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CRYSTAL study shows good results of personalized anti-VEGF treatment regimen in CRVO
Frequent monitoring is key to successful management, according to a study investigator.
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Two-year results of the CRYSTAL study show that an as-needed medication regimen with frequent monitoring can reduce the number of anti-VEGF injections needed to achieve and maintain good anatomic and visual acuity outcomes in central retinal vein occlusion.
According to Michael Larsen, MD, DMSc, member of the CRYSTAL Study Group, “The criteria of the CRYSTAL regimen can be easily transferred into clinical practice.”
The study evaluated an individualized dosing regimen with Lucentis 0.5 mg (ranibizumab, Genentech/Novartis) over 24 months. It was an open-label, single-arm, multicenter study conducted at 86 sites in 18 countries worldwide and included 357 patients, 216 of whom completed the follow-up. Patients received ranibizumab monthly for 3 months and were thereafter monitored on a monthly basis.
“We reinjected patients whenever we saw worsening of the macular edema resulting in VA loss,” Larsen said.
Michael Larsen
Good results with fewer injections
At 24 months, the mean visual gain was 12.9 letters, with almost half of the patients gaining 15 letters or more. Improvement occurred rapidly after initiation of the treatment and remained stable during the follow-up.
“The study included patients with ischemia, foveal and perifoveal, and it was interesting to see that this was not a limiting factor for the benefit of the treatment, nor was the longer duration of CRVO. This is very positive and gives us some interesting information, since in other studies on CRVO ischemia was one of the exclusion criteria,” Larsen said.
There was considerable gain even in patients with visual acuity in the lowest range; in fact, they gained the most, irrespective of disease duration, he said.
The mean number of injections was eight in the first year and five in the second year.
“Eight injections in 12 months is two-thirds of what could have been given on a fixed monthly regimen. This was obtained by PRN with fixed monthly reassessment,” Larsen said. “The CRYSTAL study was a successful test of the posology defined by the European Union’s Summary Medicinal Product Characteristics. The key instruction is to postpone injection if visual acuity has been stable for three consecutive monthly visits. The question that remains is whether there is more vision to gain or if more injections can be gained by adding OCT information to the re-treatment algorithm.”
A breakthrough in CRVO
The study reinforces the argument for an aggressive treatment, meaning either a high number of injections at fixed intervals or intense monitoring of the patient. One-week intervals might be ideal, in an early test cycle, to identify a relapse interval that often repeats itself, according to Larsen. It is not unrealistic in settings with good access to OCT.
“We are going to see a technical breakthrough with OCT being installed not only in hospitals and retina practices but in general ophthalmology and optometry practices, as well as in spectacle outlets. Here in Denmark, opticians offer free fundus screening as an extra service to attract customers. Though there are still bureaucratic barriers to the transmission of the information, this is going to revolutionize eye care and health care in general. We have only seen the beginning of it,” he said.
Studies targeting CRVO as a further indication for anti-VEGF therapy have been important because CRVO was a condition for which no treatment had been available. A lot of patients are now spared the most severe consequences of CRVO, which include vitreous hemorrhage, neovascularization and neovascular glaucoma leading to significant vision loss. Such complications are now rarely seen if patients are treated adequately.
“Sometimes, in our busy clinical practice, we fail to appreciate what a revolution this has been. Ten years ago, there was nothing we could do for patients with CRVO, and they were kept out of the hospitals unless they had neovascular glaucoma. After a while you begin to forget what the natural history of a disease might be,” Larsen said. “There is now a whole new generation of young ophthalmologists who have never seen the natural history of CRVO, and this is how fast things can happen. This is another very good story in modern medicine.” – by Michela Cimberle
- For more information:
- Michael Larsen, MD, DMSc, professor of clinical ophthalmology, can be reached at Department of Ophthalmology, Rigshospitalet-Glostrup, University of Copenhagen, Nordre Ringvej 57, DK-2600 Glostrup, Denmark; email: miclar01@regionh.dk.
Disclosure: Larsen reports he received financial support and/or consulting fees from Novartis, Bayer, Allergan, Roche, QLT, GlaxoSmithKline, AstraZeneca and Novo Nordisk.