Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study

Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study Joonas Wirkkala, Anna-Maria Kubin, Pasi Ohtonen, Joona Yliselä, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1517031/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background: The treatment for diabetic macular edema (DME) has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents. The aim of the current study is to evaluate the real-world visual outcomes of diabetic macular edema (DME) treatment in patients with type 1 diabetes (T1D) in long-term follow-up. Methods: A real-world, descriptive, population-based cohort and follow-up of all patients with T1D and DME in 2006-2020 in 34 communities of the Northern Ostrobothnia Hospital District. The main outcome measures included age, gender, duration of T1D at the onset of DME, stage of retinopathy, treatment of DME (observation, laser, intravitreal treatments, combination), and visual outcomes. Results: A total of 304 eyes of 206 T1D patients with DME were included. 75% (n=155) had non-proliferative diabetic retinopathy during the onset of DME. 15% of the cases were observed, 33% had macular laser, 41% intravitreal anti-VEGF and 12% combination of laser and intravitreal injections. Patients in anti-VEGF and in combination groups gained 4.9 and 5.5 ETDRS letters after the initial DME (p<0.001 and p<0.001), and the long-term visual improvements were 4.1 and 5.1 ETDRS letters (p<0.001 and p<0.001), respectively. The average of 6.1土4.8 anti-VEGF injections were needed to dry DME. Visual impairment due to DME decreased from 2.4% to 1.0% during15 years. Conclusion: Early intensive treatment by anti-VEGF alone or in combination with macular laser seems to be beneficial in terms of better visual outcomes and treatment stability in T1D patients with DME, whereas a slight decrease in vision was noted in observation or laser groups. Moreover, satisfying long-term visual outcomes were commonly achieved with anti-VEGF treatment in a real-world setting. Type 1 diabetes diabetic macular edema anti-VEGF agents diabetic retinopathy Background A recent study has estimated the 0.5% national prevalence of type 1 diabetes (T1D) among adults in the US, which accounted for 5.6% of all diagnosed diabetes ( 1 ). A recent meta-analysis estimated the global prevalence of any diabetic retinopathy (DR) in T1D to be 77% and that of proliferative diabetic retinopathy (PDR) to be 32% ( 2 ). 4–12% prevalence of diabetic macular edema (DME) in patients with T1D has been reported ( 3 ). The number of visual impairment due to DR has decreased during the past decades despite the increasing number of diabetes ( 4 , 5 ). More effective screening for DR, the development of the non-invasive optical coherence tomography (OCT) in the diagnosis of DME, introduction of intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) agents, as well as improvements in the management of diabetes, have been the key factors in the reduction of visual impairment ( 6 ) ,(7) . Lately, DME rather than PDR has been the increasingly common cause of visual impairment ( 5 ). Anti-VEGF agents are currently widely used in treatment of DME and considered the first-line treatment in clinically significant DME ( 8 ). Despite the great number of previous studies evaluating anti-VEGF treatment in DME during the last decade, there are, to our knowledge, no studies reporting the long-term real-world DME treatment outcomes solely in patients with T1D. It has been established that the clinical features and risk factors for DME might vary in patients with T1D from patients with T2D ( 9 ). The aim of the current descriptive population-based cohort and follow-up of all patients with T1D and DME is to evaluate DME outcomes in a real-world setting and to explore the effect of the choice of treatment (observation, laser, intravitreal anti-VEGF or combination of laser and anti-VEGF) on long-term visual outcomes. Also, the number of intravitreal injections needed to treat DME, and the rate of DME-related visual impairment are studied. Methods This work was carried out at the Oulu University Hospital. The study followed the tenets of the Declaration of Helsinki and it was conducted with the approval of the Oulu University Hospital Research Committee (175/2016). Involvement of patients or the public in the design, or conduct, or reporting, or dissemination plans of the current research was not appropriate. A written informed consent was obtained from the participants. This retrospective population-based cohort study was performed on all adult patients with T1D, who presented at the Oulu University Hospital with DME between June 1, 2006 and Dec 31, 2020. All cases of DME observed or treated by laser, intravitreal anti-VEGF injections or vitrectomy in the area were included in the study. The hospital’s electronic patient database was used to search for the patients with DME in T1D by using the ICD-10 (International Classification of Diseases) diagnosis codes for diabetic maculopathy (H36.1) and type 1 diabetes (E10.3). Optical coherence tomography (OCT) was used to demonstrate the intra- or subretinal fluid in the macula, and central retinal thickness ≥ 300 µm was considered as clinically significant macular edema. Demographic data was collected and included parameters for age, gender, age at the diabetes onset, duration of the diabetes at the onset of both DR and DME, stage of DR during the onset of DME, treatment of DR and DME (observation, laser, intravitreal treatments, vitrectomy) and the time of the follow-up. The best corrected visual acuity (BCVA) was evaluated routinely by the use of the Snellen chart during the DME treatment and follow-up. The BCVA results were converted to ETDRS (Early Treatment of Diabetic Retinopathy Study)-letters in order to calculate changes in vision. The severity of DR was based on the 5-scale classification system by Finnish Current Care Guidelines of Diabetic Retinopathy ( 10 ). For the use of laser or intravitreal treatment, the current protocols, and guidelines of DME treatment were adhered to ( 8 , 10 ). As a rule, the patients with extrafoveal macular edema located ≥ 500 µm from the central fovea were either observed or subjected to macular laser depending on the location and amount of intraretinal or subretinal fluid. Those with central macular edema within 500 µm from the fovea were primarily subjected to intravitreal anti-VEGF treatment. The patients were subjected to combination treatment with anti-VEGF and macular laser in cases of subsequent central and extrafoveal edema. The recurrence of DME was considered if there were no intraretinal or subretinal fluid in the macular OCT between the separate episodes of DME. In Finland, bevacizumab is commonly used as the first-line intravitreal drug for DME. SPSS (IBM Statistical Analysis) version 27.0 was used for the statistical analysis of the data. Summary statistics are presented as mean with standard deviation (SD) unless otherwise stated. Linear mixed model (LLM) was used to compare the change in vision from baseline to the end of follow-up, where patient and eye were set as random effect and sex, age and time from the diagnosis of T1D as adjusting factors. Mean change with a 95% confidence interval is presented as the result of LLM. Two-tailed p-values < 0.05 are considered as statistically significant. Results A total of 206 patients (304 eyes) with T1D and DME were included in the population-based study cohort, out of which 121 (59%) were males. The average age at the time of diagnosis of T1D was 23.4土16.5 years of age (range 1–79 years). The duration of diabetes at the diagnosis of any DR was 16.4土9.7 years (range 0–53 years) and that of DME 24.0土11.9 years (range 0–53 years). The average age of the patients at the onset of DME was 47.4土14.4 years (range 18–85 years). 155 patients (75%) had non-proliferative DR (NPDR) during the time of diagnosis of DME and only 51 patients (25%) had developed proliferative diabetic retinopathy (PDR). During the study period, there were 304 initial episodes of DME in 206 patients with T1D. Including the recurrences, a total of 456 episodes of DME in 304 eyes of the patients were noted. The average follow-up time of a single patient was 65土45 months (range 4-236 months). There were 18 deaths (9%) among the patients during the 15-year study period. The demographics are presented in Table 1 . Table 1. Characteristics of the participants. In a total of 45 DME episodes (15%) the patients were observed with no treatment for DME. The patients had macular laser treatment in 100 (33%), intravitreal anti-VEGF in 124 (41%) and combination of laser and intravitreal injections in 35 (12%) cases of DME. During the follow-up period between the years 2006–2020, the use of intravitreal agents has significantly increased after established treatment practices have become more common after the first years of availability of these drugs. An average baseline BCVA at the time of diagnosis of DME was 76.9土12.5 ETDRS letters (range 15.1–95.2 ETDRS letters). At the onset of DME, five T1D patients (2.4%) were visually impaired according to classification of visual impairment by the World Health Organization (WHO). However, treatment of DME improved the BCVA in several cases, and at the end of follow-up, only two of these patients (1.0%) met the criteria of visual impairment. After the initial DME, there was no significant change in BCVA in the observation group (gain of 0.1 ETDRS letters, p > 0.90). A small, 0.4 ETDRS letter decrease was noted in the laser group (p = 0.61). Improvements of BCVA of 4.9 (p < 0.001) and 5.5 (p < 0.001) ETDRS letters were documented in the anti-VEGF and combination (anti-VEGF and laser) groups after the preliminary episode of DME, respectively. In addition, patients treated with either anti-VEGF agents alone or in combination with laser, received statistically significant long-term improvements of 4.1 (p < 0.001) and 5.1 (p 0.90) and a 1.1 (p = 0.14) ETDRS letter decline in the laser group of patients. The visual outcomes of the alternative treatments of DME are presented in Table 2 . Table 2. Ophthalmological outcomes. A great majority, over 99%, of the DME patients treated by intravitreal agents received bevacizumab as a first-line drug. In only a single case (0.6%), aflibercept was used as a primary choice for anti-VEGF treatment. In 15% (n = 24) of the cases, the switch from bevacizumab to aflibercept was documented at some phase of the follow-up. An average of 6.1土4.8 injections of either anti-VEGF drug (6.0 in anti-VEGF group and 6.5 in the combination group, range 1–33) were needed to treat DME, and most injections were emphasized to a first treatment year. None of these patients received intravitreal corticosteroid or underwent vitrectomy. In just over a third (37%) of the cases, there was only a single episode of DME during the follow-up period (Table 2 ). Depending on the choice of the primary treatment there seems to be differences between the groups in the stability of the treatment outcomes in the terms of the renewal of DME: the recurrence occurred in 91% of the cases in the observation group, 59% of the cases in the laser group, 65% of the cases in the anti-VEGF group and 37% of the cases in the combination group of laser and anti-VEGF during the average follow-up period of 65 months. Discussion The duration of diabetes, poor glycemic control, high blood pressure and proteinuria are known risk factors when observing the development of diabetes related complications ( 11 ). Globally, DR has been one of the leading causes of blindness among the working age population and the most common complication of T1D ( 12 ). However, the number of visual impairment due to DR has decreased during the past decades ( 7 , 13 ). More effective screening for DR and improvement in the management of both diabetes and DR have been key factors in the reduction of visual impairment ( 7 ). Accordingly, DME related visual impairment was rare and reduced in the present study during the 15-year follow-up in a population-based cohort of T1D patients with DME. We might assume that the improvements in both diagnostic accuracy and treatment possibilities of DME during the past 15 years have played an important role in this phenomenon. Warwick et al. has reported that DME is associated with the duration of diabetes ( 3 ). In agreement with this, our results showed that in T1D patients DME developed almost 10 years later than the first signs of DR. One may speculate that the prevalence of DME increases along the severity of DR. However, only less than one fourth of the study patients with DME had PDR. Previous study has revealed a high 94% prevalence of any DR and 35% prevalence of PDR in patients with T1D since childhood and duration of T1D for over twenty years ( 14 ). The T1D patients with DME in the present study differ from this cohort of patients with T1D since childhood, according to older age at the onset of diabetes and the lower prevalence of PDR. The treatment for DME has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents ( 7 , 15 ). Laser photocoagulation has been the standard treatment for DME for almost three decades, but currently anti-VEGF agents are considered the first line treatment alternative in center-involving DME ( 8 ). Several large clinical trials have demonstrated that the improvement of BCVA > 15 ETDRS letters has been achieved by anti-VEGF agents in 33–45% of patients with either type 1 or type 2 diabetes ( 8 , 16 ) ,(17) . Superior visual outcomes have been reported by ranibizumab treatment compared to treatment performed by laser, and a higher proportion of patients has gained significant > 10–15 ETDRS letter increase in BCVA when treated with anti-VEGF ( 6 ). Similarly, the BOLT study has revealed that the number of DME patients gaining > 15 ETDRS letters was significantly greater when treated with bevacizumab compared to macular laser ( 18 , 19 ). In agreement with these results, DME patients gaining the most ETDRS letters in the current real-world study were treated by bevacizumab and the best long-term visual outcomes were achieved with combination treatment with both anti-VEGF and macular laser. However, previous studies have suggested that DME patients with relatively good BCVA could be observed when BCVA remains stable ( 20 – 22 ). Our real-world results show, however, a decrease in BCVA in the observation group of patients receiving no treatment in the long term, suggesting that the early treatment of DME might be reasonable to maintain good vision. This is of particular importance when considering the necessity of functional vision for these working-aged, relatively young patients with T1D. Accordingly, the benefits of early intensive treatment by anti-VEGF has recently been shown to result in satisfying long-term visual outcomes ( 23 ). Even in the cases of no BCVA improvement, anti-VEGF treatment may improve contrast sensitivity in DME patients ( 20 ), and thus provide the best long-time safety in maintaining good visual function. Beyond VEGF, the presence of inflammation is known to affect DME pathogenesis and intravitreal corticosteroids may be used to treat DME ( 8 ). In our T1D patient cohort none of the patients received intravitreal corticosteroids. This might be explained by the known side-effects of corticosteroids, such as cataract development or possible increase in intraocular pressure ( 24 ). Most study patients, at the average age of 47 years, might be assumed not to have sight-threatening cataract, and the formation of cataract might thus be attempted to avoid by using primarily anti-VEGF drugs classified with a positive safety profile. There are some limitations in our study. First, the retrospective nature of the study might affect the assembly of different treatment groups and thus comparison of the outcomes. Understandably, baseline visual acuities varied according to the presence or lack of central-involving edema in the participants, although there were no defined BCVA-level for the choice of each treatment. Taking this into consideration, the intra- but no intergroup analysis in the long-term changes in BCVA were completed. Secondly, the underlying risk factors for DME were only partly available, and precise data of the blood glucose levels, cholesterol and kidney function were lacking. Thirdly, the current data did not include any patients treated with intravitreal corticosteroids and the visual outcomes of that treatment cannot be concluded. We consider the inclusion of only T1D patients with DME as part of the current study as a strength in contrast to most studies that are completed with patients with both type 1 and type 2 diabetes. There are significant differences in the pathogenesis as well as risk factors for DME between these patient groups and combining them might be a possible source of bias. Also, the real-world setting and long-term follow-up of the population-based cohort might be considered as strengths of the present study. In conclusion, our results suggest that early intervention of DME by intravitreal anti-VEGF treatment alone or in combination with laser might be beneficial in terms of visual improvement in patients with T1D. Visual acuity slightly decreased or remained stable in those observed or treated with laser, respectively. A low rate of DME recurrences and the beneficial effect on contrast sensitivity ( 20 , 24 ) highlight the importance of timely anti-VEGF in maintaining good visual function in patients with DME. Conclusions During the past 15 years, anti-VEGF agents have become the first-line treatment for center-involving DME after laser photocoagulation being the golden standard treatment for DME for almost three decades. Though the benefits of anti-VEGF agents are well-known, the knowledge of long-term visual prognosis of patients with T1D and DME is still lacking. This study reports, for the first time, long-term, real-world DME treatment outcomes solely in patients with T1D since the clinical features and risk factors for DME in T1D differ from those of T2D. Early intensive treatment by anti-VEGF alone, or in combination with macular laser, seems to improve visual outcomes and treatment stability the most in T1D patients with DME. Declarations Ethics approval and consent to participate: The study followed the tenets of the Declaration of Helsinki and it was conducted with the approval of the Oulu University Hospital Research Committee (175/2016). A written informed consent was obtained from the participants. Consent for publication: Not applicable Availability of data and materials: The datasets generated during and analyzed during the current study are not publicly available due to confidentiality of data-protected patient information but are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: Not applicable Authors' contributions: Each author (JW, AK, PO, JY, TS, NH) has made substantial contributions to the study. NH: Conception of the study, designing the work, data acquisition and analysis, interpretation of the data and writing the manuscript. JW, AK, PO: Design of the work, analysis, and interpretation of the data and substantive revision of the manuscript. JW, JY & TS: Data acquisition, interpretation of the data and substantive revision of the manuscript. All authors have approved the submitted version and agreed both to be personally accountable for their own contributions and to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated, resolved, and the resolution documented in the literature. Acknowledgements: Not applicable References Xu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018 Sep 4;362:k1497. Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556–64. Warwick AN, Brooks AP, Osmond C, Krishnan R, Medscape. Prevalence of referable, sight-threatening retinopathy in type 1 diabetes and its relationship to diabetes duration and systemic risk factors. Eye. 2017 Feb;31(2):333–41. Teo ZL, Tham Y-C, Yan Yu MC, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology [Internet]. 2021 Apr 30; Available from: http://dx.doi.org/10.1016/j.ophtha.2021.04.027 Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss [Internet]. Vol. 2, Eye and Vision. 2015. Available from: http://dx.doi.org/10.1186/s40662-015-0026-2 Mitchell P, Wong TY, Diabetic Macular Edema Treatment Guideline Working Group. Management paradigms for diabetic macular edema. Am J Ophthalmol. 2014 Mar;157(3):505–13.e1–8. Hautala N, Aikkila R, Korpelainen J, Keskitalo A, Kurikka A, Falck A, et al. Marked reductions in visual impairment due to diabetic retinopathy achieved by efficient screening and timely treatment. Acta Ophthalmol. 2014 Sep;92(6):582–7. Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017 Apr 20;237(4):185–222. Hainsworth DP, Bebu I, Aiello LP, Sivitz W, Gubitosi-Klug R, Malone J, et al. Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study. Diabetes Care. 2019 May;42(5):875–82. Summanen P, Kallioniemi V, Komulainen J, Eriksson L, Forsvik H, Hietala K, et al. [Update on Current Care Guideline: Diabetic retinopathy]. Duodecim. 2015;131(9):893–4. Donaghue KC, Marcovecchio ML, Wadwa RP, Chew EY, Wong TY, Calliari LE, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes. 2018 Oct;19 Suppl 27:262–74. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984 Apr;102(4):520–6. Thomas RL, Halim S, Gurudas S, Sivaprasad S, Owens DR. IDF Diabetes Atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018. Diabetes Res Clin Pract. 2019 Nov;157:107840. Hautala N, Hannula V, Palosaari T, Ebeling T, Falck A. Prevalence of diabetic retinopathy in young adults with type 1 diabetes since childhood: the Oulu cohort study of diabetic retinopathy [Internet]. Vol. 92, Acta Ophthalmologica. 2014. p. 749–52. Available from: http://dx.doi.org/10.1111/aos.12426 Ehlers JP, Yeh S, Maguire MG, Smith JR, Mruthyunjaya P, Jain N, et al. Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology. Ophthalmology [Internet]. 2021 Aug 23; Available from: http://dx.doi.org/10.1016/j.ophtha.2021.07.009 Browning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol. 2018 Dec;66(12):1736–50. Urias EA, Urias GA, Monickaraj F, McGuire P, Das A. Novel therapeutic targets in diabetic macular edema: Beyond VEGF. Vision Res. 2017 Oct;139:221–7. Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, et al. A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema (BOLT Study) [Internet]. Vol. 117, Ophthalmology. 2010. p. 1078–86.e2. Available from: http://dx.doi.org/10.1016/j.ophtha.2010.03.045 Rajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD, et al. A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema [Internet]. Vol. 130, Archives of Ophthalmology. 2012. Available from: http://dx.doi.org/10.1001/archophthalmol.2012.393 Beaulieu WT, Glassman AR, Baker CW, Maguire MG, Johnson CA, Melia M, et al. Effect of Initial Aflibercept, Laser, or Observation on Low-Contrast Visual Acuity in Eyes With Diabetic Macular Edema and Good Vision: Ancillary Study Within a Randomized Clinical Trial. Transl Vis Sci Technol. 2021 Mar 1;10(3):3. Baker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, et al. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA. 2019 May 21;321(19):1880–94. Glassman AR, Baker CW, Beaulieu WT, Bressler NM, Punjabi OS, Stockdale CR, et al. Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Apr 1;138(4):341–9. Zirpel JJ, Pfister IB, Gerhardt C, Garweg JG. Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland. Graefes Arch Clin Exp Ophthalmol [Internet]. 2021 May 4; Available from: http://dx.doi.org/10.1007/s00417-021-05187-z Rittiphairoj T, Mir TA, Li T, Virgili G. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2020 Nov 17;11:CD005656. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 12 Apr, 2022 Editor invited by journal 11 Apr, 2022 Submission checks completed at journal 11 Apr, 2022 First submitted to journal 02 Apr, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1517031","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":97637700,"identity":"8e09a12f-7df4-40a8-92c2-fbe73ab5ff16","order_by":0,"name":"Joonas Wirkkala","email":"","orcid":"","institution":"Department of Ophthalmology, Oulu University Hospital, PEDEGO Research Unit and Medical Research Center, University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Joonas","middleName":"","lastName":"Wirkkala","suffix":""},{"id":97637701,"identity":"69d2118f-e8af-4e71-99f7-c176e80dc1fc","order_by":1,"name":"Anna-Maria Kubin","email":"","orcid":"","institution":"Department of Ophthalmology, Oulu University Hospital, PEDEGO Research Unit and Medical Research Center, University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anna-Maria","middleName":"","lastName":"Kubin","suffix":""},{"id":97637702,"identity":"749bf065-cff2-41e4-ad81-383be7d85151","order_by":2,"name":"Pasi Ohtonen","email":"","orcid":"","institution":"Research Service Unit, Oulu University Hospital, Research Unit of Surgery, Anesthesiology and Intensive care, University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pasi","middleName":"","lastName":"Ohtonen","suffix":""},{"id":97637704,"identity":"367b0780-600c-4769-96a1-8da01e10433a","order_by":3,"name":"Joona Yliselä","email":"","orcid":"","institution":"PEDEGO Research Unit and Medical Research Center, University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Joona","middleName":"","lastName":"Yliselä","suffix":""},{"id":97637705,"identity":"2ca6296a-a5cf-40b0-b0ac-e8656c5e0448","order_by":4,"name":"Taru Siik","email":"","orcid":"","institution":"PEDEGO Research Unit and Medical Research Center, University of Oulu","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Taru","middleName":"","lastName":"Siik","suffix":""},{"id":97637707,"identity":"4f3f1cd5-f3e8-41b0-a1df-4e65283d2285","order_by":5,"name":"Nina Hautala","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACZiBmbACzGhg+MDDIALkPDhClhQdIMs4A0QzMBvi1MCBpYeaBasGr2pyd9+AHxh12ifvZDzZ+tqk4zGNwgJkRry2WzXzJEoxnkhN7eBKbpXPOgLUw4NViAFQjwdjGnNjDkNggndsG0sJ/gJAW4x+MbfWJPfwPm39bthFnixnQlsOJPRKJbdKMxGqxSGw7btxz42GbZc+ZdB7Jw4S0nD9jfONjW7Vse3/y4Rs/Kqzl+I43M3/ApwUMElB4zATVj4JRMApGwSggBADf3kkBLjgPkwAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Ophthalmology, Oulu University Hospital, PEDEGO Research Unit and Medical Research Center, University of Oulu","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nina","middleName":"","lastName":"Hautala","suffix":""}],"badges":[],"createdAt":"2022-04-02 15:14:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1517031/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1517031/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20298627,"identity":"c796ed30-eb17-4901-b17e-ddbc415ae820","added_by":"auto","created_at":"2022-04-13 15:38:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":330188,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1517031/v1/292f11ec-5dbe-4025-b4cd-3ed71490f820.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study","fulltext":[{"header":"Background","content":"\u003cp\u003eA recent study has estimated the 0.5% national prevalence of type 1 diabetes (T1D) among adults in the US, which accounted for 5.6% of all diagnosed diabetes (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). A recent meta-analysis estimated the global prevalence of any diabetic retinopathy (DR) in T1D to be 77% and that of proliferative diabetic retinopathy (PDR) to be 32% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). 4\u0026ndash;12% prevalence of diabetic macular edema (DME) in patients with T1D has been reported (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe number of visual impairment due to DR has decreased during the past decades despite the increasing number of diabetes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). More effective screening for DR, the development of the non-invasive optical coherence tomography (OCT) in the diagnosis of DME, introduction of intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) agents, as well as improvements in the management of diabetes, have been the key factors in the reduction of visual impairment (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003csup\u003e,(7)\u003c/sup\u003e. Lately, DME rather than PDR has been the increasingly common cause of visual impairment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnti-VEGF agents are currently widely used in treatment of DME and considered the first-line treatment in clinically significant DME (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Despite the great number of previous studies evaluating anti-VEGF treatment in DME during the last decade, there are, to our knowledge, no studies reporting the long-term real-world DME treatment outcomes solely in patients with T1D. It has been established that the clinical features and risk factors for DME might vary in patients with T1D from patients with T2D (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of the current descriptive population-based cohort and follow-up of all patients with T1D and DME is to evaluate DME outcomes in a real-world setting and to explore the effect of the choice of treatment (observation, laser, intravitreal anti-VEGF or combination of laser and anti-VEGF) on long-term visual outcomes. Also, the number of intravitreal injections needed to treat DME, and the rate of DME-related visual impairment are studied.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis work was carried out at the Oulu University Hospital. The study followed the tenets of the Declaration of Helsinki and it was conducted with the approval of the Oulu University Hospital Research Committee (175/2016). Involvement of patients or the public in the design, or conduct, or reporting, or dissemination plans of the current research was not appropriate. A written informed consent was obtained from the participants.\u003c/p\u003e \u003cp\u003eThis retrospective population-based cohort study was performed on all adult patients with T1D, who presented at the Oulu University Hospital with DME between June 1, 2006 and Dec 31, 2020. All cases of DME observed or treated by laser, intravitreal anti-VEGF injections or vitrectomy in the area were included in the study. The hospital\u0026rsquo;s electronic patient database was used to search for the patients with DME in T1D by using the ICD-10 (International Classification of Diseases) diagnosis codes for diabetic maculopathy (H36.1) and type 1 diabetes (E10.3). Optical coherence tomography (OCT) was used to demonstrate the intra- or subretinal fluid in the macula, and central retinal thickness\u0026thinsp;\u0026ge;\u0026thinsp;300 \u0026micro;m was considered as clinically significant macular edema. Demographic data was collected and included parameters for age, gender, age at the diabetes onset, duration of the diabetes at the onset of both DR and DME, stage of DR during the onset of DME, treatment of DR and DME (observation, laser, intravitreal treatments, vitrectomy) and the time of the follow-up. The best corrected visual acuity (BCVA) was evaluated routinely by the use of the Snellen chart during the DME treatment and follow-up. The BCVA results were converted to ETDRS (Early Treatment of Diabetic Retinopathy Study)-letters in order to calculate changes in vision. The severity of DR was based on the 5-scale classification system by Finnish Current Care Guidelines of Diabetic Retinopathy (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). For the use of laser or intravitreal treatment, the current protocols, and guidelines of DME treatment were adhered to (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). As a rule, the patients with extrafoveal macular edema located\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026micro;m from the central fovea were either observed or subjected to macular laser depending on the location and amount of intraretinal or subretinal fluid. Those with central macular edema within 500 \u0026micro;m from the fovea were primarily subjected to intravitreal anti-VEGF treatment. The patients were subjected to combination treatment with anti-VEGF and macular laser in cases of subsequent central and extrafoveal edema. The recurrence of DME was considered if there were no intraretinal or subretinal fluid in the macular OCT between the separate episodes of DME. In Finland, bevacizumab is commonly used as the first-line intravitreal drug for DME.\u003c/p\u003e \u003cp\u003eSPSS (IBM Statistical Analysis) version 27.0 was used for the statistical analysis of the data. Summary statistics are presented as mean with standard deviation (SD) unless otherwise stated. Linear mixed model (LLM) was used to compare the change in vision from baseline to the end of follow-up, where patient and eye were set as random effect and sex, age and time from the diagnosis of T1D as adjusting factors. Mean change with a 95% confidence interval is presented as the result of LLM. Two-tailed p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 are considered as statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 206 patients (304 eyes) with T1D and DME were included in the population-based study cohort, out of which 121 (59%) were males. The average age at the time of diagnosis of T1D was 23.4土16.5 years of age (range 1\u0026ndash;79 years). The duration of diabetes at the diagnosis of any DR was 16.4土9.7 years (range 0\u0026ndash;53 years) and that of DME 24.0土11.9 years (range 0\u0026ndash;53 years). The average age of the patients at the onset of DME was 47.4土14.4 years (range 18\u0026ndash;85 years). 155 patients (75%) had non-proliferative DR (NPDR) during the time of diagnosis of DME and only 51 patients (25%) had developed proliferative diabetic retinopathy (PDR). During the study period, there were 304 initial episodes of DME in 206 patients with T1D. Including the recurrences, a total of 456 episodes of DME in 304 eyes of the patients were noted. The average follow-up time of a single patient was 65土45 months (range 4-236 months). There were 18 deaths (9%) among the patients during the 15-year study period. The demographics are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eCharacteristics of the participants.\u003c/div\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003eIn a total of 45 DME episodes (15%) the patients were observed with no treatment for DME. The patients had macular laser treatment in 100 (33%), intravitreal anti-VEGF in 124 (41%) and combination of laser and intravitreal injections in 35 (12%) cases of DME. During the follow-up period between the years 2006\u0026ndash;2020, the use of intravitreal agents has significantly increased after established treatment practices have become more common after the first years of availability of these drugs.\u003c/p\u003e\n\u003cp\u003eAn average baseline BCVA at the time of diagnosis of DME was 76.9土12.5 ETDRS letters (range 15.1\u0026ndash;95.2 ETDRS letters). At the onset of DME, five T1D patients (2.4%) were visually impaired according to classification of visual impairment by the World Health Organization (WHO). However, treatment of DME improved the BCVA in several cases, and at the end of follow-up, only two of these patients (1.0%) met the criteria of visual impairment.\u003c/p\u003e\n\u003cp\u003eAfter the initial DME, there was no significant change in BCVA in the observation group (gain of 0.1 ETDRS letters, p\u0026thinsp;\u0026gt;\u0026thinsp;0.90). A small, 0.4 ETDRS letter decrease was noted in the laser group (p\u0026thinsp;=\u0026thinsp;0.61). Improvements of BCVA of 4.9 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5.5 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) ETDRS letters were documented in the anti-VEGF and combination (anti-VEGF and laser) groups after the preliminary episode of DME, respectively. In addition, patients treated with either anti-VEGF agents alone or in combination with laser, received statistically significant long-term improvements of 4.1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5.1 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) ETDRS letters, respectively. After the follow-up a 3.7 ETDRS letter decrease was documented in the observation group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.90) and a 1.1 (p\u0026thinsp;=\u0026thinsp;0.14) ETDRS letter decline in the laser group of patients. The visual outcomes of the alternative treatments of DME are presented in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Ophthalmological outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003eA great majority, over 99%, of the DME patients treated by intravitreal agents received bevacizumab as a first-line drug. In only a single case (0.6%), aflibercept was used as a primary choice for anti-VEGF treatment. In 15% (n\u0026thinsp;=\u0026thinsp;24) of the cases, the switch from bevacizumab to aflibercept was documented at some phase of the follow-up. An average of 6.1土4.8 injections of either anti-VEGF drug (6.0 in anti-VEGF group and 6.5 in the combination group, range 1\u0026ndash;33) were needed to treat DME, and most injections were emphasized to a first treatment year. None of these patients received intravitreal corticosteroid or underwent vitrectomy.\u003c/p\u003e\n\u003cp\u003eIn just over a third (37%) of the cases, there was only a single episode of DME during the follow-up period (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Depending on the choice of the primary treatment there seems to be differences between the groups in the stability of the treatment outcomes in the terms of the renewal of DME: the recurrence occurred in 91% of the cases in the observation group, 59% of the cases in the laser group, 65% of the cases in the anti-VEGF group and 37% of the cases in the combination group of laser and anti-VEGF during the average follow-up period of 65 months.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe duration of diabetes, poor glycemic control, high blood pressure and proteinuria are known risk factors when observing the development of diabetes related complications (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Globally, DR has been one of the leading causes of blindness among the working age population and the most common complication of T1D (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, the number of visual impairment due to DR has decreased during the past decades (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). More effective screening for DR and improvement in the management of both diabetes and DR have been key factors in the reduction of visual impairment (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Accordingly, DME related visual impairment was rare and reduced in the present study during the 15-year follow-up in a population-based cohort of T1D patients with DME. We might assume that the improvements in both diagnostic accuracy and treatment possibilities of DME during the past 15 years have played an important role in this phenomenon.\u003c/p\u003e \u003cp\u003eWarwick et al. has reported that DME is associated with the duration of diabetes (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In agreement with this, our results showed that in T1D patients DME developed almost 10 years later than the first signs of DR. One may speculate that the prevalence of DME increases along the severity of DR. However, only less than one fourth of the study patients with DME had PDR. Previous study has revealed a high 94% prevalence of any DR and 35% prevalence of PDR in patients with T1D since childhood and duration of T1D for over twenty years (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The T1D patients with DME in the present study differ from this cohort of patients with T1D since childhood, according to older age at the onset of diabetes and the lower prevalence of PDR.\u003c/p\u003e \u003cp\u003eThe treatment for DME has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Laser photocoagulation has been the standard treatment for DME for almost three decades, but currently anti-VEGF agents are considered the first line treatment alternative in center-involving DME (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Several large clinical trials have demonstrated that the improvement of BCVA\u0026thinsp;\u0026gt;\u0026thinsp;15 ETDRS letters has been achieved by anti-VEGF agents in 33\u0026ndash;45% of patients with either type 1 or type 2 diabetes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003csup\u003e,(17)\u003c/sup\u003e. Superior visual outcomes have been reported by ranibizumab treatment compared to treatment performed by laser, and a higher proportion of patients has gained significant\u0026thinsp;\u0026gt;\u0026thinsp;10\u0026ndash;15 ETDRS letter increase in BCVA when treated with anti-VEGF (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Similarly, the BOLT study has revealed that the number of DME patients gaining\u0026thinsp;\u0026gt;\u0026thinsp;15 ETDRS letters was significantly greater when treated with bevacizumab compared to macular laser (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In agreement with these results, DME patients gaining the most ETDRS letters in the current real-world study were treated by bevacizumab and the best long-term visual outcomes were achieved with combination treatment with both anti-VEGF and macular laser. However, previous studies have suggested that DME patients with relatively good BCVA could be observed when BCVA remains stable (\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Our real-world results show, however, a decrease in BCVA in the observation group of patients receiving no treatment in the long term, suggesting that the early treatment of DME might be reasonable to maintain good vision. This is of particular importance when considering the necessity of functional vision for these working-aged, relatively young patients with T1D. Accordingly, the benefits of early intensive treatment by anti-VEGF has recently been shown to result in satisfying long-term visual outcomes (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Even in the cases of no BCVA improvement, anti-VEGF treatment may improve contrast sensitivity in DME patients (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and thus provide the best long-time safety in maintaining good visual function.\u003c/p\u003e \u003cp\u003eBeyond VEGF, the presence of inflammation is known to affect DME pathogenesis and intravitreal corticosteroids may be used to treat DME (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In our T1D patient cohort none of the patients received intravitreal corticosteroids. This might be explained by the known side-effects of corticosteroids, such as cataract development or possible increase in intraocular pressure (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Most study patients, at the average age of 47 years, might be assumed not to have sight-threatening cataract, and the formation of cataract might thus be attempted to avoid by using primarily anti-VEGF drugs classified with a positive safety profile.\u003c/p\u003e \u003cp\u003eThere are some limitations in our study. First, the retrospective nature of the study might affect the assembly of different treatment groups and thus comparison of the outcomes. Understandably, baseline visual acuities varied according to the presence or lack of central-involving edema in the participants, although there were no defined BCVA-level for the choice of each treatment. Taking this into consideration, the intra- but no intergroup analysis in the long-term changes in BCVA were completed. Secondly, the underlying risk factors for DME were only partly available, and precise data of the blood glucose levels, cholesterol and kidney function were lacking. Thirdly, the current data did not include any patients treated with intravitreal corticosteroids and the visual outcomes of that treatment cannot be concluded. We consider the inclusion of only T1D patients with DME as part of the current study as a strength in contrast to most studies that are completed with patients with both type 1 and type 2 diabetes. There are significant differences in the pathogenesis as well as risk factors for DME between these patient groups and combining them might be a possible source of bias. Also, the real-world setting and long-term follow-up of the population-based cohort might be considered as strengths of the present study.\u003c/p\u003e \u003cp\u003eIn conclusion, our results suggest that early intervention of DME by intravitreal anti-VEGF treatment alone or in combination with laser might be beneficial in terms of visual improvement in patients with T1D. Visual acuity slightly decreased or remained stable in those observed or treated with laser, respectively. A low rate of DME recurrences and the beneficial effect on contrast sensitivity (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) highlight the importance of timely anti-VEGF in maintaining good visual function in patients with DME.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDuring the past 15 years, anti-VEGF agents have become the first-line treatment for center-involving DME after laser photocoagulation being the golden standard treatment for DME for almost three decades. Though the benefits of anti-VEGF agents are well-known, the knowledge of long-term visual prognosis of patients with T1D and DME is still lacking.\u003c/p\u003e \u003cp\u003eThis study reports, for the first time, long-term, real-world DME treatment outcomes solely in patients with T1D since the clinical features and risk factors for DME in T1D differ from those of T2D. Early intensive treatment by anti-VEGF alone, or in combination with macular laser, seems to improve visual outcomes and treatment stability the most in T1D patients with DME.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The study followed the tenets of the Declaration of Helsinki and it was conducted with the approval of the Oulu University Hospital Research Committee (175/2016). A \u003cstrong\u003ewritten informed consent\u0026nbsp;\u003c/strong\u003ewas obtained from the participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e \u003cstrong\u003eThe datasets generated during and analyzed during the current study are not publicly available due to confidentiality of data-protected patient information but are available from the corresponding author on reasonable request.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eEach author (JW, AK, PO, JY, TS, NH) has made substantial contributions to the study. NH:\u0026nbsp;Conception of the study, designing the work, data acquisition and analysis, interpretation of the data and writing the manuscript.\u0026nbsp;JW, AK, PO: Design of the work, analysis, and interpretation of the data\u0026nbsp;and substantive revision of the manuscript. JW,\u0026nbsp;JY \u0026amp; TS: Data acquisition, interpretation of the data and substantive revision of the manuscript.\u0026nbsp;All authors have approved the submitted version and agreed both to be personally accountable for their own contributions and to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eXu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018 Sep 4;362:k1497.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eYau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eWarwick AN, Brooks AP, Osmond C, Krishnan R, Medscape. Prevalence of referable, sight-threatening retinopathy in type 1 diabetes and its relationship to diabetes duration and systemic risk factors. Eye. 2017 Feb;31(2):333\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eTeo ZL, Tham Y-C, Yan Yu MC, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology [Internet]. 2021 Apr 30; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.ophtha.2021.04.027\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss [Internet]. Vol.\u0026nbsp;2, Eye and Vision. 2015. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1186/s40662-015-0026-2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMitchell P, Wong TY, Diabetic Macular Edema Treatment Guideline Working Group. Management paradigms for diabetic macular edema. Am J Ophthalmol. 2014 Mar;157(3):505\u0026ndash;13.e1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHautala N, Aikkila R, Korpelainen J, Keskitalo A, Kurikka A, Falck A, et al. Marked reductions in visual impairment due to diabetic retinopathy achieved by efficient screening and timely treatment. Acta Ophthalmol. 2014 Sep;92(6):582\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSchmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U, Gerendas BS, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017 Apr 20;237(4):185\u0026ndash;222.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHainsworth DP, Bebu I, Aiello LP, Sivitz W, Gubitosi-Klug R, Malone J, et al. Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study. Diabetes Care. 2019 May;42(5):875\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eSummanen P, Kallioniemi V, Komulainen J, Eriksson L, Forsvik H, Hietala K, et al. [Update on Current Care Guideline: Diabetic retinopathy]. Duodecim. 2015;131(9):893\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDonaghue KC, Marcovecchio ML, Wadwa RP, Chew EY, Wong TY, Calliari LE, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes. 2018 Oct;19 Suppl 27:262\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKlein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984 Apr;102(4):520\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eThomas RL, Halim S, Gurudas S, Sivaprasad S, Owens DR. IDF Diabetes Atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018. Diabetes Res Clin Pract. 2019 Nov;157:107840.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHautala N, Hannula V, Palosaari T, Ebeling T, Falck A. Prevalence of diabetic retinopathy in young adults with type 1 diabetes since childhood: the Oulu cohort study of diabetic retinopathy [Internet]. Vol.\u0026nbsp;92, Acta Ophthalmologica. 2014. p.\u0026nbsp;749\u0026ndash;52. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1111/aos.12426\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEhlers JP, Yeh S, Maguire MG, Smith JR, Mruthyunjaya P, Jain N, et al. Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology. Ophthalmology [Internet]. 2021 Aug 23; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.ophtha.2021.07.009\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBrowning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol. 2018 Dec;66(12):1736\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eUrias EA, Urias GA, Monickaraj F, McGuire P, Das A. Novel therapeutic targets in diabetic macular edema: Beyond VEGF. Vision Res. 2017 Oct;139:221\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMichaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, et al. A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema (BOLT Study) [Internet]. Vol.\u0026nbsp;117, Ophthalmology. 2010. p.\u0026nbsp;1078\u0026ndash;86.e2. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.ophtha.2010.03.045\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD, et al. A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema [Internet]. Vol.\u0026nbsp;130, Archives of Ophthalmology. 2012. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1001/archophthalmol.2012.393\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBeaulieu WT, Glassman AR, Baker CW, Maguire MG, Johnson CA, Melia M, et al. Effect of Initial Aflibercept, Laser, or Observation on Low-Contrast Visual Acuity in Eyes With Diabetic Macular Edema and Good Vision: Ancillary Study Within a Randomized Clinical Trial. Transl Vis Sci Technol. 2021 Mar 1;10(3):3.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBaker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, et al. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA. 2019 May 21;321(19):1880\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGlassman AR, Baker CW, Beaulieu WT, Bressler NM, Punjabi OS, Stockdale CR, et al. Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Apr 1;138(4):341\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZirpel JJ, Pfister IB, Gerhardt C, Garweg JG. Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland. Graefes Arch Clin Exp Ophthalmol [Internet]. 2021 May 4; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1007/s00417-021-05187-z\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eRittiphairoj T, Mir TA, Li T, Virgili G. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2020 Nov 17;11:CD005656.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Type 1 diabetes, diabetic macular edema, anti-VEGF agents, diabetic retinopathy","lastPublishedDoi":"10.21203/rs.3.rs-1517031/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1517031/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The treatment for diabetic macular edema (DME) has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents. The aim of the current study is to evaluate the real-world visual outcomes of diabetic macular edema (DME) treatment in patients with type 1 diabetes (T1D) in long-term follow-up.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA real-world, descriptive, population-based cohort and follow-up of all patients with T1D and DME in 2006-2020 in 34 communities of the Northern Ostrobothnia Hospital District. The main outcome measures included age, gender, duration of T1D at the onset of DME, stage of retinopathy, treatment of DME (observation, laser, intravitreal treatments, combination), and visual outcomes. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of\u003cstrong\u003e \u003c/strong\u003e304 eyes of 206 T1D patients with DME were included. 75% (n=155) had non-proliferative diabetic retinopathy during the onset of DME. 15% of the cases were observed, 33% had macular laser, 41% intravitreal anti-VEGF and 12% combination of laser and intravitreal injections. Patients in anti-VEGF and in combination groups gained 4.9 and 5.5 ETDRS letters after the initial DME (p\u0026lt;0.001 and p\u0026lt;0.001), and the long-term visual improvements were 4.1 and 5.1 ETDRS letters (p\u0026lt;0.001 and p\u0026lt;0.001), respectively.\u003c/p\u003e\u003cp\u003eThe average of 6.1土4.8 anti-VEGF injections were needed to dry DME. Visual impairment due to DME decreased from 2.4% to 1.0% during15 years.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eEarly intensive treatment by anti-VEGF alone or in combination with macular laser seems to be beneficial in terms of better visual outcomes and treatment stability in T1D patients with DME, whereas a slight decrease in vision was noted in observation or laser groups. Moreover, satisfying long-term visual outcomes were commonly achieved with anti-VEGF treatment in a real-world setting.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-13 15:38:46","doi":"10.21203/rs.3.rs-1517031/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2022-04-12T20:05:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-04-11T06:30:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-04-11T06:19:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2022-04-02T15:05:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a37493f-a66d-4ab0-a141-43ee95872723","owner":[],"postedDate":"April 13th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-06-03T04:44:21+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-13 15:38:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1517031","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1517031","identity":"rs-1517031","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}