CME

Clinical Advances in the Management of Retinal Vein Occlusion

David M. Brown, MD, FACS

The Methodist Hospital
Retina Consultants of Houston
Houston, Texas

The questions below were submitted by your peers based on a recent CME activity.
The Course Director, Dr. David M. Brown, provides his answers below.

Question 1: Should I investigate my patient with CRVO or BRVO for etiology of this occlusion before commencing treatment? How should I proceed if no cause is found?

Question 2: I have a patient with CRVO who responds well to intravitreal bevacizumab with significant reduction in edema and improvement in vision. But the effect lasts only about 3 weeks. By week 4, vision has dropped, and edema has returned. Is it reasonable to space injections at 3-week intervals rather than 4-week intervals? What is your experience regarding insurance coverage at this shortened interval? Rather than shortening the interval, would there be any benefit to increasing the dose from 1.25 mg (0.05 mL) to 2.5 mg (0.1 mL) or somewhere in between? (Preliminary results from Wu et al. and others suggest no benefit to the increased dose.)

Question 3: My patient has a small BRVO in the papillomacular bundle with visual acuity of 20/25. He has significant fluid (CRT = 445µ on OCT) with heavy ring exudate extending to the margin of foveola with a small cluster of microaneurysms at the edge of foveola also. He has been completely unresponsive to argon grid laser, micropulse 810 nm diode grid laser, subtenons kenalog, intravitreal triesence, and now nine intravitreal bevacizumab injections at monthly intervals. He is a steroid responder, now requiring brimonidine and travoprost to control intraocular pressure. Dexamethasone implant is probably contraindicated due to his previous lack of response on steroid improvement and history of steroid-induced elevated IOP. His BP and lab work-up are normal. Where do we go from here?

Question 4: Have you seen any difference in response between bevacizumab and ranibizumab injections for CRVO? For example, months of aggressive Q4W injections of bevacizumab produce modest improvement in appearance, but central cystic macular edema and poor vision persist. Is there any benefit to switching to ranibizumab?

Should I investigate my patient with CRVO or BRVO for etiology of this occlusion before commencing treatment? How should I proceed if no cause is found?

The decision to institute therapy is independent of the etiology work-up. I generally base my decision of when to treat on the patient’s visual demands. If the RVO is a non-dominant eye and the patient can function with decreased vision for a short period of time, I often observe the patient for 4-8 weeks before recommending therapy (as many patients improve spontaneously). However, in patients who can’t function (eg, truck drivers, professional pilots, law enforcement officers, etc), I often recommend early anti-VEGF therapy. For the laboratory work-up in patients over age 50, I generally only look for major risk factors (diabetes, hypertension). For patients under 50 (or in patients with multiple vascular events), I think it is reasonable to do a work-up looking for predisposition to clotting. If the patients have insurance, I generally refer them to a hematologist for this work-up. It should be noted, however, that this work-up can be very expensive (thousands of dollars), and most of the entities uncovered don’t have any specific treatments other than aspirin therapy. Therefore, in uninsured patients with limited funds, empiric low-dose aspirin therapy could be considered.

I have a patient with CRVO who responds well to intravitreal bevacizumab with significant reduction in edema and improvement in vision. But the effect lasts only about 3 weeks. By week 4, vision has dropped, and edema has returned. Is it reasonable to space injections at 3-week intervals rather than 4-week intervals? What is your experience regarding insurance coverage at this shortened interval? Rather than shortening the interval, would there be any benefit to increasing the dose from 1.25 mg (0.05 mL) to 2.5 mg (0.1 mL) or somewhere in between? (Preliminary results from Wu et al. and others suggest no benefit to the increased dose.)

Although we don’t have study data to support this, I think increasing the dose of anti-VEGF therapy or shortening the time interval between injections will help maintain a normalized anatomy and maintain better visual acuity. I have patients who need injections every 2 weeks. Insurance coverage is really variable and dependent on both the carrier and the geographic area. In Texas, most carriers will only cover one injection per calendar month.

My patient has a small BRVO in the papillomacular bundle with visual acuity of 20/25. He has significant fluid (CRT = 445µ on OCT) with heavy ring exudate extending to the margin of foveola with a small cluster of microaneurysms at the edge of foveola also. He has been completely unresponsive to argon grid laser, micropulse 810 nm diode grid laser, subtenons kenalog, intravitreal triesence, and now nine intravitreal bevacizumab injections at monthly intervals. He is a steroid responder, now requiring brimonidine and travoprost to control intraocular pressure. Dexamethasone implant is probably contraindicated due to his previous lack of response on steroid improvement and history of steroid-induced elevated IOP. His BP and lab work-up are normal. Where do we go from here?

I would consider switching to ranibizumab for several reasons. Some patients seem to have a better response with ranibizumab, and also (although this is certainly off label) you can often give a much larger dose. I generally do an AC tap in a patient if I’m going to give more than .08 mL (especially in a patient with glaucoma). If the retina flattens with this approach, I would probably do several injections followed by focal laser to the microaneurysms.

Have you seen any difference in response between bevacizumab and ranibizumab injections for CRVO? For example, months of aggressive Q4W injections of bevacizumab produce modest improvement in appearance, but central cystic macular edema and poor vision persist. Is there any benefit to switching to ranibizumab?

Most patients do very well with bevacizumab, but some of our bevacizumab “failures” have responded better anatomically with ranibizumab. This may be simply due to variability of the compounding pharmacy or the fact that we often use a higher dose with ranibizumab. I usually try ranibizumab in this type of patient. That being said, really poor visual acuity is generally related to either poor perfusion or degeneration of the neurosensory retina from chronic edema, which may not improve even if the anatomic cysts are eliminated.