pedersen C (2015) Why do we need observational studies of everyday patients in the real-life setting?: Table 1. European Heart Journal Supplements D2–D8. doi.org/https://doi.org/10.1093/eurheartj/suv035. Available in: https://academic.oup.com/eurheartjsupp/article/17/suppl_D/D2/2949926 Last accessed June 3, 2022.
Acknowledgements
Medical writing and editorial assistant services have been provided by Antonio Martínez (MD) of Ciencia y Deporte S. L.
Funding
The medical writer and editorial assistance for this manuscript was supported by AbbVie with no input into the preparation, review, approval, and writing of the manuscript. The authors maintained complete control over the manuscript content, and it reflects their opinions.
Author information
Authors and Affiliations
Contributions
All authors met the ICMJE authorship criteria. All authors made substantial contributions to conception, design, analysis, and interpretation of data; contributed to writing the article; provided critical revision of the manuscript; and approved the final version.
Corresponding authors
Ethics declarations
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethic Committee of the Puerta de Hierro-Majadahonda University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Due to the characteristics of the study, the Ethic Committee of the Puerta de Hierro-Majadahonda University Hospital waived the need for written informed consent.
Conflict of interest
Dr Ruiz-Moreno has received a grant from Allergan during the conduct of the study. Neither honoraria nor payments were made for authorship of this article. Dr Ruiz-Medrano certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Ruiz-Moreno, J.M., Ruiz-Medrano, J. Early-switch versus late-switch in patients with diabetic macular edema: a cost-effectiveness study. Graefes Arch Clin Exp Ophthalmol 261, 941–949 (2023). https://doi.org/10.1007/s00417-022-05892-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-022-05892-3