IOP spikes persist after anti-VEGF injections despite preventive measures

Study author says treatment could still benefit high-risk glaucoma patients.

Ronald E.P. Frenkel

Administering IOP-lowering medication before intravitreal injections of three anti-VEGF agents is not effective in preventing initial IOP increases, according to a study.

The spikes that followed injections of Macugen (pegaptanib, Eyetech/Pfizer), Lucentis (ranibizumab, Genentech) and Avastin (bevacizumab, Genentech) were significant but temporary in most cases.

According to Ronald E.P. Frenkel, MD, corresponding study author, the real concern is the damage that can be inflicted to the optic nerve by repeated increases in IOP.

“We would expect that this may only become evident after many [anti-VEGF] treatments in an individual over months to years,” he told Ocular Surgery News. “However, if a patient has advanced optic nerve damage, then my concern is heightened for the propensity of these significant IOP spikes to damage the nerve.”

Despite the study results, IOP-lowering medication still has a theoretical benefit for patients who have prior optic nerve damage, as well as those with pre-existing glaucoma, Dr. Frenkel said.

The results were published in Archives of Ophthalmology.

Patients, methods

Of the 71 patients included in the retrospective case review, 30 received pegaptanib, 47 received ranibizumab and 42 received bevacizumab; some received a combination of anti-VEGFs and others received only one.

All of the patients had been diagnosed with exudative age-related macular degeneration, and 35 also had glaucoma.

Physicians administered up to two topical IOP-lowering medications 1 hour before injection in 63% of pegaptanib patients, 74% of ranibizumab patients and 66% of bevacizumab patients.

Medications included timolol maleate, brimonidine tartrate, apraclonidine hydrochloride, dorzolamide hydrochloride and brinzolamide. Dr. Frenkel said some patients received 500 mg of oral acetazolamide 2 hours before injection either in addition to or in place of the topical medications.

Although IOP is often measured at least 30 minutes after injection, the current study measured IOP within 1 minute of injection. Physicians also took IOP measurements between 3 minutes and 10 minutes, 11 minutes and 20 minutes, and at 1 week after injection.

Study outcomes

There were significant increases in IOP in the first 2 minutes after injection of all three anti-VEGF agents.

Patients in the pegaptanib group had the highest mean IOP of 38 mm Hg, while ranibizumab yielded a mean IOP of 37.75 mm Hg and bevacizumab yielded 34.88 mm Hg. The mean IOP in all groups was reduced to less than 30 mm Hg within 20 minutes of injection. However, two patients in the pegaptanib group developed no light perception, which normalized following anterior chamber paracentesis.

Physicians should consider performing paracentesis at the time of injection in patients at greater risk for losing light perception and ocular circulation and in those who have significantly damaged optic nerves, Dr. Frenkel said.

“A surgical paracentesis can be performed to allow aqueous to egress from the eye, but it should not be done routinely, as it carries with it additional risks such as endophthalmitis. It must be used judiciously,” he said.

Dr. Frenkel and colleagues conducted an additional analysis that compared glaucoma and non-glaucoma patients who were treated with pegaptanib injections and prophylactic IOP-lowering medication. During the 3-minute to 10-minute interval, the glaucoma patients did better than the non-glaucoma patients.

Although the results suggest that prophylactic IOP-lowering medication could benefit advanced glaucoma patients, Dr. Frenkel said it is another treatment that should be reserved for high-risk patients. He added that, based on the study results, the medication will likely benefit only patients receiving pegaptanib or 0.1 cc of bevacizumab.

Future treatment plans

Dr. Frenkel and colleagues are currently evaluating the long-term effects of post-injection IOP spikes on optic nerve structure and the visual fields of glaucoma patients. They are also conducting further study on oral IOP-lowering medication administered before injection, as well as the timing of prophylactic dosing, he said.

However, Dr. Frenkel noted that physicians must remain cautious when prescribing IOP-lowering medication, not only in terms of patient safety but also in terms of cost to the health care system.

He estimated that about 200,000 people in the United States are receiving anti-VEGF injections annually. If half of them are receiving multiple doses of topical IOP-lowering therapy, often unnecessarily, it could be costing the health care system about $200 million a year, Dr. Frenkel said.

“From both a clinical practice and a cost vantage point, we need to be quite selective as to which patients receive these drops so that we do not waste precious health care dollars,” he said. – by Courtney Preston

Reference:

• Frenkel MP, Haji SA, Frenkel RE. Effect of prophylactic intraocular pressure-lowering medication on intraocular pressure spikes after intravitreal injections. Arch Ophthalmol. 2010;128(12):1523-1527.

• Ronald E.P. Frenkel, MD, can be reached at the East Florida Eye Institute, 509 SE Riverside Drive, Suite 302, Stuart, FL 34994; email: efleye@aol.com.
• Disclosure: Dr. Frenkel has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.

Patients receiving intravitreal injections of anti-VEGF drugs will experience significant spikes in IOP immediately following the injection procedure. These IOP spikes are temporary, with IOP returning to less than 30 mm Hg within 20 minutes in all patients in this report. Unlike in prior studies, the investigators found a similar rate of IOP normalization in eyes with and without glaucoma. The study does not support the prophylactic use of IOP-lowering medications prior to injection, as this intervention did not prevent or shorten the IOP elevations. As we do not yet know whether these transient spikes in IOP cause damage to the eye, clinicians need to weigh the risk and benefits of these injections in patients with glaucoma and compromised optic nerves. A paracentesis or injections of a reduced volume of drug are two strategies that can be considered in eyes judged to be at risk for damage from these IOP spikes.

– K. Bailey Freund, MD
New York
Disclosure: Dr. Freund is on Genentech’s scientific advisory board.