Synopsis: Replacement of ganciclovir intraocular implants is associated with significant risk.

Source: DF Martin, et al. Ganciclovir implant exchange. Arch Ophthalmol 1997;115:1389-1394.
Investigators at emory university and the National Institutes of Health (NIH) describe their surgical experience with serial implantation of the ganciclovir implant (Vitrasert, Chiron Vision Inc.) in patients with HIV-infection. Patients were participating in a randomized, controlled trial to determine the safety and efficacy of the ganciclovir implant in the treatment of CMV retinitis (DF Martin, et al.Arch Ophthalmol1994;112:1531-1539). Devices were exchanged using the "same-site technique." Based on an estimated ganciclovir release rate of 1 mcg/hr, resulting in depletion of drug from the devices within 32-40 weeks, exchanges were scheduled at 32 weeks or in the event of disease reactivation, whichever occurred first. Fundoscopy was performed every two weeks during the study. Patients did not receive concomitant orally administered ganciclovir.

Twenty-two eyes (10 with active disease) in 15 patients were implanted a second time. Four eyes in four patients, all of whom had inactive disease, received a third implant approximately 32 weeks after the second.

Complications occurred in 7/22 (31.8%) eyes receiving a second implant, only one of which had active disease, including transient vitreous hemorrhage in five eyes (22.7%), a non-infectious anterior uveitis in one (4.5%), and retinal detachment in one (4.5%) (which occurred along the healed border of retinitis 30 days after the exchange procedure). Complications occurred more frequently with the third implantation; dense vitreous hemorrhage occurred in three of four eyes (75%).

Drug assays of the surgically removed implants showed that 8/9 (89%) of the 1-mcg/h devices removed at a median of 31.6 weeks (range, 20-52 weeks) from eyes with active disease were empty. In contrast, 8/13 (62%) 1-mcg/h devices removed at a median of 33.1 weeks (range, 29-37 weeks) from eyes without evidence of reactivation were empty. The estimated mean release rate of ganciclovir was 1.19 mcg/h (range, 0.01-2.62 mcg/h).

Of note, data from the original clinical trial showed that the estimated risk of disease in the fellow eye at six months was 50% and that of biopsy-proven visceral disease was 31%. When first available, this data led to recommendations that orally administered ganciclovir be used as concurrent "prophylactic" therapy in these patients.


As with virtually all therapeutic venues in HIV disease, current practice continues to quickly evolve and adapt to the changing environment of enhanced antiretroviral therapy and the lowered risk of opportunistic infection. When the ganciclovir implant was first used, many retinal surgeons found the same site technique more convenient and hoped it would limit the incidence of future catarrhact formation. It is now believed that repeated use of the same surgical site results in greater organization of the vitreous and retina internally resulting in contraction of tissues, which could increase the long-term risk of retinal detachment. It is also believed that the use of a separate anatomic site is associated with fewer perioperative complications.

Most retinal surgeons therefore currently "replace" an old implant by adding sequential implants to another quadrant. A patient may therefore have up to three implants in each of three quadrants in one eye (the infranasal quadrant is technically more difficult to approach surgically and is therefore seldom used).

The issue of when to "replace" an existing implant has also shifted since the introduction of more highly active antiretroviral therapy. It was initially hoped that the optimal timing for implant exchange could be based on the known duration of drug delivery for these devices. This study, however, demonstrated that drug delivery is quite variable and it is not possible to predict when a device will run out of drug. In addition, while the perioperative risks for implantation are greater in patients with active disease (e.g., retinal detachment) and each subsequent reactivation results in additional retinal damage, the perioperative complications, especially with subsequent implants, and the associated transient loss of vision, which lasts approximately 2-6 weeks, are not insignificant.

More importantly, the risks for reactivation have been greatly reduced by the use of oral ganciclovir for "maintenance therapy" and by the availability of more highly active antiretroviral therapy. In patients living 3-4 years after their initial diagnosis of CMV disease, scheduled replacement of implants every 32 weeks, for example, in the absence of reactivation is no longer recommended, and patients generally receive a new implant (or alternate therapy) only in the event of recurrence. In fact, some HIV experts suggest that ganciclovir maintenance therapy can be foregone in patients who have responded to antiretroviral therapy (e.g., CD4 cells count greater than 300/mm3), even though their existing implant may be outdated. The risks for reactivation in this setting have, however, yet to be determined.

Post intervention, there were statistically significant and substantial reductions in orders for drugs to which pathogens were not susceptible and in orders to which patients were allergic.

a. True

b. False

According to the article by Frank and colleagues, the cost of antibiotics per patient day in the hospital is approximately:

a. $10/d.

b. $15/d.

c. $20/d.

d. $30/d.

e. $2/d.

Which of the following is correct with regard to methicillin-resistant Staphylococcus aureus (MRSA)?

a. MRSA isolates all belong to a single clone.

b. Examination of MRSA strains by phage typing, restriction fragment length polymorphisms produce identical results.

c. The discovery of multiple clones of MRSA has different implications for infection control practices than does long-term persistence of a single strain.

d. MRSA clones are unstable and inevitably disappear within a few months.

Which of the following is correct?

a. Rickettsia conorii is the species most commonly the cause of imported rickettsial infection in North America.

b. R. conorii infection is seldom associated with a tache noire.

c. The tache noire is evidence of dissemination of a rickettsial infection.

d. Ceftriaxone is the antimicrobial of choice in the treatment of infections due to R. conorii.

Which of the following is correct?

a. Ganciclovir intravitreal inserts release the drug at a highly predictable rate.

b. Removal and implantation of a new ganciclovir intravitreal inserts is associated with a high rate of complications.

c. Old ganciclovir intravitreal inserts must be removed before new one can be placed.

d. For reasons not understood, a ganciclovir intravitreal implant in one eye protects the other eye form the development of cytomegalovirus retinitis.