How to Overcome Common Challenges in Managing Patients With Retinal Disorders: Looking to the Latest Evidence for Answers

Course Director

Carl Regillo, MD

Carl Regillo, MD
Thomas Jefferson University
Wills Eye Hospital
Philadelphia, Pennsylvania

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Part 2 of a 2-part series

Dr. Regillo provides expert feedback to the questions submitted by your peers during a recent survey on this topic.


The latest treatment advances in managing retinal disorders offer promise for improving patient outcomes and allowing for better therapeutic individualization. However, rapid advances make it difficult for clinicians to remain current on the latest evidence and implications for clinical practice. In this activity, Dr. Carl Regillo explores recent data for various retinal diseases and provides answers for common practical questions and challenges.


This activity is supported by an educational grant from Regeneron Pharmaceuticals.
Additional support provided by Penn State College of Medicine and Answers in CME.

Course Director
Carl Regillo, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Allergan, Inc.; Genentech, Inc.; GlaxoSmithKline; Novartis Corporation; and Regeneron Pharmaceuticals, Inc.
Grant/Research Support from Allergan, Inc.; Genentech, Inc.; GlaxoSmithKline; and Regeneron Pharmaceuticals, Inc.
Speakers Bureau participant with Genentech, Inc. and Regeneron Pharmaceuticals, Inc.
Medical Director
Kadrin Wilfong, MD
Answers in CME, Inc.
Kadrin Wilfong, MD, currently has no financial interests/relationships or affiliations in relation to this activity.

Answers in CME staff who may potentially review content for this activity have disclosed no relevant financial relationships.

Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.

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What are the benefits and limitations of the treat-and-extend and treat-and observe protocols in the management of patients with age-related macular degeneration (AMD)? Should the approach be individualized for each patient?

Dr. Regillo: The treat-and-extend and treat-and-observe approaches are, by definition, a way to individualize anti-VEGF therapy to treat patients with wet AMD. The treat-and-extend has become the more popular regimen used over the years, because for each patient you find that [treatment] interval that seems to work best, but you're treating at every visit so you hope to minimize recurrences and keep the visual gains optimally high. It is more convenient than a frequent-and-fixed regimen, and it may be also more convenient for patients compared to a treat-and-observe protocol because the treat-and-observe does require very frequent follow-up for our patients to keep on top of the disease and identify those recurrences when they do occur. So the treat-and-extend does help to minimize the cost burden of follow up and management of follow up, and for all those reasons has become the preferred technique for retina specialists in the United States over the past few years.

That being said, the potential advantage of a treat-and-observe, or PRN [pro re nata; as needed], approach compared to treat-and-extend or even continuous therapy of any type is that it does allow you to identify the occasional patient who does not need ongoing therapy. Therefore, it effectively becomes the most cost-effective approach, because you don't continue to treat. But you still need to observe those patients closely, so there is still the burden of the patient coming to the office on a regular and frequent basis.

Some major clinical studies, such as the [US] CATT trial1,2 or the IVAN3 study out of the UK, do show that, on average, PRN therapy, which is the treat-and-observe approach, as a way to individualize therapy for wet AMD does tend to result in visual acuity outcomes that aren't quite as good as continuous monthly therapy with ranibizumab, as was used in these studies, or even bevacizumab.
So, over time, the treat-and-observe approach may in some patients be suboptimal. And why is that the case? Well, because when you treat-and-observe, you're effectively allowing for recurrences to take place, and that could translate into some setbacks that a patient may not fully recover from over time. So over the long run, multiple recurrences could mean [irreversible] progression of disease and, therefore, a loss of visual gains that may have been achieved early on in the course of therapy.

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What would be the optimal approach to management of a patient with newly diagnosed nonischemic central retinal vein occlusion (CRVO)? Are there any benefits to early versus delayed treatment initiation?

Dr. Regillo: The optimal approach to managing a patient with a newly diagnosed, nonischemic central retinal vein occlusion is the use of anti-VEGF agents to treat the associated macular edema, which is highly likely to be the source for most, if not all, the decreased acuity in this setting. So, anti-VEGF therapy in the form of FDA-approved ranibizumab or aflibercept for CRVO-related edema works very well.4,5

Frequent treatment upfront will typically reduce the edema and improve the visual acuity. And the respective studies for these two drugs [ie, CRUISE for ranibizumab and COPERNICUS for aflibercept] both point to importance of early detection and early initiation of treatment.6-9 There is a difference in terms of the outcome: [When] initiating treatment early after the onset of the edema from any vein occlusion, central or branch, the results are better. If there is delay of even just a few months, the visual-acuity outcomes may not be as good even if you can eliminate the edema, as was shown in the PRN phase, the last six months of the one-year studies with aflibercept and ranibizumab.

So, at this time, when there is significant decreased vision from macular edema in the setting of a CRVO, it is probably best to initiate treatment sooner rather than later. We do know that, of course, central retinal vein occlusions can occasionally get better.

Narrator: If the CRVO does improve after initiating treatment, Dr. Regillo would consider either extending the treatment interval or even stopping treatment as some of these patients may not need ongoing therapy over the long term.

Dr. Regillo: Certainly if the patient presents with very mild features of central retinal vein occlusion with very mild edema, and relatively good visual acuity, it's certainly reasonable to consider watching and waiting, but that should be done very cautiously and with close follow up. 

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Can anti-VEGF therapy trigger geographic atrophy (GA)? What can be concluded based on current evidence?

Dr. Regillo: This is an important question. We know we can control the neovascular manifestations of macular degeneration very effectively with ongoing anti-VEGF therapy. In the anti-VEGF treatment trials, there have been some hints that patients may lose vision over time from the progression of atrophy in the setting of their wet AMD.

So this question has been raised and it is a concern. Essentially, there is a red flag based on some clinical studies, including the CATT study.1,2 The CATT study did show some increased rates of atrophy in patients who were getting more frequent anti-VEGF therapy. So this is something that is going to be closely scrutinized with longer follow-up in studies going forward. But at this time, we cannot say conclusively that anti-VEGF therapy promotes geographic atrophy or in some way contributes to it. It could very well be that this is the natural course of the dry component of the AMD, while we are in essence [simultaneously] treating the wet component with the anti-VEGF therapy.

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  1. Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group et al. Ophthalmology. 2012;119:1388-1398.
  2. Ziemssen F, Sobolewska B. Drugs Aging. 2011;28:853-865.
  3. IVAN Study Investigators et al. Ophthalmology. 2012;119:1399-1411.
  4. LUCENTIS (ranibizumab injection) Prescribing Information. Accessed November 23, 2013.
  5. EYLEA (aflibercept) Prescribing Information. Accessed November 23, 2013.
  6. Campochiaro PA et al. Ophthalmology. 2011;118:2041-2049.
  7. Boyer D et al. Ophthalmology. 2012;119:1024-1032.
  8. Campochiaro et al. Ophthalmology. 2011;118:2041-2049.
  9. Brown et al. Am J Ophthalmol. 2013;155:429-437.

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Regeneron Pharmaceuticals

This activity is supported by an educational grant from Regeneron Pharmaceuticals.
Additional support provided by Penn State College of Medicine and Answers in CME.

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Q&A: Implications of the Latest Data for Management of Patients With Retinal Diseases

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