Figure 10.5  Posterior lens touch with a rupture of the posterior capsule.

General guidelines for intravitreal injections were established for the injecting physician. Some aspects are supported by consensus agreement (use of adequate anesthetic, povidone-iodine, and a lid speculum; dilate the pupil; avoid injecting patients with active eyelid or ocular infection; avoid extensive massage of eyelids; avoid prophylactic or postinjection paracentesis) while other parts have less agreement (e.g., most investigators advocate gloves, most prefer povidone-iodine drops over flush, most use no sterile drape). There is no agreement regarding the use of preor postinjection topical antibiotics, as well as a specific intraocular pressure level that should not be exceeded before the injection.

PHARMACOKINETICS AND CLEARANCE OF INTRAVITREAL DRUGS

The elimination of intravitreal drugs depends on a number of factors. First, the drug may be eliminated via an anterior route passing into

the aqueous humor or a posterior route by active transport across the retina. Zwitterions such as ciprofloxacin and other fluoroquinolones are mainly eliminated by a short elimination half-life through the posterior route. On the other hand, cationic compounds and drugs such as vancomycin and gentamicin show clearing primarily by a passive transport via diffusion in the aqueous humor through the anterior chamber. Second, the mechanism of active transport across the retina is compromised in an inflamed or infected eye. Drugs such as cefazolin that are cleared via the posterior route therefore demonstrated an increased half-life in the vitreous cavity in phakic, nonvitrectomized eyes. Third, the clearance is accelerated in vitrectomized eyes compared to nonvitrectomized eyes, whereas silicone oil-filled eyes show a prolonged elimination of most drugs.

The intravitreal clearance of antibiotics, e.g., 200 µg/0.1 ml moxifloxacin, a fourth-generation fluoroquinolone, was determined to have a half-life of 1.72 hours in rabbit eyes. The mean vitreous concentration was 120.49 + 49.23 µg/ml 1 hour after injection, declining to 20.23 + 5.85 µg/ml at 6 hours and 1.06 + 0.81 µg/ml at 12 hours, respectively.22 The calculated half-life of 400 mg amikacin injected into the vitreous cavity of rabbit eyes was 25.5 hours in phakic control eyes, 14.3 hours in aphakic eyes, and 7.0 hours in aphakic vitrectomized eyes. Inflammation substantially increased the rate of clearance in aphakic eyes.23 Vancomycin hydrochloride 1 mg injected into the mid vitreous cavity of rabbit eyes cleared substantially faster from aphakic-vitrecto- mized eyes (half-life 9.0 hours) compared to aphakic eyes (half-life 8.9 hours) or phakic eyes (half-life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group.

The intravitreal clearance of antibodies such as rituximab, a monoclonal antibody directed against the CD20 B-cell antigen and approved for the treatment of B-cell lymphoma, takes longer.24 The pharmacokinetics of 0.1 ml (1 mg) rituximab following intravitreal administration in rabbit eyes demonstrated in a two-compartment model a clearance from the aqueous humor of 1.2 µl/min and a half-life of 4.7 days. The ocular pharmacokinetics of a 1 mg intravitreal injection of C-14-labeled 5-fluorouracil (5-FU) demonstrated a peak level of 664 µg/ml in phakic nonvitrectomized eye which declines to 7.8 µg/ml at 24 hours. For the aphakic vitrectomized eye comparable values are 669 µg/ml at 0.1 hour and 0.21 µg/ml at 24 hours. 5-FU is cleared more than twice as rapidly