Subfoveal choroidal thickness as a predictor of central serous chorioretinopathy.

PurposeThe purpose of the study was to evaluate the role of subfoveal choroidal thickness (CT) measurements as a predictor for the course of central serous chorioretinopathy (CSC).Patients and methodsThirty-eight eyes of 33 patients with CSC were analyzed retrospectively. Key inclusion criteria were naive (acute or recurrent) CSC; a minimum of 12 months of follow up; and the availability of good quality enhanced depth imaging SD-OCT images at each visit. Eyes with changes suggestive of chronic CSC and history of any treatment were excluded. Collected data included demographic profile, visual acuity, subfoveal CT, central macular thickness (CMT), and treatment details. Univariate and multivariate analyses for association of baseline features with need for treatment were performed. On the basis of results of this analysis, the 38 eyes were divided into two groups: Group A (subfoveal CT≤356 µm) and Group B (subfoveal CT>356 µm).ResultsOn univariate analysis, the need for treatment had significantly positive correlation with duration of symptoms (P=0.02), negative correlation with the baseline CT (P<0.01), and no significant correlation with CMT (P=0.13). On multivariate regression analysis, only baseline CT had a statistically significant association with the need for treatment (odds ratio (OR), 0.989; CI, 0.979-0.999; P=0.048). Group A eyes were more likely to require treatment (Group A: 54.55%, 12 of 22 eyes; Group B: 18.75%, 3 of 16 eyes; OR: 5.2, 95% CI, 1.15-23.54; P=0.04). There was a significant decrease in subfoveal CT in Group B (-105.62±108.91 µm; P=0.002).ConclusionCSC with a subfoveal CT≤356 µm is of chronic nature and is more likely to require treatment rather than observation.

Dexamethasone implant in diabetic macular edema in real-life situations.

PURPOSE: To report outcome of eyes with recalcitrant and naive eyes with diabetic macular edema (DME) treated with intravitreal dexamethasone implants (Ozurdex) injection. METHODS: Retrospective multicenter data analysis of eyes with DME treated with Ozurdex implant and with minimum follow-up of at least one year after the first implant. Data collected included demographic details, history of presenting illness, past treatment history, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Paired sample t-test was used to measure mean differences between pre- and post-implant values obtained at baseline and last follow-up. RESULTS: A total of 79 eyes (62 subjects) were included. Sixty-four eyes had been previously treated; 15 eyes were naive. Among the previously treated eyes, mean interval between first Ozurdex injection and any previous treatment was 7.69±8.2 months. In naive eyes, the visual acuity improved from baseline 0.58±0.25 to 0.44±0.33 logMAR at last follow-up (P=0.05). In eyes that had been previously treated, the improvement was from 0.65±0.34 at baseline to 0.48±0.35 logMAR (P=0.01). Mean treatment-free interval was 6.5±4.5 months. Nine eyes were steroid responder with controlled intraocular pressure (IOP), none showed any spike in IOP during the follow-up period. CONCLUSIONS: Ozurdex implant could be a good alternative for recalcitrant as well as naive eyes with DME. The visual gain after initial implant injection was fairly maintained, with additional treatment usually after 6 months in naive eyes. Ozurdex appeared safe even in steroid responders with good control of IOP with antiglaucoma medications.

Retinal detachment.

RD is a serious and well-known complication after cataract surgery, developing in 1% to 3% of all patients undergoing cataract extraction. High myopia, disruption of the posterior capsule intraoperatively or postoperatively by Nd: YAG laser, and vitreous loss increases the risk for RD. Retinal evaluation with detailed indirect ophthalmoscopy with scleral indentation and prophylactic treatment to all lesions that contribute to retinal tear and RD is strongly advocated before cataract surgery and Nd: YAG laser capsulotomy. Intraoperative vitreous loss should be managed meticulously, and these patients should be examined more frequently in the postoperative period. During phacoemulsification, no attempts should be made to retrieve the dislocated nuclear fragments without proper vitrectomy. It is best advised that a vitreoretinal surgeon handles the complication. Early recognition and prompt treatment following the detachment can result in good visual recovery.

Intraocular cilia associated with perforating injury.

PURPOSE: To report a case series of penetrating injury complicated by occurrence of intraocular cilia. METHODS: Retrospective analysis of charts of 11 eyes of 11 patients with penetrating injury and intraocular cilia, presenting between September 1978 and November 1998. Ten eyes underwent surgery for trauma-related problems such as cataract, vitritis, retinal detachment etc., at which time intraocular cilia were removed. One eye did not have surgery and continues to harbour cilia at the posterior perforation site. RESULTS: Metallic wire was responsible for injury in 6 of 11 eyes with intraocular cilia. Five eyes had significant intraocular inflammation. The cilia were located in the anterior segment in 4 eyes; in the posterior segment in 6 eyes and in both in one eye. At the last follow up, 72.7% had 6/18 or better vision. Poor vision in the rest was due to recurrent retinal detachment (2 eyes) and macular scarring (1 eye). CONCLUSION: Intraocular cilia are more commonly associated with injury by a metallic wire. The presentation and management of an injured eye does not seem to be influenced by the presence of cilia in the eye.

A multicentered clinical study of serum as adjuvant therapy for surgical treatment of macular holes. Vitrectomy for Macular Hole Study Group.

OBJECTIVE: To evaluate and compare the risks and benefits of autologous serum as an adjuvant therapy in macular hole surgery for stage 3 or 4 macular holes. METHODS: Comparison of 2 consecutive (nonrandomized) cohorts using standardized methods for the determination of hole size and for surgical procedures, and using the same study surgeons. The serum cohort consisted of 106 eyes using autologous serum as an adjuvant, and the no serum cohort consisted of 58 eyes without adjuvants. The primary end point was the closure of the macular hole as determined by the 6-month fundus photographs. Secondary end points included the number and types of postoperative complications. Comparison in outcomes between the 2 cohorts used chi2 and logistic regression procedures, adjusting for preoperative differences between the study cohorts. RESULTS: At 6 months, the (unadjusted) rate of hole closure was significantly greater for the eyes treated with serum than for the eyes not treated with serum (90 [85%] of 106 vs. 40 [69%] of 58, P = .04). However, after adjusting for preoperative differences in hole diameter and the prevalence of epiretinal membranes, no overall difference in hole closure rates due to serum was found (P = .44). In contrast, benefit due to serum for large holes (diameter >573 microm) was seen (12 [75%] of 16 vs 13 [57%] of 23, P = .04). No differences in complication rates were found between the cohorts. CONCLUSIONS: Any beneficial effect of serum used as an adjuvant to macular hole surgery is small, and, if present, the beneficial effect may be limited to larger holes. A randomized, prospective, controlled study in larger macular holes is needed.

Fluorophotometry in patients with human immunodeficiency virus with and without cytomegalovirus retinitis.

OBJECTIVE: To study the aqueous humor dynamics in subjects with human immunodeficiency virus (HIV) with and without cytomegalovirus (CMV) retinitis. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fourteen HIV-positive subjects (27 eyes, 19 with CMV retinitis and 8 without CMV retinitis), and a control group of 9 HIV-negative subjects (17 eyes). TESTING: Fluorophotometry. MAIN OUTCOME MEASURES: Aqueous flow rates as measured by fluorophotometry and intraocular pressure (IOP). RESULTS: Analysis of variance of the mean corrected aqueous flow rate revealed that both HIV-positive groups had significantly lower aqueous flow rates than did the control group (P < 0.03). No difference in mean aqueous flow rates was found between the HIV-positive eyes with or without CMV retinitis. Comparison of mean IOP revealed that HIV-positive eyes with CMV retinitis had significantly lower IOP than did the HIV-positive eyes without CMV retinitis (P = 0.03) and HIV-negative subjects (P = 0.002). There was no correlation between aqueous flow rate and IOP in HIV-positive subjects (P > 0.5). CONCLUSION: The lack of correlation between the aqueous flow rate and IOP suggests that there may be some disassociation between these parameters in HIV-positive patients. Further studies are needed to better understand the mechanism of aqueous formation and in the management of disorders affecting IOP in this population.

The utility of entoptic perimetry as a screening test for cytomegalovirus retinitis.

OBJECTIVE: To determine the sensitivity and specificity of entoptic perimetry as a noninvasive test for detecting retinal damage due to peripheral cytomegalovirus (CMV) retinitis. DESIGN: A masked study comparing entoptic perimetry with fundus photography under 4 experimental conditions (determined by increasing pixel sizes) on 2 separate testing sessions. SETTING: Acquired immunodeficiency syndrome Ocular Research Unit at the University of California, San Diego. PATIENTS: Twenty-four human immunodeficiency virus-positive and 8 human immunodeficiency virus-negative subjects; 21 eyes with documented CMV retinitis, and 26 eyes that were retinitis free. MEASUREMENTS: For each testing session, screening method, and condition, the presence of CMV retinitis was determined for each meridian (i.e., clock hour), each quadrant (consisting of 3 meridians), and each eye (consisting of all meridians); the amount of retinitis was defined as the percentage of meridians or quadrants with CMV retinitis. RESULTS: Entoptic perimetry was as sensitive and specific as fundus photography in determining the presence of CMV retinitis. Determination of the amount of CMV retinitis tended to be underestimated by perimetry for larger pixel sizes. CONCLUSION: Entoptic perimetry may be an effective and inexpensive alternative to fundus photography for CMV retinitis in hospitals and community clinics.

Effects of topical and subconjunctival cidofovir (HPMPC) in an animal model.

PURPOSE: To characterize the anterior segment effects of cidofovir, using an animal model. METHODS: Cidofovir drops, at concentrations of 0.04%, 0.4% and 4%, were instilled in eyes of guinea pigs once daily for 10 days. Fellow eyes (controls) received normal saline. The corneal epithelium was debrided at day one and then at every other day for 10 days. Subconjunctival injections of 20 microl of 4% cidofovir were given in another group of animals. A micromanometer was used to determine the intraocular pressure (IOP). Eyes were studied histopathologically at the conclusion of the study. RESULTS: There was no significant drop in IOP after 10 days, using the 0.04% concentration of cidofovir drops. Histology revealed mild corneal edema and inflammatory infiltrate; iris, ciliary body and retina were normal. There was a statistically significant drop in IOP in the eyes treated with 0.4% and 4.0% cidofovir eye drops at 10 days (p = 0.005 and p < 0.0001, respectively) compared to baseline. Morphological changes included moderate to severe corneal edema, vascularization and inflammatory infiltration. The iris and ciliary body revealed mild inflammatory changes only at the 4% cidofovir dose. No changes were seen in the retina with any doses. No change in IOP was observed following subconjunctival injections of 4% cidofovir, and histologically, only localized inflammatory changes in the conjunctiva were observed. CONCLUSIONS: The IOP-decreasing effect of cidofovir occurs at doses below those causing intraocular inflammation and is likely due to an effect on the anterior segment. The anterior segment effects of cidofovir in guinea pigs were similar to those in humans. Thus, the guinea pig appears to be a good animal model for studying the effects of cidofovir on the anterior segment structures.

Management of glass intraocular foreign bodies.

PURPOSE: To describe the results of management of glass intraocular foreign bodies (IOFBs). METHODS: A total of 51 eyes of 43 patients that sustained penetrating injury with glass IOFB were studied retrospectively. A total of 23.5% had IOFB only in the anterior segment; the rest had IOFB in the posterior segment alone or in both the anterior and posterior segments. Six eyes were followed conservatively despite IOFB in a functional eye. Removal of IOFB was combined with repair of retinal detachment (where present) using internal tamponade with gas or silicone oil or buckle. RESULTS: After a mean follow-up of 16.8 months, 66.7% of eyes recovered better than 6/60 (20/200) vision and 75.6% had attached retina. On univariate analysis, scleral entry wound, posterior segment IOFB, larger size of IOFB, and retinal damage were found to be associated with poor anatomic outcome. Lower presenting visual acuity, hyphema, retinal damage, subretinal hemorrhage, detached retina, and larger IOFB were associated with a poor functional result. Multivariate analysis identified retinal damage caused by the foreign body as the only factor significantly associated with poor anatomic as well as functional outcome. CONCLUSIONS: Glass IOFBs are caused in a majority of cases by blast injury. Bilaterality is not uncommon. Presence of retinal damage is predictive of poor functional and anatomic results. Overall results are modest with modern vitreoretinal surgical techniques.

Influence of intravitreal injections of HPMPC and related nucleoside analogues on intraocular pressure in guinea pig eyes.

PURPOSE: Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In humans, its dose-limiting intravitreal toxicity results in the lowering of intraocular pressure (IOP). The purpose of the present study was to determine the effects of HPMPC and various acyclic nucleoside phosphonate (ANP) analogues when administered intravitreally in guinea pig eyes and to establish the structural and functional relation of these compounds in connection with their effects on the ciliary body and retina. METHODS: Ninety-six guinea pig eyes were injected with various doses of HPMPC and ANP analogues. RESULTS: Severe lowering of IOP with structural alterations of the ciliary body was observed when doses were administered that achieved final intravitreal concentrations greater than 25 microg/ml HPMPC, 200 microg/ml cyclic HPMPC (cHPMPC), 25 microg/ml (S)-HPMPA, and 625 microg/ml PMEG. Concentrations of 25 microg/ml HPMPC, 200 microg/ml cHPMPC or less, and all concentrations of (R)-HPMPA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA, and (S)-PMPA did not lower IOP significantly, nor did they cause significant histologic changes. CONCLUSIONS: Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti-human cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV compound of the PME series, is toxic at higher doses. Further evaluation of lower doses is needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV activities. The IOP-lowering effect of these compounds appears to be associated with an effect on the ciliary body.

Simultaneous indocyanine green and fluorescein angiography using a confocal scanning laser ophthalmoscope.

BACKGROUND: Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections. METHODS: We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients. RESULTS: There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed. CONCLUSIONS: Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.

The effect of deep posterior subtenon injection of corticosteroids on intraocular pressure.

PURPOSE: To investigate the effect of posterior subtenon injections of corticosteroids on intraocular pressure in a variety of ocular diseases. METHODS: We retrospectively analyzed 202 consecutive posterior subtenon corticosteroid injections (148 of methylprednisolone acetate, 80 mg, and 54 of triamcinolone acetonide, 40 mg) in 63 eyes of 55 patients (26 male, 29 female; mean age +/- SD, 60.17 +/- 26.55 years). All patients had received topical or systemic corticosteroids before the injection, and no rise in intraocular pressure had been noted. Preinjection and postinjection intraocular pressure measurements were compared by two-tailed paired t test. Statistical analysis was performed separately by patient (first injection of first injected eye), by eye (first injection of each eye), and by all injections. To detect increase in intraocular pressure during follow-up, statistical analysis was performed separately 14 to 90 days, 91 to 150 days, and 151 to 270 days after injection. RESULTS: No statistically significant difference was found between preinjection and postinjection intraocular pressure measurements. A power calculation in the most stringent subanalysis (by patient) proved that there is only a 3.87% chance to statistically miss a clinically significant rise in intraocular pressure from 15 to 21 mm Hg. CONCLUSIONS: Posterior subtenon injection of corticosteroids does not cause an increase in intraocular pressure. All patients in our study had been treated previously with topical or systemic corticosteroids and did not react with an excessive increase in intraocular pressure. This safety of repository corticosteroids may therefore not apply to patients whose status in responding to corticosteroids is not known.

Adverse events and autopsy findings after intravitreous cidofovir (HPMPC) therapy in patients with acquired immune deficiency syndrome (AIDS).

OBJECTIVE: The purpose of the study is to evaluate the adverse events and autopsy findings in a series of consecutive 20-microg intravitreous cidofovir injections at a single institution. DESIGN: The study design was a nonrandomized, consecutive case series. PARTICIPANTS: Seventy-six patients with acquired immune deficiency syndrome with cytomegalovirus retinitis were studied prospectively. Sixty-three patients had 1 month's follow-up or longer, and this comprised the study group. In addition, histopathologic findings from 18 eyes of 9 patients were studied at autopsy. INTERVENTION: A total of 296 injections of 20 microg cidofovir were given in 115 eyes. Sixty-three patients who had 246 injections in 93 eyes had 1 month's follow-up or longer for the evaluation of adverse events. MAIN OUTCOME MEASURES: Postinjection chronic hypotony associated with permanent visual loss, transient hypotony, iritis, and its long-term sequela (posterior synechia and cataract, retinal detachment, extraocular cytomegalovirus involvement) were the outcomes of interest in this study. Additionally, light and electron microscopic studies of human eyes were performed. RESULTS: The most severe adverse event was postinjection chronic hypotony. This phenomenon was associated with permanent visual loss. This was observed in 1% of the injections and 3% of the eyes of the patients (95% confidence interval, 0%-6%). Transient hypotony associated with mild-to-moderate visual loss developed in 14%, but vision recovered to baseline levels in these eyes subsequently. Analysis showed that transient hypotony in the injected eye could predict postinjection chronic hypotony in the fellow eye (two-tailed Fisher's exact test, P = 0.02). The incidence of iritis was 32%; posterior synechia and cataract were the long-term sequela of the iritis and developed in 19% and 11% of the eyes, respectively. The incidence of retinal detachment was lower (6%). Histopathologic evaluation of the eyes showed mild-to-moderate atrophy of the nonpigmented epithelium of the ciliary body and no other evidence of intraocular toxicity. CONCLUSIONS: The most serious adverse event was postinjection chronic hypotony, which occurred in 3% of eyes. Episodes of transient hypotony appear to indicate that the fellow eye was predisposed to chronic hypotony. Therefore, it may be prudent to give intravitreous injections at least 2 weeks apart in the fellow eye to evaluate the clinical response of the injected eye.

Vision-threatening complications of surgery for full-thickness macular holes. Vitrectomy for Macular Hole Study Group.

OBJECTIVE: To study complications of vitrectomy surgery for full-thickness macular holes. DESIGN: A multicentered, randomized, controlled clinical trial. PARTICIPANTS: Community and university-based ophthalmology clinics. INTERVENTION: Standardized macular hole surgery versus observation. MAIN OUTCOME MEASURES: Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. RESULTS: Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P < 0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P < 0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P < 0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs. CONCLUSIONS: The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

Intraocular pressure and aqueous humor dynamics in patients with AIDS treated with intravitreal cidofovir (HPMPC) for cytomegalovirus retinitis.

PURPOSE: To evaluate the decrease in intraocular pressure associated with cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections. METHODS: We followed up 97 eyes of 63 patients with acquired immunodeficiency syndrome (AIDS) who had cytomegalovirus retinitis and had been treated with up to nine 20-microgram intravitreal cidofovir injections. Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks after injections. Anterior chamber fluorophotometry was studied in seven eyes (four patients) before and after injections. Ciliary body anatomy was evaluated in two patients. RESULTS: After the first intravitreal injection, mean intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks (P < .001) and 1.3 mm Hg lower than at baseline at 5 to 6 weeks (P = .0025). After the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks (P = .0013) and 1.5 mm Hg lower at 5 to 6 weeks (P = .043). After subsequent injections, however, the decrease was less than 1 mm Hg, suggesting that a plateau had been reached. Pressure in eyes with anterior uveitis after the first injection was lower than that in eyes without anterior uveitis (P < .0001). The mean rate of aqueous flow decreased from 2.8 to 1.9 microliters per minute 2 to 4 weeks after injection (P < .015). Ultrasound biomicroscopy disclosed that severe hypotony after cidofovir injections is associated with ciliary body atrophy. CONCLUSIONS: Intraocular pressure decreases after the initial 20-microgram cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus) after three injections. Effects on the ciliary body are the main cause of the decrease after cidofovir injections.

Low-dose intravitreal cidofovir (HPMPC) therapy of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.

PURPOSE: The authors have shown that long-term treatment of cytomegalovirus (CMV) retinitis with 20-microgram intravitreal injections of cidofovir (HPMPC) is highly effective but may be associated with iritis and profound hypotony. They evaluated the efficacy and safety of 10-microgram intravitreal injections of cidofovir and made comparisons with their findings of 20-microgram injections. METHODS: The current study was conducted as a nonrandomized consecutive case series at the AIDS Ocular Research Unit of the University of California at San Diego. Twenty-seven eyes of 18 patients were injected with 10 micrograms intravitreal cidofovir and had complete follow-up. These were compared with another consecutive series of 24 eyes of 17 patients injected with 20 micrograms of cidofovir. MAIN OUTCOME MEASURES: The main outcome in this study was the incidence of failure to respond to treatment with 10-microgram injections. The authors also compared the time to progression of CMV retinitis after the initial intravitreal injections of 10 micrograms and 20 micrograms of cidofovir. Secondary outcomes included incidence of iritis and changes in intraocular pressure (IOP) after cidofovir injections. RESULTS: The median time to retinitis progression was 45 days after a single intravitreal injection of 10 micrograms cidofovir compared with 55 days with the authors' series of 20-microgram injections. This difference was statistically significant (P = 0.033, log-rank test) and appeared to be due principally to a 26% incidence of primary failure in the 10-microgram group (progression > or = 750 microns within 28 days, P = 0.0017 Wilcoxon test). Progression after a second injection of 10 micrograms cidofovir was more rapid (32 days, P = 0.037). The incidence of iritis after 10-microgram injections was 2.2% compared with 23% with 20-microgram injections (P = 0.003, Fisher's exact test, two-tailed). There was less decrease in IOP between the baseline injection and subsequent visits in the 10-microgram group. CONCLUSIONS: Treatment of CMV retinitis with 10-microgram intravitreal cidofovir injection was not as effective as with 20 micrograms and may allow development of drug resistance, but there were fewer side effects with the 10-microgram dose. The drug appears to have a narrow therapeutic index, and other attempts at reducing the side effects while preserving the long-acting effect, such as liposome delivery, may be warranted.