Impact of Pachychoroid and DRIL on the Treatment of Diabetic Macular Oedema with Intravitreal Bevacizumab

Abstract

Purpose To evaluate the long-term outcome of intravitreal bevacizumab in eyes with diabetic macular oedema (DME) following a PRN (pro re nata) regimen. Additionally, we investigated the effect of the presence of disorganisation of the retinal inner layers (DRILs) and pachychoroid (PC) at baseline on clinical outcome.

Methods This retrospective study included 112 naïve eyes with DME that were followed up for 2 years. All eyes were treated with six initial bevacizumab injections at monthly intervals and then received treatment according to a PRN regimen. In case of poor response to bevacizumab, therapy was switched to other agents. Main outcome measures included: best-corrected visual acuity (BCVA), central macular thickness (CMT), and number of intravitreal injections (IVI s). In addition, we examined the effect of the presence of DRILs and PC at baseline on clinical outcome.

Results BVCA improved significantly and CMT decreased significantly during the first 2 years of treatment. The number of IVI s per eye was 11.1 ± 4.8 at the end of the second year. Treatment had to be switched to other agents in 47 eyes (42%). The timing of switching was 12.4 ± 6.1 months after a mean of 9.2 ± 3.3 IVI s. Patients with DRILs at baseline (29.5%) had significantly worse BCVA at all time points before and after treatment, although CMT was significantly lower before treatment and comparable to patients without DRILs during treatment. Patients with PC at baseline (35.7%) had no significant differences in BVCA and CMT at all time points compared with patients without PC.

Conclusions This study demonstrates statistically significant functional and anatomical improvement in patients with DME treated with intravitreal bevacizumab after 2 years. However, more than 40% of eyes required a switch in therapy. The presence of DRILs at baseline had a negative effect whereas the presence of PC at baseline had no effect on clinical outcome.

Zusammenfassung

Hintergrund Ziel der Studie war es, die Langzeitergebnisse der intravitrealen Bevacizumab-Behandlung von Augen mit diabetischem Makulaödem (DME) nach einem PRN (pro re nata) Schema zu untersuchen. Darüber hinaus untersuchten wir die Auswirkung des Vorliegens einer Desorganisation der retinalen Innenschichten (DRIL) und des Pachychoroids (PC) zu Beginn der Studie auf das klinische Ergebnis.

Methoden Diese retrospektive Studie umfasste 112 naive Augen mit DME, die 2 Jahre lang nachbeobachtet wurden. Alle Augen wurden zunächst mit sechs Bevacizumab-Injektionen in monatlichen Abständen behandelt und erhielten anschließend eine Behandlung nach einem PRN-Schema. Bei schlechtem Ansprechen auf Bevacizumab wurde die Therapie auf andere Präparate gewechselt. Zu den Hauptzielgrößen gehörten: bestkorrigierter Visus (BCVA), zentrale Makuladicke (CMT) und die Anzahl der intravitrealen Injektionen (IVI). Darüber hinaus untersuchten wir die Auswirkungen des Vorhandenseins von DRIL und PC bei Studienbeginn auf das klinische Ergebnis.

Ergebnisse In den ersten 2 Jahren der Behandlung verbesserte sich der BVCA signifikant und die CMT ging deutlich zurück. Die Anzahl der IVI pro Auge betrug am Ende des zweiten Jahres 11,1 ± 4,8. Bei 47 Augen (42%) musste die Behandlung auf andere Präparate gewechselt werden. Der Zeitpunkt des Wechsels lag bei 12,4 ± 6,1 Monaten nach durchschnittlich 9,2 ± 3,3 IVI. Patienten mit DRIL zu Studienbeginn (29,5%) hatten zu allen Zeitpunkten vor und nach der Behandlung einen signifikant schlechteren Visus, obwohl die CMT vor der Behandlung signifikant niedriger und während der Behandlung vergleichbar mit Patienten ohne DRIL war. Bei Patienten mit PC zu Behandlungsbeginn (35,7%) gab es zu allen Zeitpunkten keine signifikanten Unterschiede bei BVCA und CMT im Vergleich mit Patienten ohne PC.

Schlussfolgerungen Diese Studie zeigt eine statistisch signifikante funktionelle und anatomische Verbesserung bei Patienten mit DME, die innerhalb von 2 Jahren mit intravitrealem Bevacizumab behandelt wurden. Allerdings war bei mehr als 40 % der Augen ein Therapiewechsel erforderlich. Das Vorhandensein von DRIL bei Studienbeginn hatte einen negativen Effekt, während das Vorhandensein von PC bei Studienbeginn keinen Einfluss auf das klinische Ergebnis hatte.

Conclusion

Already known:

• DME patients showed significant anatomical and functional improvement under intravitreal bevacizumab therapy following a PRN regimen.

• However, more than 40% of eyes had to be switched to another agent.

Newly described:

• The presence of DRILs at baseline led to a worse overall clinical outcome.

• The presence of a PC at baseline did not lead to significant changes in the results.

Key words

retina - DME - DRIL - pachychoroid - bevacizumab

Schlüsselwörter

Retina - DRIL - Pachychoroid - DMÖ - Bevacizumab

Publication History

Received: 18 August 2023

Accepted: 15 December 2023

Article published online:
14 February 2024

• References

• 1 Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond) 2015; 2: 17
• 2 Ding J, Wong TY. Current epidemiology of diabetic retinopathy and diabetic macular edema. Curr Diab Rep 2012; 12: 346-354
• 3 Browning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol 2018; 66: 1736-1750
• 4 Abramoff MD, Fort P, Han IC. et al. Approach for clinically useful comprehensive classification of vascular and neural aspects of diabetic retinal disease. Invest Ophthalmol Vis Sci 2018; 59: 519-527
• 5 Deutsche Ophthalmologische Gesellschaft (DOG), Retinologische Gesellschaft e. V. (RG,, Berufsverband der Augenärzte Deutschlands e. V. (BVA). Stellungnahme der DOG, der RG und des BVA zur Therapie des diabetischen Makulaödems. Klin Monbl Augenheilkd 2020; 237: 325-352
• 6 Schmidt-Erfurth U, Garcia-Arumi J, Bandello F. et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica 2017; 237: 185-222
• 7 Sun JK, Lin MM, Lammer J. et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol 2014; 132: 1309-1316
• 8 Abdin AD, Suffo S, Fries FN. et al. [Uniform classification of the pachychoroid spectrum disorders]. Ophthalmologe 2021; 118: 865-878
• 9 Borooah S, Sim PY, Phatak S. et al. Pachychoroid spectrum disease. Acta Ophthalmol 2021; 99: e806-e822
• 10 Fryczkowski AW, Sato SE, Hodes BL. Changes in the diabetic choroidal vasculature: scanning electron microscopy findings. Ann Ophthalmol 1988; 20: 299-305
• 11 Nourinia R, Ahmadieh H, Nekoei E. et al. Changes in central choroidal thickness after treatment of diabetic macular edema with intravitreal bevacizumab correlation with central macular thickness and best-corrected visual acuity. Retina 2018; 38: 970-975
• 12 Kim JT, Lee DH, Joe SG. et al. Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 2013; 54: 3378-3384
• 13 Adhi M, Brewer E, Waheed NK. et al. Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 2013; 131: 1267-1274
• 14 Esmaeelpour M, Povazay B, Hermann B. et al. Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52: 5311-5316
• 15 Abdin AD, Suffo S, Bischoff-Jung M. et al. [Advantages of a designated IVI center for a German university eye hospital]. Ophthalmologe 2020; 117: 50-57
• 16 Zur D, Iglicki M, Feldinger L. et al. Disorganization of Retinal Inner Layers as a Biomarker for Idiopathic Epiretinal Membrane After Macular Surgery-The DREAM Study. Am J Ophthalmol 2018; 196: 129-135
• 17 Aljundi W, Suffo S, Munteanu C. et al. Intravitreal Injection for Diabetic Macular Edema as Adjunctive Therapy for Proliferative Diabetic Retinopathy: A Retrospective Study. Clin Ophthalmol 2022; 16: 135-143
• 18 Korobelnik JF, Do DV, Schmidt-Erfurth U. et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014; 121: 2247-2254
• 19 Do DV, Schmidt-Erfurth U, Gonzalez VH. et al. The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 2011; 118: 1819-1826
• 20 Massin P, Bandello F, Garweg JG. et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010; 33: 2399-2405
• 21 Schmidt-Erfurth U, Lang GE, Holz FG. et al. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology 2014; 121: 1045-1053
• 22 Bressler SB, Odia I, Glassman AR. et al. Changes in Diabetic Retinopathy Severity When Treating Diabetic Macular Edema with Ranibizumab: DRCR.net Protocol I 5-Year Report. Retina 2018; 38: 1896-1904.2302
• 23 Wells JA, Glassman AR, Ayala AR. et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology 2016; 123: 1351-1359
• 24 Pham B, Thomas SM, Lillie E. et al. Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis. BMJ Open 2019; 9: e022031
• 25 Michaelides M, Kaines A, Hamilton RD. et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 2010; 117: 1078-1086.e2
• 26 Glassman AR, Wells 3rd JA, Josic K. et al. Five-Year Outcomes after initial Aflibercept, Bevacizumab, or Ranibizumab treatment for diabetic macular edema (Protocol T Extension Study). Ophthalmology 2020; 127: 1201-1210
• 27 Busch C, Zur D, Fraser-Bell S. et al. Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema. Acta Diabetol 2018; 55: 789-796
• 28 Rittiphairoj T, Mir TA, Li T. et al. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev 2020; (11) CD005656
• 29 Joltikov KA, Sesi CA, de Castro VM. et al. Disorganization of retinal inner layers (DRIL) and neuroretinal dysfunction in early diabetic retinopathy. Invest Ophthalmol Vis Sci 2018; 59: 5481-5486
• 30 Luís ME, Sampaio F, Costa J. et al. DRIL Influences short-term visual outcome after intravitreal corticosteroid injection for refractory diabetic macular edema. Curr Eye Res 2021; 46: 1378-1386
• 31 Bemme S, Heins A, Lauermann P. et al. Reliability of subjective assessment of spectral-domain OCT pathologic features by multiple raters in retinal vein occlusion. Ophthalmol Sci 2021; 1: 100031
• 32 Dweikat A, Jarrar A, Akkawi M. et al. Baseline subfoveal choroidal thickness as a predictor for response to short-term intravitreal bevacizumab injections in diabetic macular edema. Clin Ophthalmol 2021; 15: 4175-4180
• 33 Rayess N, Rahimy E, Ying GS. et al. Baseline choroidal thickness as a predictor for response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Am J Ophthalmol 2015; 159: 85-91.e1–e3
• 34 Spaide F. The ambiguity of pachychoroid. Retina 2021; 41: 231-237