Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis. Analysis and prevention.

BACKGROUND AND OBJECTIVE: The authors characterize and analyze the incidence of a previously reported mild anterior nongranulomatous uveitis associated with intravitreal injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), also termed cidofovir (Vistide, Gilead Sciences, Foster City, CA). This is an acyclic nucleoside phosphonate analogue with a potent anticytomegalovirus effect. The authors also analyzed the effects of probenecid therapy, as well as prophylaxis with probenecid plus topical corticosteroids and cycloplegics on the course and outcome of the uveitis. METHODS: Prospective case series from a tertiary referral center, which included 46 consecutive patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. There was a total of 130 injections in 69 eyes treated with 20 micrograms of intravitreal HPMPC. Forty-one patients (119 injections) received oral probenecid, 5 patients (11 injections) did not, and 21 patients (53 injections) received topical corticosteroids and cycloplegics as an adjuvant to probenecid in the prophylaxis of iritis. RESULTS: Mild to moderate nongranulomatous iritis was seen in 26% of patients after their first injection (n = 12). Patients receiving probenecid prophylaxis after first injection had a significantly lower frequency of iritis versus patients who did not receive probenecid at the time of first injection (P = 0.0089). In contrast, treatment with topical corticosteroid and cycloplegics after injection did not statistically significantly affect the frequency of iritis in patients (P = 0.44). The development of iritis after a second injection of HPMPC was more likely if it had occurred after the initial injection (P = 0.015; Fisher's exact test). All cases of iritis were treated with topical corticosteroids and cycloplegics, and there was no permanent impairment of vision secondary to iritis after HPMPC injection in any eyes. CONCLUSIONS: Anterior uveitis was seen in 26% of patients after first-time HPMPC injection. Concomitant use of probenecid appears to decrease the frequency of the iritis from 71% to 18% in patients with AIDS and CMV retinitis after the first intravitreal injection of HPMPC. Topical corticosteroid administration after injection (before iritis) was ineffective in preventing iritis treatment with topical corticosteroids and cycloplegics resulted in resolution of all iritis cases.

A histopathological, ultrastructural and immunohistochemical study of congenital hereditary retinoschisis.

OBJECTIVE: To confirm our earlier histopathological and electron microscopic findings in congenital hereditary retinoschisis (CHRS) in two additional globes and to further evaluate the nature and origin of the intraretinal filaments by means of immunohistochemical analysis. PATIENTS: Three white men with CHRS, aged 83 years (patient I) (two globes), 55 years (patient 2) (two globes) and 33 years (patient 3, nephew of patient 2) (one globe). OUTCOME MEASURES: Findings on histopathological study and electron microscopy (patient I) and immunohistochemical analysis (all five globes). RESULTS: Histopathological examination showed extensive extracellular deposition of amorphous material positive for periodic acid-Schiff reagent in the outer schisis layer and focally in the macula. Ultrastructurally, the amorphous material represented filaments measuring 8 to 12 nm in diameter within degenerated Müller cells, with accumulation of these filaments in adjacent extracellular spaces. Similar, less severe changes were seen in the superonasal retina. Immunohistochemical studies showed focal reactivity for glial fibrillary acidic protein (GFAP) in the retina adjacent to the schisis cavity in all five globes, focal reactivity for S-100 protein in four retinas, rare focal staining for vimentin and neurofilaments in two retinas each and no reactivity for type I keratin or actin. CONCLUSIONS: The present study corroborates our previous work and provides pathological evidence that the retinal disorder extends beyond the limits of the schisis. The results of the immunohistochemical analysis are consistent with a glial cell origin of the filaments. We postulate that defective Müller cells produce GFAP and possibly S-100 protein, which accumulate within the retina and secondarily result in degeneration of these cells and schisis formation.

Rhegmatogenous retinal detachments in HIV-positive patients with ocular syphilis.

The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients. Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months. Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin. Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis. All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation. The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important. Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

Correlation between intraocular pressure and CD4+ T-lymphocyte counts in patients with human immunodeficiency virus with and without cytomegalovirus retinitis.

PURPOSE: To determine the intraocular pressure in patients with human immunodeficiency virus (HIV) with and without cytomegalovirus retinitis, and to correlate intraocular pressure with CD4+ T-lymphocyte count and the presence, extent, and activity of cytomegalovirus retinitis. METHODS: Intraocular pressure was measured with calibrated Goldmann applanation tonometers in two groups of patients. Group A included 84 patients with HIV (120 eyes) with cytomegalovirus retinitis, and Group B included 110 patients with HIV (183 eyes) without cytomegalovirus retinitis. Thirty-three patients without HIV (66 eyes) were included as a control group. Step-wise regression analysis of intraocular pressure included correlation with cytomegalovirus retinitis (presence, extent, and activity), CD4+ T-lymphocyte count, age, and gender. RESULTS: The mean intraocular pressure was 9.8 mm Hg in Group A, 12.6 mm Hg in Group B, and 16.1 mm Hg in the control group. All three groups were statistically different from each other when intraocular pressure was compared (P < .0001). Step-wise regression showed that low CD4+ T-lymphocyte count (r2 = .20; P < .0001) and extent of cytomegalovirus retinitis (r2 = .08; P = .007) both correlated to low intraocular pressure. CONCLUSION: Intraocular pressure is lower than normal in patients with HIV. Decreased CD4+ T-lymphocyte count is the major association with low intraocular pressure (20% of the effect); extent of cytomegalovirus retinitis accounts for 8% of the effect. Knowledge of the normal range of intraocular pressure in patients with HIV will be important to the understanding and treatment of glaucoma and other disorders or treatments affecting intraocular pressure.

Silicone oil's properties make it a versatile tool for vit/ret surgery.

Silicone oil initially was perceived as a surgical tool to separate proliferative tissue from the retinal surface. The role of silicone oil as an intraocular tamponade became more clearly established following the introduction of trans pars plana vitrectomy in 1970 and the significant subsequent refinements in surgical techniques and technology. Silicone oil maintains an important place in the vitreoretinal surgical armamentarium. It may help preserve sight in some otherwise inoperable eyes. Future research may utilize silicone oil as a reservoir for the slow release of a therapeutic concentration of lipophilic drugs that inhibit viral retinitis or the proliferation of epiretinal membranes.

Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis.

This study evaluated intravitreous and plasma ganciclovir and foscarnet concentrations after intravenous administration in AIDS patients with cytomegalovirus (CMV) retinitis and retinal detachment. Undiluted vitreous samples were prospectively obtained from 60 eyes (52 patients) at the time of pars plana vitrectomy. Thirty-three plasma samples (from 27 patients in the initial group of 52) were obtained simultaneously during surgery on 33 eyes. High-pressure liquid chromatography showed the mean vitreous ganciclovir concentrations in patients on induction and maintenance therapy were, respectively, 4.74 +/- 1.49 microM (n = 24) and 3.29 +/- 1.84 microM (n = 30; P = .005). Simultaneous plasma ganciclovir concentrations were less than the vitreous concentrations in 78% of the patients. The mean intravitreous foscarnet concentrations in patients receiving induction dosages were 189 +/- 177 microM (n = 5) versus 163 +/- 167 microM (n = 4; P > .20) for those receiving maintenance therapy. The foscarnet vitreous plasma concentration ratio averaged 1.43. Current drugs and doses for CMV retinitis result in borderline or progressively subtherapeutic concentrations.

Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.

PURPOSE: The authors previously conducted a pilot, dose-escalating study which suggested that a 20-micrograms dose of intravitreal cidofovir (HPMPC) may be safe and effective in treating cytomegalovirus (CMV) retinitis in humans. The purpose of this series is to expand the authors' prior experience with the 20-micrograms dose of cidofovir as the sole treatment for CMV retinitis in patients with acquired immune deficiency syndrome. METHODS: The study design was an unmasked consecutive case series trial in a single-center institutional retina referral practice. Eligible patients with acquired immune deficiency syndrome had active CMV retinitis in at least one eye and no evidence of extraocular CMV disease. Patients received a 20-micrograms cidofovir trans pars plana injection and were treated with concomitant oral probenecid. Retreatments were performed for progression of retinitis as determined by serial fundus photographs judged independently by three observers. The primary outcome was time to retinitis progression determined by Kaplan-Meier analysis. Both globes of one patient who had unilateral retinitis were examined pathologically. RESULTS: There were 37 cidofovir injections in 24 eyes of 17 patients. The median time to retinitis progression after the initial 24 injections was 55 days. The median time to retinitis progression after 8 repeat cidofovir injections was 63 days. There was a significant decrease in intraocular pressure from baseline to both 2 and 4 weeks after injection. A mild to moderate iritis developed in five (20.8%) eyes that responded well to topical medications. Results of histopathologic examination of one treated globe did not show any significant toxic effects. CONCLUSIONS: This study demonstrates that prolonged arrest of the progression of CMV retinitis may be obtained with a single 20-micrograms cidofovir intravitreal injection. In addition, the effect of the drug appears to be maintained after a second injection. The effects of cidofovir in causing uveitis and a slight lowering of the intraocular pressure require further study.

Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: In this study we evaluated the safety and efficacy of the nucleoside phosphonate analogue intravitreal cidofovir to treat cytomegalovirus retinitis in humans. METHODS: We conducted a phase I/II unmasked consecutive case series in a single-center institutional referral practice. Eligible patients with the acquired immunodeficiency syndrome had active cytomegalovirus retinitis in at least one eye, despite adequate intravenous therapy with ganciclovir or foscarnet, were intolerant to intravenous therapy, were noncompliant with intravenous therapy, or refused intravenous therapy. In a preliminary safety study (Group 1), ten eyes of nine patients received 14 injections of cidofovir while being treated concurrently with intravenous ganciclovir. In a dose-escalating efficacy study (Group 2), eight eyes of seven patients received 11 injections of cidofovir as sole treatment for cytomegalovirus retinitis. The primary outcome was time to retinitis progression. RESULTS: In the Group 1 eyes receiving 20 micrograms of cidofovir, the median time to retinitis progression was between 49 and 92 days (mean, 78 days). In Group 2 eyes treated with 20 micrograms cidofovir, the median time to retinitis progression was 64 days (mean, 63 days). Hypotony occurred in the two eyes treated with a 100-micrograms dose of cidofovir and in one of three eyes receiving a 40-micrograms dose. No adverse effects resulted from the remaining 20 cidofovir injections. CONCLUSIONS: Cidofovir (also known as HPMPC) appears to be safe and effective for the local treatment of cytomegalovirus retinitis, providing a long duration of antiviral effect. These preliminary results indicate that additional studies should be performed to investigate more fully this promising medication.

Perioperative ofloxacin vs. tobramycin: efficacy in external ocular adnexal sterilization and anterior chamber penetration.

OBJECTIVE: To compare the efficacy of two treatment regimens, tobramycin drops-erythromycin ointment and ofloxacin drops-placebo ointment, in sterilizing the external ocular adnexa when given perioperatively. A second objective was to determine the aqueous humour concentration of ofloxacin and tobramycin. DESIGN: Randomized double-blinded clinical trial. SETTING: University-affiliated hospital. PATIENTS: Patients aged 18 years or more scheduled to undergo planned cataract surgery who were judged likely to complete the trial. NUMBERS: Of 55 patients enrolled 6 were disqualified and 49 completed the trial. INTERVENTIONS: Preoperative instillation of 10 drops of a 0.3% solution of ofloxacin (26 eyes) or tobramycin (23 eyes) in the operative eye, starting the evening before surgery. Tobramycin-treated eyes received erythromycin ointment after surgery; ofloxacin-treated eyes received petrolatum ointment. Lid and conjunctival swabs were obtained from both eyes on the day before surgery (visit 1), at surgery (visit 2) and on the first postoperative day (visit 3). Aqueous humour samples were obtained from the study eyes at surgery. MAIN OUTCOME MEASURES: Threshold growth of bacteria on culture, aqueous humour concentration of ofloxacin or tobramycin. RESULTS: At visit 1, 96% of all eyes had positive cultures; this result persisted at visits 2 and 3 for the control eyes. For the treated eyes the incidence of positive cultures decreased from visit to visit. By visit 3 lid cultures were positive for 7 (27%) of the ofloxacin-treated eyes and 7 (30%) of the tobramycin-treated eyes; conjunctival cultures were positive for 0 (0%) of the ofloxacin-treated eyes and 1 (4%) of the tobramycin-treated eyes. No significant differences were seen in culture positivity between the treatment groups at any visit. The mean aqueous humour concentration of ofloxacin was significantly higher than that of tobramycin (0.4084 vs. 0.0279 microgram/mL) (p < 0.001). CONCLUSIONS: Both ofloxacin-placebo treatment and tobramycin-erythromycin treatment were more effective than no treatment in sterilizing the external ocular adnexa. The two treatments were equally efficacious in eliminating bacteria, more successfully in the conjunctiva than the lids. Topically administered ofloxacin demonstrated significantly greater anterior chamber penetration than topically administered tobramycin.

Fungal invasion of seven hydrophilic contact lenses.

In six patients we reviewed the clinical, microbiologic, and histopathologic findings of seven hydrophilic contact lenses that had been infiltrated by fungi. Three patients had visual blurring or irritation and redness while wearing a contaminated lens; of these, two were unaware of any lens deposits. Three of the lenses from two patients were spares kept in storage for six months and one year, respectively. One contaminated lens had been torn and was kept in a case while a loaner lens was worn. Culture of this lens grew Cladosporium species. The contact lens case from one patient grew Penicillium species. Gross pathologic inspection disclosed multiple brown deposits in five lenses, multiple gray infiltrates in one lens, and a white infiltrate in one lens. Light microscopic examination disclosed partial-thickness (three lenses) or full-thickness (four lenses) invasion of the lens matrix by fungi, which contained granular, brown pigment in six lenses.

Ocular anomalies in anencephaly: a clinicopathological study of 11 globes.

Eleven globes of seven anencephalic infants with a gestational age of 36 to 41 weeks were examined pathologically. Atrophy of the ganglion cell and nerve fibre layers of the retina was found in all cases; optic nerve atrophy was noted in all 10 specimens in which the optic nerve was identified. In addition to findings attributable to immaturity, including persistent pupillary membrane (in 10 globes) and incomplete formation of the anterior chamber angle (in 5), we noted retinal dysplasia (in 4), colobomata (in 2) and proliferative retinopathy (in 1). Uncommon or previously undescribed abnormalities in association with anencephaly included cystic malformations of the meninges, sclera and globe (in one case each).

Immunoblastic T-cell lymphoma presenting as an eyelid tumor.

A 59-year-old white man presented with an ulcerating mass of the left upper eyelid of 6 months' duration. A biopsy specimen of the tumor was diagnosed as an immunoblastic T-cell malignant lymphoma. The lesion completely regressed after 4000 cGy of cobalt-60 radiation therapy. In the ensuing 33 months, multiple, widespread skin nodules of the same neoplasm developed including a right upper eyelid tumor. To the authors' knowledge, this is the first reported case of an immunoblastic T-cell lymphoma initially manifesting as an eyelid neoplasm.