September 2010




The flip side of intravitreal injections

by Matt Young EyeWorld Contributing Editor


Anti-VEGF molecule binds VEGF, preventing VEGF action at endothelial receptor

Intravitreous injection through pars plana.

Source for both: Karl Brasse, M.D.; EyeLand Design Network

Intravitreal injections have been popularized as of late due to the growth of new therapies including anti-VEGF treatments. But how much do we know about the side effects of intravitreal injections? Sunir J. Garg, M.D., assistant professor of ophthalmology, Retina Service, Wills Eye Institute, Philadelphia, took a look at these undesirable effects in the online April edition of Current Opinion in Ophthalmology. "Recent reports suggest that intravitreal anti-VEGF injections have a low complication rate," Dr. Garg noted. "Similarly, antimicrobials also have low rates of injection-associated complications."

But given that many of these injections are repeated in patients, it is important to know the risks and avoid them.


Raised IOP is the most common side effect of intravitreal triamcinolone. In one study, 28% of eyes treated with 4 mg of triamcinolone required glaucoma drops at some point during a three-year period, Dr. Garg noted. As IOP normalized on treatment, 71% of eyes discontinued IOP-lowering medications, but 8% still needed them. Interesting statistics continue in other research, where 41.2% of eyes receiving 20 mg of triamcinolone developed IOP of at least 21 mm Hg, Dr. Garg noted, which was clearly concerning. When that dosage was bumped up to 25 mg, the percentage hitting the same IOP went up to 52%. There is a silver lining here. "With most patients, the IOP returned to baseline values 1317 months after initial injection," Dr. Garg noted. Cataract is another concern with such therapy. "Patients should be counseled that lens opacities would likely occur (or progress) even after a single triamcinolone injection," Dr. Garg reported. Surgeons should have much less concern about endophthalmitis. "Retrospective reports indicate a per-injection endophthalmitis risk between zero and 0.87%," Dr. Garg noted. Non-infectious inflammatory endophthalmitis appears to occur at a higher rate, however. "Noninfectious endophthalmitis occurs after 0.59.7% of injections," Dr. Garg noted. "This reaction usually starts 13 days after injection and usually resolves within 12 days without affecting final BCVA [best corrected visual acuity]. If there is any doubt whether the endophthalmitis is infectious, intravitreal antibiotics should be considered. In some eyes, the sterile endophthalmitis may be an inflammatory reaction to the preservative used in some triamcinolone preparations, whereas in others it may be attributed to the triamcinolone particles themselves."

Anti-VEGF treatments

"The tremendous number of anti- VEGF injections being performed has increased interest in reducing the complications associated with these injections," Dr. Garg noted. Happily, those complications are few and far between. "The pivotal trials for ranibizumabRanibizumab versus verteporfin for neovascular age-related macular degeneration (ANCHOR) and Ranibizumab for neovascular age-related macular degeneration (MARINA)demonstrated a low rate of endophthalmitis," Dr. Garg reported. "At year 1, ANCHOR reported a 0.07% per-injection endophthalmitis rate. By year 2 there were only three cases of endophthalmitis out of 5921 injections (0.05%). MARINA and the pivotal trial for pegaptanib (VISION) each reported a 0.05% per-injection rate of presumed endophthalmitis."

John D. Sheppard, M.D., professor of ophthalmology, microbiology, and immunology, Eastern Virginia Medical School, Norfolk, Va., recalled that in some of the earlier studies with Macugen (pegaptanib sodium, OSI Eyetech, Melville, N.Y.), it yielded an "alarming rate of endophthalmitis," which was later avoided by stricter adherence to sterilization in surgical centers, he said. Injections for AMD are now "extremely safe with low complications of endophthalmitis," Dr. Sheppard said. Retinal tears are exceedingly rare with anti-VEGF injections, and the rate for cataract is "likely low," Dr. Garg reported.

Antibiotics, antivirals, & antifungals

Toxicity is an area of serious concern related to intravitreal antibiotic injection. "In a monkey model, intravitreal gentamicin caused cellular damage, ischemia, and necrosis," Dr. Garg noted. "A report of eight patients receiving amikacin and gentamicin revealed that even low doses could be toxic. As such, many physicians have eliminated intraocular gentamicin from their treatment protocols (e.g. from infusion fluids and subconjunctival injections). Amikacin, partly due to microbial spectrum of activity and partly due to toxicity concerns, has largely been supplanted by ceftazidime for intraocular injection to treat endophthalmitis."

Intravitreal ganciclovir, meanwhile, may be helpful for immunocompromised patients suffering from CMV retinitis. "Immunocompromised patients may be at greater risk of developing endophthalmitis," Dr. Garg reported. "However, compiling several studies, there is 0.11% per-injection risk associated with intravitreal antiviralsa rate similar to that seen with anti-VEGF agents." The drug is also well tolerated and non-toxic to the retina, Dr. Garg noted. Intravitreal voriconazole is taking the lead in treatment for fungal endophthalmitis, although there are some risks to consider for its rewards, Dr. Garg suggested. "Numerous case reports reiterate the in-vivo efficacy and safety; however, its short intravitreal half-life (2.5 h) makes adjunctive systemic treatment important," Dr. Garg reported. "Side effects of intraocular voriconazole include transient blurry vision, halos, color perception changes, and visual hallucinations."

Editors' note: Dr. Garg has no financial interests related to this study. Dr. Sheppard has no financial interests related to his comments.

Contact information

Garg: 800-331-6634, Sheppard: 757-622-2200,

The flip side of intravitreal injections The flip side of intravitreal injections
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