Retinal vein occlusion treatment undergoes paradigm shift with pharmacotherapy

Based on findings from a series of clinical trials in recent years, pharmacotherapy has supplanted both laser photocoagulation and a watchful waiting approach as the first-line therapy for retinal vein occlusion.


By Nancy Groves; Reviewed by Szilárd Kiss, MD

New York-A paradigm shift in the treatment of retinal vein occlusion (RVO) means that pharmacotherapy has supplanted the concept of watch and wait and the use of laser photocoagulation as first-line therapy, said Szilárd Kiss, MD.

While retina specialists are likely to follow the new recommendations, general ophthalmologists may not be aware of the changes, which would affect their referrals, said Dr. Kiss, a retina specialist and director of clinical research and associate professor of ophthalmology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York.

“Pharmacotherapy with intravitreal anti-vascular endothelial growth factor (VEGF), whether aflibercept (Eylea, Regeneron), ranibizumab (Lucentis, Genentech), or off-label bevacizumab (Avastin, Genentech) or with a steroid-primarily dexamethasone intravitreal implant (Ozurdex, Allergan)-is the standard of care in 2014,” Dr. Kiss said.

“There really has been a revolution in the treatment of RVO over the past couple of years,” he continued. “Even 3 or 4 years ago, the whole concept of treating RVO was initially watch and wait. If the decreased vision caused by the macular edema secondary to the vein occlusion didn’t spontaneously resolve, treatment was initiated, most often with laser photocoagulation in cases of branch occlusion.”

Understanding the changes

Over the past couple of years, the results of several large, prospective clinical trials have indicated that watchful waiting does a disservice to patients. In 2014, the concept of sending a patient away without treatment is outdated, and laser photocoagulation is no longer a first-line or possibly even second-line treatment for either branch or central RVO, Dr. Kiss noted.


What all the trials showed was that patients who were treated earlier had a better chance of gaining vision. Under the watch-and-wait protocol, the ultimate visual acuity following treatment was not as good as if patients had been treated earlier. While skeptics might counter that pharmaceutical companies sponsored the trials with a vested interest in positive outcomes for treatment using their medications, Dr. Kiss observed that three different companies conducted the trials, yet produced nearly identical results in terms of earlier treatment (Genentech, BRVO and CRUISE trials; Allergan GENEVA trial; Regeneron GALILEO and COPERNICUS trials).

The changed paradigm

As an example of the changed paradigm, Dr. Kiss would treat patients with BRVO, macular edema, and 20/40 vision with an injection at presentation to his clinic rather than sending them off to wait for the edema to resolve on its own. While anti-VEGF therapy is generally the first choice in pharmacotherapy, this treatment does not work for everyone. In some cases, patients may benefit from switching to a steroid or adjunctive treatment with a steroid.

His threshold for an adjustment in treatment is typically after three injections of anti-VEGF therapy. If optical coherence tomography and vision results are not showing improvement at that point, “I will add a steroid, and that steroid is Ozurdex, to see if A, I can get a better vision result; B, if I can get rid of that fluid; and C, if I can decrease the number of anti-VEGF injections I may need,” he said.

Dr. Kiss also cites the work of Michael Singer, MD, of San Antonio, TX, and his colleagues, who showed that combination therapy provides a longer duration of action and perhaps a better result than anti-VEGF therapy alone. (Singer MA, et. al. Effect of combination therapy with bevacizumab and dexamethasone intravitreal implant in patients with retinal vein occlusion. Retina. 2012 Jul;32:1289-1294.)

However, laser therapy may be appropriate in a limited number of patients, such as those who develop neovascularization secondary to CRVO or those who have large areas of ischemia typically found on wide-field angiography.


In cases such as a pseudophakic patient presenting with CRVO, it is almost certain that treatment with one or two anti-VEGF injections will be insufficient. To avoid a large treatment burden, Dr. Kiss will instead initiate combination therapy: an anti-VEGF injection on presentation followed a week or two later by a steroid injection.

He also noted that he and other specialists are likely to veer from the treatment regimen followed in clinical trials, due to concerns about the treatment burden of monthly examinations and injections on patients and caregivers–as well as physicians and the healthcare system. While in clinical trials, patients may average 8 or 9 injections in the first 12 months of treatment, the average is closer to 4 in the practice setting.

However, recent research suggests that patients receiving fewer injections are not achieving the same results in visual acuity gains as were found in the clinical trials, Dr. Kiss said. He added, though, that even with fewer injections, results are generally better than the natural history or those resulting from watchful waiting. (Kiss S, et. al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema. Clin Ophthalmol. 2014 Aug 26;8:1611-1621.)

Work together

“With that being said, injections work, pharmacotherapy works; it’s the first line in treatment and works better than waiting,” Dr. Kiss said.

He acknowledged that the treatment of retinal disorders is changing quickly, and new paradigms such as that for RVO do not always reach busy practitioners quickly.

His message to the comprehensive ophthalmologist is two-fold: if you see a vein occlusion, make sure that the patient receives a systemic workup with a primary-care physician to ensure that diabetes, hypertension, and underlying coagulopathy are addressed, and secondly, promptly refer the patient to a retina specialist.