We noticed you’re blocking ads

Thanks for visiting RetinaToday. Our advertisers are important supporters of this site, and content cannot be accessed if ad-blocking software is activated.

In order to avoid adverse performance issues with this site, please white list https://supplements.retinatoday.com in your ad blocker then refresh this page.

Need help? Click here for instructions.

Digital Supplement | Sponsored by Novartis Pharma AG

Clinical Perspectives on Ranibizumab as a Therapy for All Ages

Prof. Ramin Tadayoni leads a discussion about the clinical management of patients with nAMD, DR, and ROP treated with ranibizumab.

In ROP, is there still room for laser treatment, and what is the maximum number of anti-VEGF injections that can be given?

Prof. Eter: In my practice I prefer not to apply laser treatment in ROP babies. However, if a clinician finds that anti-VEGF treatment is not enough, of course peripheral laser can be added if necessary. In terms of the number of anti-VEGF injections, usually one is enough, but according to the protocol there could be two repeat injections.

In light of the recent approval of ranibizumab for ROP, what practical information can you provide on administering ranibizumab to ROP babies?

Prof. Eter: A different syringe is used to administer ranibizumab to babies compared with adult patients, and the dose is reduced. The injection is performed under general anesthesia, with RetCam (Natus Medical Incorporated) imaging performed before injection. If both eyes are affected, we perform bilateral injections in the same session. Follow-up occurs every 4 days. If treatment is effective, the results are usually apparent within a few days. However, if active disease remains, then another injection is given after about 3 to 4 weeks.

In nAMD, are there any studies showing a benefit of one anti-VEGF agent over another?

Prof. Schlottmann: If you look at the results of the VIEW 1 and 2 studies35 and those of RIVAL,7,8 we see no differences whatsoever regarding VA outcomes, number of injections, development of macular atrophy, safety, or any other major endpoint that you may want to look at. When I discuss this issue with colleagues who tell me that they have seen a difference in the clinic, I tell them that what is statistically significant in a clinical trial can be invisible in clinical practice, and what appears significant in individual clinical practice is often proved to be an anomaly in a large clinical trial.

What is your preferred regimen for treating a patient with nAMD with anti-VEGF therapy?

Prof. Schlottmann: My preferred regimen would be T&E, but it depends on the region the patient comes from since sometimes the payors will not reimburse treatment without an OCT image showing disease activity. That means I have to use a prn regimen in those patients.

Prof. Koh: T&E is also probably my favored regimen. However, not every patient needs such proactive treatment. I usually provide three initial injections if possible, then wait 2 months without treatment. If there is early recurrence of activity, the patient is immediately moved to T&E. If there is no disease recurrence, I give the patient the option of prn but with the proviso that they must be prepared to return every month for review. Most patients can’t or don’t wish to do this, so they choose T&E.

Prof. Eter: In cases of bilateral disease, we use prn, but if it’s just one eye that is being treated, then I prefer T&E.

In DR, are you concerned that injecting an anti-VEGF agent may lead to detachment of the macula?

Prof. Koh: I think there’s always a risk of acceleration of fibrosis and traction, so patients must be counselled appropriately. If anti-VEGF is given, it should be done in the knowledge that the macula may detach and that the patient might require vitrectomy. However, while I wouldn’t say that there is no risk, I do think the risk has been overstated. In the Protocol S study, for example, the rate of tractional retinal detachment was just 5%.21

Could combining anti-VEGF injections with PRP decrease the number of injections required to treat PDR?

Prof. Koh: The results of the PRIDE study suggest that there is no added advantage to combining PRP with anti-VEGF therapy.23,24 In addition, I think it’s wrong to assume that once PRP is done you never have to repeat it again. These patients must still be watched for recurrence of PDR in the future, in the same way that you cannot be complacent after treating PDR with anti-VEGF therapy and say that the disease is gone for good. However, if patients are unable to come back frequently for repeated injections, PRP could potentially be useful—it’s always good to have more than one option.

Conclusions: Ramin Tadayoni

In summary, ranibizumab has been proven to be an effective therapy for retinal diseases across all ages. In babies with retinopathy of prematurity, the RAINBOW study showed that infants treated with ranibizumab 0.2 mg were twice as likely to achieve treatment success versus those treated with laser. In patients of working age, ranibizumab treatment in DR is associated with a reduced risk of DR worsening in eyes with or without PDR. Finally, in older patients with nAMD, the RIVAL study demonstrated comparable clinical outcomes between ranibizumab 0.5 mg and aflibercept 2.0 mg in a T&E regimen. “The wealth of scientific evidence available for ranibizumab has led to seven approved indications and the flexibility in the product label to enable us to meet our patients’ needs, whatever their ages,” said Prof. Tadayoni.


1. Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009;116:57-65 e5.

2. Busbee BG. HARBOR study 12-month outcomes. Data presented at AAO Annual Meeting. October 22-24, 2011. Orlando, FL, USA.

3. Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143:566-583.

4. Silva R, Berta A, Larsen M, et al. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: results with ranibizumab from the TREND Study. Ophthalmology. 2018;125:57-65.

5. Kim LN, Mehta H, Barthelmes D, et al. Metaanalysis of real-world outcomes of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration. Retina. 2016;36:1418-1431.

6. Hatz K, Prunte C. Changing from a pro re nata treatment regimen to a treat and extend regimen with ranibizumab in neovascular age-related macular degeneration. Br J Ophthalmol. 2016;100:1341-1345.

7. Gillies MC, Hunyor AP, Arnold JJ, et al. Effect of ranibizumab and aflibercept on best-corrected visual acuity in treat-and-extend for neovascular age-related macular degeneration: a randomized clinical trial. JAMA Ophthalmol. 2019;137:372-379.

8. Gillies MC, Hunyor AP, Arnold JJ, et al. Macular atrophy in neovascular age-related macular degeneration: a randomized clinical trial comparing ranibizumab and aflibercept (the RIVAL study). Ophthalmology. 2019.

9. International Diabetes Federation. IDF Diabetes Atlas 8th Edition. 2017. Available at: www.diabetesatlas.org. Accessed January 2019.

10. Tremolada G, Del Turco C, Lattanzio R, et al. The role of angiogenesis in the development of proliferative diabetic retinopathy: impact of intravitreal anti-VEGF treatment. Exp Diabetes Res. 2012;2012:728325.

11. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556-564.

12. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98:823-833.

13. Klein R, Klein BE, Moss SE. How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy. Arch Ophthalmol. 2001;119:547-553.

14. Eichenbaum DA. Data presented at American Academy of Optometry. 2017.

15. Park YG, Roh YJ. New diagnostic and therapeutic approaches for preventing the progression of diabetic retinopathy. J Diabetes Res. 2016;2016:1753584.

16. Zhao Y, Singh RP. The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy. Drugs Context. 2018;7:212532.

17. Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight. 2017;2: pii:93751.

18. Wykoff CC, Eichenbaum DA, Roth DB, et al. Ranibizumab induces regression of diabetic retinopathy in most patients at high risk of progression to proliferative diabetic retinopathy. Ophthalmol Retina. 2018;2:997-1009.

19. Ip MS, Domalpally A, Hopkins JJ, et al. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012;130:1145-1152.

20. Gross JG, Glassman AR, Liu D, et al. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136:1138-1148.

21. Gross JG, Glassman AR, Jampol LM, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314:2137-2146.

22. Bressler SB, Qin H, Melia M, et al. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013;131:1033-1040.

23. NCT01594281. Multicenter 12 months clinical study to evaluate efficacy and safety of ranibizumab alone or in combination with laser photocoagulation vs. laser photocoagulation alone in proliferative diabetic retinopathy (PRIDE). Available at: https://clinicaltrials.gov/ct2/show/study/NCT01594281. Accessed October 16, 2019.

24. Liakopoulos S. Data presented at EURETINA. 2018. Vienna, Austria.

25. American Pregnancy Assocation. Premature birth complications. Available at: https://americanpregnancy.org/labor-and-birth/premature-birth-complications/. Accessed August 24, 2019.

26. Ludwig CA, Chen TA, Hernandez-Boussard T, et al. The epidemiology of retinopathy of prematurity in the United States. Ophthalmic Surg Lasers Imaging Retina. 2017;48:553-562.

27. Hakeem AH, Mohamed GB, Othman MF. Retinopathy of prematurity: a study of prevalence and risk factors. Middle East Afr J Ophthalmol. 2012;19:289-294.

28. AAO. Retinopathy of prematurity. Available at: https://eyewiki.aao.org/Retinopathy_of_Prematurity#Aggressive_Posterior_ROP_.28AP-ROP.29. Accessed Aug 24, 2019.

29. Hauspurg AK, Allred EN, Vanderveen DK, et al. Blood gases and retinopathy of prematurity: the ELGAN Study. Neonatology. 2011;99:104-111.

30. Liegl R, Hellstrom A, Smith LE. Retinopathy of prematurity: the need for prevention. Eye Brain. 2016;8:91-102.

31. Mintz-Hittner HA, Kennedy KA, Chuang AZ, et al. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364:603-615.

32. Stahl A, Krohne TU, Eter N, et al. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial. JAMA Pediatr. 2018;172:278-286.

33. Novartis Clinical Trials Results website. https://www.novctrd.com/CtrdWeb/displaypdf.nov?trialresultid=17138 (accessed September 2019).

34. Reynolds J. Data presented at AAO. 2018. Chicago, Illinois, USA.

35. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121:193-201.

Ramin Tadayoni
  • Université Paris 7-Sorbonne Paris Cité, Paris