Exudative retinopathy and detachment: a late reactivation of retinopathy of prematurity after intravitreal bevacizumab.

A 25-week postmenstrual age premature infant was treated with bilateral intravitreal bevacizumab for retinopathy of prematurity at 35 weeks' PMA. Postinjection, the retinal vessels progressed anteriorly within the retina. The patient presented 1 year after injection with bilateral exudative retinal detachments. The right eye was treated with intravitreal bevacizumab, laser ablation, and scleral buckling, resulting in resolution of the exudation and detachment. The left eye was treated with vitrectomy and lensectomy, but persistent exudation and detachment remained. This case demonstrates the rare complication of exudative retinal detachment in the setting of retinopathy of prematurity, which may become more common with increasing use of bevacizumab. Importantly, it also demonstrates the need not only for frequent examination after bevacizumab injection for retinopathy of prematurity but long-term follow-up as well, until either the retina is fully vascularized or peripheral ablation is performed.

Reactivation of retinopathy of prematurity after bevacizumab injection.

OBJECTIVE: To report late reactivation and progression of retinopathy of prematurity (ROP) after intravitreal bevacizumab monotherapy. METHODS: Retrospective review of 9 patients (17 eyes) with recurrence of ROP after initial treatment with intravitreal bevacizumab monotherapy. Data collected included (1) location and stage of ROP activity, (2) number and timing of treatments, and (3) structural outcomes. RESULTS: Mean age at treatment-requiring recurrence was 49.3 weeks (SD, 9.1 weeks; minimum, 37 weeks; maximum, 69 weeks) postmenstrual age (PMA). The mean time between initial treatment and treatment-requiring recurrence was 14.4 weeks, with a minimum of 4 and maximum of 35 weeks. Fives eyes progressed to retinal detachment (4 eyes stage 5, 1 eye stage 4a). Age at retinal detachment ranged from 49 to 69 weeks PMA with a median of 55 weeks PMA and mean of 58.4 weeks PMA. No eye that received laser treatment for recurrence progressed to retinal detachment. CONCLUSIONS: Although intravitreal bevacizumab treatment is effective in inducing regression of ROP, the effect may be transient. Recurrence can occur later in the course than with conventional laser therapy. Late retinal detachment can occur despite early regression. Longterm favorable structural outcome may require extended observation and retreatment. Laser may be a useful treatment for recurrences.

Topical ophthalmic moxifloxacin elicits minimal or no selection of fluoroquinolone resistance among bacteria isolated from the skin, nose, and throat.

PURPOSE: To investigate whether moxifloxacin therapy of bacterial conjunctivitis in children changes the moxifloxacin susceptibility of bacterial isolates in eyes, cheeks below eyes, nares, and throat. METHODS: Patients (age: 1 to 12 years, n = 105) with bacterial conjunctivitis were treated topically with moxifloxacin three times a day for 7 days. Gender- and age-matched subjects with normal eyes (age: 1 to 12 years, n = 57) served as the control group. Microbiological specimens were collected on days 1 (prior to therapy), 8 (1 day after end of therapy), and 42 (follow-up). Specimens were processed to recover total bacteria and bacteria that grew on fluoroquinolone-selective media. Bacteria were identified to the species level and susceptibility to moxifloxacin and selected other antibiotics determined. RESULTS: The primary pathogens recovered from the infected eyes on day 1 before therapy were Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. None of the pre-therapy isolates of H. influenzae and S. pneumoniae were resistant to moxifloxacin. Isolates of these two pathogenic species were also recovered primarily from the nose and eyes. Moxifloxacin-resistant S. aureus isolates (minimum inhibitory concentration 1.0 µg/mL or greater) were recovered from the nose and throat prior to topical dosing on day 1. However, there was no change in the frequency of moxifloxacin-resistant isolates of S. aureus following treatment with moxifloxacin. CONCLUSION: Treatment of conjunctivitis with topical ophthalmic moxifloxacin did not select for moxifloxacin resistance in H. influenzae, S. pneumoniae, or S. aureus in the eye or distal body sites.

Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin.

PURPOSE: To compare the kinetics and speed of kill of Streptococcus pneumoniae and Haemophilus influenzae on exposure to three topical ophthalmic antibiotic solutions. MATERIALS AND METHODS: Bacterial conjunctivitis isolates of S. pneumoniae and H. influenzae were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and water (control). At 15, 30, 60, 120, and 180 minutes after exposure, aliquots were collected, cells were cultured, and viable cell counts were determined using standard microbiological methods. RESULTS: Moxifloxacin achieved 99.9% kill (3-log reduction) at approximately 2 hours for S. pneumoniae and at 15 minutes for H. influenzae. Tobramycin and gentamicin did not achieve 3-log reduction of S. pneumoniae during the 180-minute study period. An increase in bacterial growth was noted for these isolates. Gentamicin took more than 120 minutes to achieve the 3-log reduction of H. influenzae and tobramycin did not reach the 3-log reduction of this pathogen during the 180-minute study period. CONCLUSION: Moxifloxacin killed S. pneumoniae and H. influenzae in vitro faster than tobramycin and gentamicin, suggesting its potential clinical benefit as a first-line treatment for bacterial conjunctivitis to minimize patient symptoms and to limit the contagiousness of the disease.

Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.

It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis. A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae. In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.

Safety and tolerability of olopatadine 0.2% in children and adolescents.

OBJECTIVE: The aim of this study was to evaluate the safety of olopatadine hydrochloride ophthalmic solution 0.2% in children and adolescents 3-17 years of age. METHODS: In this 6-week, randomized, double-masked safety evaluation, eligible subjects with asymptomatic eyes underwent in-office visits at weeks 1, 3, and 6 and were contacted by telephone at weeks 2, 4, and 5. Qualified subjects were assigned randomly in a 2:1 ratio of olopatadine 0.2% to vehicle (identical formation without the active ingredient) for dosing on a once-daily schedule. Safety parameters assessed included adverse events, visual acuity, ocular signs (slit-lamp assessments), dilated fundus examinations, intraocular pressure (IOP), pulse, and blood pressure. RESULTS AND DISCUSSION: An evaluation of 126 subjects (age range, 3-17) revealed no clinically relevant treatment-related changes in visual acuity, IOP, slit-lamp assessments, fundus examinations, or cardiovascular parameters. All adverse events reported were mild or moderate. CONCLUSIONS: Olopatadine 0.2% administered once-daily for 6 weeks is safe and well tolerated in children and adolescent patients.

Perception and quality of life associated with the use of olopatadine 0.2% (Pataday) in patients with active allergic conjunctivitis.

This 28-d, open-label, multicenter, single-arm clinical study was designed to evaluate perceptions of olopatadine 0.2% in patients with active ocular allergic signs and symptoms. The study enrolled 330 patients, 5 to 94 y of age, who had previously used olopatadine 0.1% for active allergic conjunctivitis. Most patients were white (n=230; 70.1%) and female (n=239; 72.9%). Of all enrolled patients, 328 were evaluable for analysis. Throughout the study, patients instilled 1 drop of olopatadine 0.2% into each eye once daily; adverse events were documented and ocular evaluations were conducted to ensure patient safety. Direct evaluations of efficacy were not performed. On days 1 and 7, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire, recorded their perceptions of olopatadine 0.1% (day 1) or 0.2% (day 7), and had their ocular allergies assessed globally. On each of the first 6 d of treatment, patients also completed a telephone-based perception questionnaire. On day 28, patients returned to the study center, reported their treatment perceptions, had their ocular allergies assessed, and exited the trial. Overall, patients had a positive perception of olopatadine 0.2%. Patients were more satisfied with olopatadine 0.2% than they remembered being with olopatadine 0.1% (289 vs 257 patients; 87.6% vs 77.8%; P<.05). The majority of the 48 patients who wore contact lenses (n=42; 88%) believed that they could wear their contacts as desired. Significant improvement was noted in all categories of the Rhinoconjunctivitis Quality of Life Questionnaire (P<.0001). No unexpected safety findings were reported. Patients perceived olopatadine 0.2% to be effective and well tolerated.

An assessment of the tolerability of moxifloxacin 0.5% compared to azithromycin 1.0% in DuraSite.

This subject-masked, randomized, active and placebo-controlled study compared subjects' perceptions of two antibiotic ophthalmic drops. One hundred and twenty-five healthy volunteers received two of the following solutions: moxifloxacin 0.5% ophthalmic solution (Vigamox((R)), Alcon Laboratories, Inc., Ft Worth, TX, USA), azithromycin 1% in DuraSite((R)) (AzaSite(), Inspire Pharmaceuticals, Inc., Durham, NC, USA), or Tears Naturale II((R)) (Alcon Laboratories, Inc., Ft. Worth, TX, USA) in contralateral eyes. Immediately following instillation and at 1, 3, 5, and 10 minutes thereafter, subjects rated comfort, acceptability, and blurring on 0-10 point analog scales stating their preference of treatment. Among subjects receiving moxifloxacin and azithromycin in contralateral eyes, 84% preferred moxifloxacin. Moxifloxacin was rated more comfortable and acceptable with less blurring than azithromycin (p < 0.0001). These differences were observed in both the adult and pediatric populations. Ocular adverse events (redness, irritation, stinging, burning, dryness, itching and chemosis) were observed in 18 (17.3%) eyes receiving azithromycin and 1 (1%) eye receiving moxifloxacin. Moxifloxacin was significantly more tolerable than azithromycin in healthy adult and pediatric eyes. Tolerability and patient acceptance affect compliance; thus these data should be of significance to the clinician.

Controlling contagious bacterial conjunctivitis.

BACKGROUND: Recent outbreaks (epidemics) of Streptococcus pneumoniae conjunctivitis, involving hundreds of patients, underscore the importance of following recommended guidelines to minimize disease transmission. These include the use of antimicrobial agents capable of minimizing patients' symptoms and the duration of the infectious period when disease can be transmitted to others. PURPOSE: To compare the amount of time required forvarious antibiotic solutions to kill S. pneumoniae, a common cause of bacterial conjunctivitis. MATERIALS AND METHODS: Isolates of S. pneumoniae from three patients were exposed to selected ophthalmic antibiotic products: moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and polymyxin B 10,000 IU-trimethoprim 1.0%. The products were diluted 1:100 and 1:1000 for testing. At 15, 30, 60, 120, and 180 minutes after exposure, aliquots of broth were withdrawn, the cells were separated and cultured, and the viable cell count was determined. RESULTS: Moxifloxacin killed actively growing S. pneumoniae faster and to a greater extent than did the other three antibiotic products when tested at concentrations corresponding to tear film concentrations 5 to 10 minutes and 30 to 60 minutes after instillation of the products. CONCLUSIONS: Moxifloxacin killed S. pneumoniae in vitro faster than did the other antibiotics. Consequently, its use should complement other generally accepted measures for minimizing patients' symptoms and limiting the contagiousness of bacterial conjunctivitis. Also, this is consistent with the recommendations of other investigators to prescribe the most recent generation of fluoroquinolone antibiotics for the specific purpose of limiting the spread of bacterial resistance.

Pharmacology, clinical efficacy and safety of olopatadine hydrochloride.

Olopatadine is a multimechanism anti-allergic agent that inhibits H(1) receptor activation and stabilizes mast cell membranes, blocking the release of allergic and inflammatory mediators. Studies in human conjunctival mast cells clearly demonstrate, in the relevant tissue and species, olopatadine's inhibition of histamine release, which was subsequently confirmed in allergen-challenged subjects. Its comfort and tolerability may be related to the absence of perturbation of cell membranes, in contrast to many anti-allergics, whose disruption of membranes lead to histamine release even at therapeutically relevant concentrations. In preclinical and clinical studies, olopatadine had greater efficacy and comfort than other anti-allergic agents available today for ophthalmic use.

Efficacy and safety of 0.5% levofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis in pediatric patients.

PURPOSE: To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (Quixin; Santen, Napa, CA) with 0.3% ofloxacin (Ocuflox; Allergan Inc., Irvine, CA) and placebo for the treatment of pediatric bacterial conjunctivitis. METHODS: This study was a subset analysis of 167 pediatric patients (age range, 1 to 16 years) from two randomized, double-masked, multicenter, parallel group studies. Eye drops were instilled every 2 hours on days 1 and 2 and every 4 hours on days 3 through 5. Ocular signs and symptoms were noted, and conjunctival cultures were obtained on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). Endpoint was defined as the last evaluable observation. Microbial and clinical outcomes were based on culture results and cardinal signs, respectively. RESULTS: At endpoint (mean of 6.5 days for 118 evaluable patients), 0.5% levofloxacin treatment demonstrated greater microbial eradication rates (percentage of patients with absence of causative organisms cultured at baseline) compared with 0.3% ofloxacin or placebo. In children age 2 to 11 years, this finding was statistically significant in favor of 0.5% levofloxacin (87% vs 62% with 0.3% ofloxacin [P < or =.032] and 88% vs 24% with placebo [P <.001]). No significant differences between treatment groups in microbial eradication rates were noted in other age subgroups. CONCLUSIONS: After 5 days of therapy, 0.5% levofloxacin ophthalmic solution was found to be safe and effective in treating pediatric bacterial conjunctivitis. Treatment with 0.5% levofloxacin achieved microbial eradication rates in children that were statistically superior to those attained with 0.3% ofloxacin or placebo.

A phase III clinical trial of 0.5% levofloxacin ophthalmic solution versus 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis.

OBJECTIVE: To compare the efficacy and safety of 0.5% levofloxacin ophthalmic solution (QUIXIN) with 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis. DESIGN: Prospective, randomized, active-controlled, double-masked, multicenter study. PARTICIPANTS: Four hundred twenty-three patients with a clinical diagnosis of bacterial conjunctivitis were enrolled. METHODS: Patients were randomly assigned to receive either 0.5% levofloxacin (n = 211) or 0.3% ofloxacin (n = 212) for 5 days (every 2 hours on days 1 and 2 and every 4 hours on days 3-5). Conjunctival cultures were obtained, and ocular signs and symptoms were evaluated on day 1 (baseline), days 3 to 5 (interim), and days 6 to 10 (final). End point was defined as the last evaluable observation. MAIN OUTCOME MEASURES: Primary microbial and clinical outcomes were based on culture results and resolution of cardinal signs, respectively. Secondary efficacy assessments included evaluations of ocular signs and symptoms. RESULTS: Two hundred eight patients (levofloxacin, n = 109; ofloxacin, n = 99) were evaluated for efficacy. Microbial eradication rates were significantly greater in the 0.5% levofloxacin treatment group compared with the 0.3% ofloxacin group at both the final visit (89% vs. 80%, P = 0.034) and at end point (90% vs. 81%; P = 0.038). Treatment with 0.5% levofloxacin was significantly more effective in resolving photophobia than was 0.3% ofloxacin treatment (94% vs. 73%, P = 0.006). Both study medications were well tolerated, with a low incidence of adverse events. CONCLUSIONS: Although clinical cure rates in the 0.5% levofloxacin and 0.3% ofloxacin treatment groups were similar, a 5-day treatment regimen with 0.5% levofloxacin achieved microbial eradication rates that were statistically superior to those attained with 0.3% ofloxacin. Despite the higher concentration of active drug in 0.5% levofloxacin versus 0.3% ofloxacin, there was no difference between treatment groups in the incidence of treatment-related adverse events.