rifampin and Eye-Diseases

Certain polycyclic compounds with a coplanar ring structure (phenothiazines, thioxanthenes, 4-aminoquinolines, and amitriptyline), monocyclic sympathomimetic amines, and other drugs become concentrated in the eyes of animals following acute or chronic systemic administration. Some are known to cross the placental barrier and accumulate in the fetal eye. Following drug withdrawal, these substances disappear relatively slowly from ocular tissues compared with other tissues. The main reason for the accumulation of these compounds seem to be their affinity for the melanin of the uveal tract and pigment epithelium and they therefore do not accumulate in the eyes of albino animals. The mechanism of uptake by melanin probably involves a "charge transfer" reaction involving the transfer of an electron from drug to melanin, which acts as an "electron trap" and in consequence binds the donor compound firmly. The accumulation of a nontoxic drug in the eye is not necessarily of clinical significance, but ocular damage can occur in patients on long-term tricyclic agents when the amount, duration, and frequency of dosage are sufficiently high. The most serious form of ocular damage is pigmentary retinopathy, which, if caused by chloroquine, is irreversible. In contrast, phenothiazine retinopathy is reversible. Lesions may also be produced in anterior structures of the eye, usually the cornea and lens, by both chloroquine and the phenothiazines, but they are of a relatively minor nature. Possible mechanisms for the oculotoxicity of the phenothiazines and antimalarials are discussed, particularly in relation to melanin.

Topics: Amitriptyline; Animals; Chloroquine; Cornea; Eye; Eye Diseases; Female; Haplorhini; Humans; Lens, Crystalline; Phenothiazines; Pregnancy; Retinal Diseases; Rifampin; Structure-Activity Relationship; Thioxanthenes; Time Factors

Topics: Aged; Aminosalicylic Acids; Capreomycin; Chemical Phenomena; Chemistry; Color Perception; Drug Therapy, Combination; Ethambutol; Eye; Eye Diseases; Female; Humans; Isoniazid; Kidney Failure, Chronic; Male; Middle Aged; Rifampin; Tuberculosis, Pulmonary; Visual Acuity; Visual Fields

The aim of this study was to describe the ocular conditions in multibacillary (MB) leprosy patients treated with 2 year WHO multiple drug therapy (MDT), consisting of dapsone, clofazimine and rifampin, a regimen expected to reduce ocular complications of leprosy. We conducted comprehensive eye examinations in 202 Filipino MB leprosy patients before, during, and after WHO 2 year MDT. Assessments were carried out for at least 5 years. Inflammatory "lepra" reactions occurred in 62% (reversal reaction, 52%; erythema nodosum leprosum, 10%); most were mild. Eye abnormalities consisted mostly of diminished corneal sensitivity before MDT (6%) and lagopthalmos (n = 7, 3.4%). Six of 7 lagopthalmos cases occurred in a subset of 132 patients with facial patches (5%). Visual acuity scores, intra-ocular pressures and pupil cycle times were unremarkable. Bacillary invasion, keratitis, episcleritis, iridocyclitis, ectropion, synechiae, glaucoma and cataract formation were not detected. Scleral clofazimine pigmentation was frequent, resolving in most within 3 years of treatment cessation. Facial patches at presentation may denote a higher risk for lagopthalmos. We propose the generally low rates of ocular problems reflected mild lepra reactions, due to anti-inflammatory properties of clofazimine, a relatively young cohort, and a readily accessible community-based clinic permitting earlier diagnosis and prompt treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Clofazimine; Dapsone; Drug Therapy, Combination; Eye Diseases; Female; Humans; Infant; Leprostatic Agents; Leprosy, Multibacillary; Longitudinal Studies; Male; Middle Aged; Philippines; Prospective Studies; Rifampin; Young Adult

Ethambutol (EMB) is used as a fourth drug in paediatric anti-tuberculosis treatment. In current recommendations the dosage of EMB is calculated per kg body weight.. To present two studies investigating an appropriate EMB dosage in children, and observational data on its toxicity and efficacy.. EMB serum levels in children of different age groups were determined after single oral administration of EMB alone as well as after EMB combined with rifampicin, and optimal dosages were established. The efficacy and toxicity of these EMB dosages were examined retrospectively.. EMB serum levels were lower than those expected in adults receiving a similar oral dose, due to different pharmacokinetics and pharmacodynamics in childhood. Thereafter, children were treated with EMB doses calculated by body surface (867 mg/m2). Ocular toxicity occurred in 0.7% of cases and relapses in 0.8%.. Current recommended EMB dosages in childhood tuberculosis lead to subtherapeutic serum levels. It appears to be more valid to calculate the EMB dosage on the basis of body surface rather than body weight, leading to higher dosages especially in younger children. With these dosages, therapeutic serum levels are reached in all age groups, leading to a high efficacy of anti-tuberculosis treatment without increased ocular toxicity.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Antitubercular Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethambutol; Eye Diseases; Female; Humans; Male; Microbial Sensitivity Tests; Recurrence; Retrospective Studies; Rifampin; Tuberculosis

Topics: Adenoviridae; Administration, Oral; Animals; Bacteria; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Conjunctivitis; DNA-Directed RNA Polymerases; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Eye Diseases; Haemophilus Infections; Humans; Isoniazid; Mycobacterium; Mycobacterium tuberculosis; Rifampin; Tuberculosis; Vaccinia; Vaccinia virus

Topics: Aged; Animals; Aqueous Humor; Cataract; Clinical Trials as Topic; Conjunctivitis; Cornea; Dacryocystitis; Eye Diseases; Glaucoma; Humans; Iritis; Keratitis; Middle Aged; Rabbits; Retinal Detachment; Retinitis; Rifampin; Uveitis, Anterior; Vitreous Body

Government of India's Revised National TB Control Programme (RNTCP) has begun implementing daily fixed dose combination (FDC) anti-TB treatment regimen for drug sensitive TB patients in which ethambutol is given for six months. Prolonged ethambutol use is known to cause ocular adverse drug events (ADE).. To assess the magnitude of ocular ADEs in adult drug sensitive TB patients initiated on daily FDCs and to describe the demographic and clinical profile of patients with ocular ADEs.. We conducted a retrospective cohort study involving review of RNTCP records of all adult (age >14 years) drug sensitive TB patients initiated on daily FDCs between1. 714 patients were initiated on daily FDCs during the study period. It was unknown whether all patients had undergone assessment for ocular ADEs. However, of these 714 patients, 8 patients (1.1%) were documented to have had ocular ADEs. Seven of these 8 patients had received ethambutol more than 15 mg/kg body weight and had developed ocular symptoms (decreased/blurring of vision) 3 months after TB treatment initiation. Ethambutol was stopped in all these 8 patients. In 5 patients it was recorded that ocular ADEs had resolved following stoppage of ethambutol and in the remaining it was unknown.. The study confirms the occurrence of ocular ADEs among drug sensitive TB patients on daily FDCs and recommends strengthening of systems for assessing, documenting and managing ocular ADE.

Topics: Adult; Aged; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Combinations; Ethambutol; Eye Diseases; Female; Humans; India; Isoniazid; Male; Middle Aged; Pyrazinamide; Retrospective Studies; Rifampin; Tuberculosis; Vision Disorders

Topics: Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Bartonella henselae; Cat-Scratch Disease; Doxycycline; Drug Therapy, Combination; Eye Diseases; Eye Infections, Bacterial; Female; Fluorescein Angiography; Glucocorticoids; Humans; Immunoglobulin G; Optic Neuritis; Prednisone; Retinal Detachment; Retinitis; Rifampin; Tomography, Optical Coherence; Vision Disorders; Visual Acuity; Visual Fields; Vitrectomy; Vitreous Body

To report a case of anterior segment findings of presumed ocular tuberculosis using anterior-segment optical coherence tomography (AS-OCT; Visante, Carl Zeiss Meditec, Inc., Dublin, CA, USA).. A 78-year-old woman with persistent right ocular injection and pain of 2 weeks' duration was referred to our clinic. Unilateral stromal keratitis affecting the corneal periphery and angle granuloma with synechiae, scleritis, and anterior uveitis were noticed. Because of the patient's intensely positive tuberculin skin test, she was diagnosed with presumed intraocular tuberculosis. The anatomic structures of the anterior segment were monitored by AS-OCT before and after the treatment.. AS-OCT imaging showed a poorly demarcated amorphous lesion in the iridocorneal angle, corneal edema, narrowing and synechiae of the iridocorneal angle, and anterior chamber exudates and cells. Improvement of the corneal edema and a decrease of corneal thickness and exudates were observed after implementation of a daily regimen of antituberculous treatment. AS-OCT was useful for investigating the extent of the anterior synechiae and angle lesions.. AS-OCT allows noninvasive and noncontact analysis of the treatment response and is also useful to evaluate disease activity.

Topics: Aged; Anterior Eye Segment; Antitubercular Agents; Cataract Extraction; Corneal Edema; Drug Therapy, Combination; Eye Diseases; Female; Humans; Isoniazid; Pyrazinamide; Rifampin; Tomography, Optical Coherence; Treatment Outcome; Tuberculosis

(11R)-N,15-dideoxo-1-deoxy-1,15-epoxy-11-hydroxy-4-0methy l-8-0-(2, 2-dimethyl-1-oxopropyl)-3-[4-¿(2,4, 6-trimethylphenyl)methyl¿-1-piperazinyl]rifamycin has been evaluated as a potential hypolipidemic agent. As part of a safety evaluation program, a 3-month oral toxicity study was performed in which CGS 24565 was administered to beagle dogs via gelatin capsules at 10, 50, or 300 mg/kg/day. Ophthalmoscopic examinations (using focal illumination and indirect opthalmoscopy) on day 83 (week 12) revealed bilateral adnexal and corneal changes affecting 5 dogs (3 males, 2 females, 300 mg/kg/day). Ophthalmoscopically, dogs from the 300 mg/kg dose level exhibited the adnexal changes characterized as ptosis, conjunctivitis, episcleritis, and relaxed membrane nictitans, while the corneal changes were characterized as posterior stromal edema (cloudy, diffuse opacity usually accompanied by deep neovascularization; the diffuse edema masked the complete evaluation of other ocular structures) and stromal infiltrates in the area of Decement's membrane (appeared to be multifocal, polymorphic changes/alterations in Decement's membrane, or endothelial swelling). No changes from normal were seen clinically in the eyes of other dogs on this experiment. In those dogs affected by the ocular changes caused by CGS 24565, a visual deficit in acuity was suspected. The corneal changes, as manifested, were suggestive of permanent, irreversible corneal damage. Subsequent ophthalmoscopic examinations performed at established intervals during weeks 15 through 26, revealed abatement of the adnexal changes, while the corneal changes, as described above, remained generally unchanged, confirming irreversibility of the corneal changes within the recovery period of 13 weeks. Light microscopy confirmed irreversible corneal neovascularization, vacuolar degeneration of the keratocytes at 300 mg/kg, and polymorphic infiltrates in the region of Decement's membrane. The results demonstrate that the cornea was the target tissue of toxicity for CGS 24565, and indicated that the findings represent a significant toxic effect. The correlation of histopathological findings support the hypothesis of the diagnosis of interstitial stromal degeneration/atrophy. The potential for a similar result to the cornea of humans does exist. Due to these changes and other toxic effects associated with this class of compound, further development was terminated.

Topics: Administration, Oral; Animals; Anticholesteremic Agents; Cornea; Corneal Neovascularization; Corneal Opacity; Corneal Stroma; Dogs; Eye Diseases; Female; Male; Ophthalmoscopy; Rifampin; Sex Characteristics; Time Factors

Topics: Bacterial Vaccines; Clofazimine; Dapsone; Drug Therapy, Combination; Eye Diseases; Humans; Leprosy; Mycobacterium leprae; Rifampin

Topics: Ambulatory Care; Antitubercular Agents; Drug Interactions; Ethambutol; Eye Diseases; Female; Follow-Up Studies; Hospitalization; Humans; Kidney Failure, Chronic; Pregnancy; Pregnancy Complications, Infectious; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

Topics: Eye Diseases; Humans; Rifampin

Topics: Adult; Aged; Chorioretinitis; Choroiditis; Eye Diseases; Female; Humans; Male; Middle Aged; Optic Neuritis; Retinitis; Rifampin; Tuberculosis, Ocular; Uveitis; Uveitis, Anterior