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Follow-up of AMD Patients Treated with Anti-VEGF Therapy: How to Monitor and Decide on Retreatment

Peter K. Kaiser, MD

Cole Eye Institute, Cleveland Clinic


The gold standard of ocular imaging in exudative age-related macular degeneration (AMD) has traditionally been fluorescein angiography (FA). Previous clinical studies assessing treatments for AMD have generally based treatment on the appearance of the choroidal neovascular membrane (CNV) on FA. With the advent of anti-VEGF therapy, our reliance on FA has decreased and physicians are starting to look at other imaging modalities, in particular optical coherence tomography (OCT), to help guide management decisions. Unfortunately, physicians are just learning how to use OCT in AMD and we have little clinical trial data to assist us in deciding when to treat or not treat our patients.


In the past with laser photocoagulation and photodynamic therapy with verteprofin (Visudyne, Novartis, Basil, Switzerland), the Macular Photocoagulation Study (MPS) and Treatment of Age Related Macular Degeneration and Photodynamic Therapy (TAP) Trials gave very strict guidelines when to retreat the patients based on the CNV appearance on FA.1,2 In contrast, the VISION, ANCHOR, and MARINA anti-VEGF trials did not rely on any retreatment criteria during the clinical study, and instead gave injections at either four or six week intervals irrespective of any fluorescein angiographic or other imaging findings.3-5 This leaves clinicians in a quandary since, if we were to follow the strict trial criteria like we did in the past, it would translate into a course of therapy over 24 months with no clinical retreatment criteria. Obviously this is a burden on our patients, clinical practice and health care expenditures. So what are we to do?


Ideally, we would want to look at well-performed clinical studies to help us determine the best modalities to use for retreatment decisions with anti-angiogenic agents. The PrONTO Study used OCT criteria to decide whether a patient should continue to receive ranibizumab (Lucentis, Genentech, South San Francisco, California). In the PrONTO study, patients were retreated if they had evidence of fluid leakage or activity on OCT as well as a few other criteria including evidence of CNV progression on FA. Analysis of the data from this study showed that when there was a change on FA, this change was usually picked up by OCT. More importantly, in the PrONTO Study, patients had a mean improvement in vision and similar visual results as patients receiving monthly dosing of ranibizumab in the MARINA and ANCHOR studies. Therefore, it appears that OCT can be used to successfully manage patients with anti-angiogenic agents. There are several large-scale clinical studies ongoing that may validate the findings of the PrONTO Study, which was a small, uncontrolled study of only 40 patients. Until that time, retreatment decisions based on OCT are still unproven.

Nevertheless, it is my belief that OCT is a very valuable tool for following patients undergoing treatment for neovascular AMD. I currently evaluate the patientís visual acuity, clinical examination including the presence of fluid and hemorrhage, and then evaluate the OCT at every visit. I do not routinely employ FA. If I see evidence of continued activity in the form of decreased vision, hemorrhage or fluid on examination, or intraretinal fluid or cystic spaces on OCT, then I will continue to treat the patient. When the visual acuity has stabilized with no evidence of fluid or hemorrhage clinically and no intraretinal or cystic spaces seen on OCT, I will withhold treatment.

As long as the lesion continues to remain stable, no additional treatment is administered until the patient begins to show evidence of activity using the aforementioned criteria. In our uncontrolled series at the Cole Eye Institute using this regimen, we have found that our visual results are similar to those reported in the MARINA and ANCHOR studies. More importantly, the number of treatments is reduced to approximately five to six treatments per year. It is still too early to tell what will happen in the second year of therapy, that is, whether additional treatment or less treatment will be required.

Thus, I find OCT and good clinical examination are the best tools to follow a patient with AMD being treated with the anti-angiogenic agents available currently. Clinical studies are ongoing to verify these criteria, and I believe these studies will validate the treatment guidelines that we currently use at the Cole Eye Institute.



1. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Arch Ophthalmol, 1999. 117(10): p. 1329-45.

2. Macular Photocoagulation Study Group, Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol, 1982. 100: p. 912-918.

3. Rosenfeld, P.J., et al., Ranibizumab for neovascular age-related macular degeneration. N Engl J Med, 2006. 355(14): p. 1419-31.

4. Gragoudas, E.S., et al., Pegaptanib for neovascular age-related macular degeneration. N Engl J Med, 2004. 351(27): p. 2805-16. 5. Brown, D.M., et al., Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med, 2006. 355(14): p. 1432-44.


Ingrid U. Scott, MD, MPH,  Editor

Professor of Ophthalmology and
Public Health Sciences,
Penn State College of Medicine


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