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Biomedical subjects

M B Raizman

Publications and source records attributed to M B Raizman.

At least 19 recordsLinked to original sources

A phase III, placebo controlled clinical trial of 0.5% levofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis.

AIM: To compare the efficacy and safety of levofloxacin 0.5% ophthalmic solution (Quixin) with placebo for treatment of bacterial conjunctivitis. METHODS: In this prospective, randomised, placebo controlled, double masked, multicentre study, 249 patients with bacterial conjunctivitis received either 0.5% levofloxacin (n = 126) or placebo (n = 123) for 5 days, administered every 2 hours on days 1-2, then every 4 hours on days 3-5. Cultures were obtained and signs/symptoms evaluated at baseline, interim, and final visits. The end point was the last evaluable observation. Primary microbial outcomes were based on culture results; clinical outcomes were based on resolution of cardinal signs. RESULTS: 117 patients (60 levofloxacin, 57 placebo) were evaluated. Microbial eradication rates were significantly greater with levofloxacin at all time points, reaching 90% at end point. In a subgroup analysis, differences in eradication rates at end point were most pronounced in children but were also statistically significant for levofloxacin in adults. Clinical cure rates were significantly greater with levofloxacin at final visit and end point. Statistically significant differences favouring levofloxacin were measured at end point for resolution of conjunctival discharge, bulbar conjunctival injection, palpebral conjunctival injection, burning/stinging, itching, and photophobia. Adverse events were similar between groups. Safety composite scores analysed by age indicated significantly fewer children on levofloxacin experienced worsening symptoms. CONCLUSIONS: Levofloxacin 0.5% ophthalmic solution is safe and effective for treatment of bacterial conjunctivitis.

Adolescent↗

Lens changes in hereditary hyperferritinemia-cataract syndrome.

PURPOSE: To provide detailed description and illustration of the lens changes found in hereditary hyperferritinemia-cataract syndrome, a newly reported autosomal dominant condition. METHODS: Observational case reports. A 19-year-old man was referred for evaluation of possible hereditary hyperferritinemia-cataract syndrome. His serum ferritin level was increased at 1291 microg/L during a routine screening examination. Genetic analysis revealed mutation G51C on chromosome 19, predicting an altered iron response element in L-ferritin mRNA. Subsequent evaluation of his 46-year-old father revealed similar findings. RESULTS: Multiple breadcrumb-like nuclear and cortical lens opacities were seen in this father-son pair. These cases represent the first detailed description and illustration of hereditary hyperferritinemia-cataract syndrome cataracts in the ophthalmic literature. CONCLUSION: Hereditary hyperferritinemia-cataract syndrome can be associated with distinct breadcrumb-like lens opacities. Recognition of these characteristic cataracts may aid identification and study of patients with this unusual disorder and provide insight into mechanisms of cataract formation.

Adult↗

Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B.

We have studied mechanisms controlling activation of the gelatinase B gene (matrix metalloproteinase-9) by fibroblast growth factor-2 (FGF-2) during angiogenesis, and the effects of the natural product curcuminoids on this process. Using a transgenic mouse (line 3445) harboring a gelatinase B promoter/lacZ fusion gene, we demonstrate FGF-2 stimulation of reporter gene expression in endothelial cells of invading neocapillaries in the corneal micropocket assay. Using cultured corneal cells, we show that FGF-2 stimulates DNA binding activity of transcription factor AP-1 but not NF-kappaB and that AP-1 stimulation is inhibited by curcuminoids. We further show that induction of gelatinase B transcriptional promoter activity in response to FGF-2 is dependent on AP-1 but not NF-kappaB response elements and that promoter activity is also inhibited by curcuminoids. In rabbit corneas, the angiogenic response induced by implantation of an FGF-2 pellet is inhibited by the co-implantation of a curcuminoid pellet, and this correlates with inhibition of endogenous gelatinase B expression induced by FGF-2. Angiostatic efficacy in the cornea is also observed when curcuminoids are provided to mice in the diet. Our findings provide evidence that curcuminoids target the FGF-2 angiogenic signaling pathway and inhibit expression of gelatinase B in the angiogenic process.

Angiogenesis Inhibitors↗

Effect of eye rubbing on signs and symptoms of allergic conjunctivitis in cat-sensitive individuals.

OBJECTIVE: To evaluate the effect of eye rubbing on signs and symptoms of allergic conjunctivitis in cat-sensitive individuals. DESIGN: Two prospective, nonrandomized comparative studies. PARTICIPANTS: Thirteen patients in the first study and 20 patients in the second study with a documented history of acute allergic conjunctivitis induced by exposure to cats were enrolled. INTERVENTION: In the first trial, all patients had one eye rubbed 15 times by the investigator without exposure to airborne allergens. Both eyes were evaluated after 5, 15, 30, and 60 minutes using subject questionnaires and slit-lamp examination. At least 1 week later, each patient was exposed to cat dander for 75 minutes; 15 minutes after entering the cat room, each patient had one eye rubbed 15 times by the examiner. Subjects' eyes were then evaluated using questionnaires and slit-lamp examination. In the second trial, the visits were identical to the first trial, except that the rubbed eye in each visit was rubbed 20 times and with more force, and that patients wore masks during exposure to cat dander. MAIN OUTCOME MEASURES: In both studies, the difference between patients' rubbed and nonrubbed eyes with respect to ocular itching, chemosis, and hyperemia was noted 5, 15, 30, and 60 minutes after controlled eye rubbing. RESULTS: Without exposure to the cat room, rubbed eyes exhibited increased itching at 5 minutes in both studies and at 15 minutes in the second study (P < 0.05), increased chemosis at 5 and 15 minutes in the second study (P < 0.05), and increased hyperemia at 5 minutes in the second study (P < 0.05) compared with nonrubbed eyes. During exposure to cat dander, rubbed eyes consistently exhibited increased itching at 5, 15, and 30 minutes in the first and second study as well as at 60 minutes in the second study compared with nonrubbed eyes. Furthermore, during exposure to cat dander, rubbed eyes consistently exhibited increased chemosis at 5 and 15 minutes (P < 0.05) and increased hyperemia at 5, 15, and 30 minutes (P < 0.05) in the second study compared with nonrubbed eyes. CONCLUSIONS: Firm eye rubbing causes a mild and transient increase in ocular itching, chemosis, and hyperemia. However, after exposure to cat allergens in cat-sensitive individuals, the effects of eye rubbing are longer and more dramatic. Eye rubbing may play a role in ocular signs and symptoms of allergic conjunctivitis in cat-sensitive individuals, especially after exposure to cat dander.

Acute Disease↗

Oral erythromycin treatment for childhood blepharokeratitis.

Blepharokeratitis is a chronic external ocular and adnexal inflammatory condition marked by erythematous and edematous lid margins, lid margin crusting and scaling, meibomian gland inflammation and inspissation, and conjunctival hyperemia. The associated keratitis usually involves the inferior cornea and is characterized by punctate epithelial keratopathy and marginal stromal infiltrates. The inflammation sometimes leads to corneal thinning, scarring, and vascularization. The standard therapy for adult blepharokeratitis includes lid hygiene, topical cortico-steroid preparations, and topical antibiotics. Oral tetracycline and its analogues, doxycycline and minocycline, are used in adults to treat associated meibomian gland dysfunction. Whereas blepharitis is common in children, blepharokeratitis is rare and is often associated with severe ocular and psychosocial morbidity. Treatment of youths may be problematic because of poor compliance with lid hygiene and therapy that includes drops and ointment.(1) Furthermore, the use of tetracycline and its analogues is contraindicated in children aged less than 8 years because it may cause dental enamel abnormalities. Isolated case reports have suggested that erythromycin may be a reasonable alternative to tetracycline in childhood blepharokeratitis.(2,3) We report on the successful treatment of this condition with oral erythromycin in 5 children.

Administration, Oral↗

Lepromatous uveitis diagnosed by iris biopsy.

Ocular leprosy is rarely seen in developed countries. We report the long-term follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin, iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy must be considered in the differential diagnosis of keratitis and uveitis.

Adult↗

A multicenter comparison of the ocular efficacy and safety of diclofenac 0.1% solution with that of ketorolac 0.5% solution in patients with acute seasonal allergic conjunctivitis.

Only one of several available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) is currently FDA approved for use in acute seasonal allergic conjunctivitis (SAC). Sixty patients with SAC and moderate itching and bulbar conjunctival injection were enrolled in a multicenter, randomized, double-masked, parallel-group trial comparing diclofenac sodium (DS) with ketorolac tromethamine (KT). Patients instilled 1 drop four times daily while awake for 14 days. Ocular signs and symptoms were evaluated at one and two weeks. The primary efficacy variables were itching and bulbar conjunctival injection. For both treatments, the ocular allergy sign and symptom scores were comparable at baseline. Both treatments evaluated in this study were well tolerated. Significant clinical and statistical reductions from baseline were observed in the primary efficacy variables. Treatment group differences were observed for the pain/soreness score with an advantage observed for the DS group at 30 minutes and at day 7. Our conclusion is that diclofenac sodium and ketorolac tromethamine acted similarly to reduce the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis. There was a statistically significant advantage for the DS group to be free of symptoms at the day 7 visit as compared to the KT group (20.7% vs. 3.2%).

Acute Disease↗

Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis.

PURPOSE: Two multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). METHODS: Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled. Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days. Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28. A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. RESULTS: When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest difference observed between treatments was 0.5 score unit, not clinically significant. There were no statistically significant differences in cell scores in either study (P > .05). No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). CONCLUSION: Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis.

Acute Disease↗

Pathogenesis of corneal infection: binding of Pseudomonas aeruginosa to specific phospholipids.

Clinical isolates of Pseudomonas aeruginosa were examined for binding interactions with phospholipids of corneal epithelium. Thin-layer chromatography (TLC) of lipids extracted from corneal epithelia followed by staining with an ammonium molybdate spray reagent revealed three phospholipid components, PL1, PL2, and PL3. The chromatographic mobility of PL1 was similar to that of the phospholipid standards phosphatidylinositol (PI) and phosphatidylserine (PS), which were not well resolved from one other; PL2 and PL3 comigrated with the standards phosphatidylcholine and phosphatidylethanolamine, respectively. By use of a TLC-bacterial overlay procedure, 35S-labeled P. aeruginosa organisms were shown to bind to PL1 but not to PL2 or PL3. P. aeruginosa binding to PL1 was concentration dependent. Alkaline methanolysis abolished the binding. PL1 was separated into two components, PL1-I and PL1-S, by chromatography on borate-treated TLC plates. Both PL1-I and PL1-S contained binding sites for P. aeruginosa. Mass spectral analysis identified PL1-I and PL1-S as PI and PS, respectively. Radiolabeled P. aeruginosa organisms were subsequently shown to bind to commercially available bovine PI and PS and synthetic dipalmitoyl-PS but not to other phospholipid standards, including bovine SM and PC or synthetic dioleoyl- and distearoyl-PC. A control Escherichia coli strain did not bind to either PS or PI. Tetramethylurea, a disrupter of hydrophobic associations, did not influence the binding of P. aeruginosa to PS or PI. P. aeruginosa bound to the monolayers of corneal epithelial cells. P. aeruginosa binding to the monolayer cultures as well as to rabbit corneas pretreated with exogenous PS and PI was significantly higher than that to those preincubated with PC or medium alone. The data suggest that phospholipids PS and PI present in mucus or on the cell surface may function as P. aeruginosa receptors and contribute to selective bacterium-host interactions responsible for initial colonization.

Animals↗

Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury.

Delayed re-epithelialization of the cornea after injury usually precedes stromal ulceration. Previous findings using a rat thermal injury model suggested that re-epithelialization is impeded by products of resident corneal cells, which destroy adhesive structures at the basement membrane zone. In this study, we provide additional evidence for this concept. Failure to re-epithelialize was found to correlate with an increase in the amounts of gelatinolytic matrix metalloproteinases present in the rat cornea. One of these gelatinases, gelatinase B, is synthesized by the resident corneal cells, and inhibitions of its synthesis correlated with inhibition of basement membrane dissolution. The matrix metalloproteinases collagenase and stromelysin are also synthesized by resident corneal cells in thermally injured corneas of rabbits, but the timing of bulk enzyme synthesis correlated more closely with deposition of repair tissue in the stroma than with failure to re-epithelialize. Nevertheless, in human corneas with repair defects, gelatinase B and collagenase are synthesized by cells in the basal layer of the epithelium directly adjacent to the basement membrane, suggesting that both could participate in dissolution of this structure. Importantly, treatment of thermally injured corneas with a synthetic inhibitor of matrix metalloproteinases significantly improved basement membrane integrity. These data support the concept that over-expression of matrix metalloproteinases by resident corneal cells impedes re-epithelialization after some types of corneal injury.

Animals↗

Choroidal and retinal detachment in antineutrophil cytoplasmic antibody-positive scleritis.

PURPOSE/METHODS: A 72-year-old woman with antineutrophil cytoplasmic antibody-positive vasculitis had a combined detachment of the choroid and retina. This unique initial manifestation was also associated with systemic and orbital manifestations, including brow ptosis, dacryoadenitis, and pneumonitis. RESULTS/CONCLUSIONS: This patient underwent vitrectomy for removal of a dense vitreitis and responded well to systemic cyclophosphamide. This case demonstrates that antineutrophil cytoplasmic antibody testing is useful for the diagnosis and treatment of Wegener's granulomatosis and microscopic polyarteritis-associated scleritis. The distinction between these two entities is often difficult to make.

Aged↗

Relapse of Mycobacterium leprae infection with ocular manifestations.

A case of ocular leprosy as the manifestation of persistent or relapsed Mycobacterium leprae infection approximately 20 years following treatment is reported. The clinical and pathological features of this case are described, and the molecular methods needed to arrive at the definitive diagnosis are examined. If blindness is to be averted, clinicians must have a high index of suspicion for the diagnosis of ocular leprosy when anterior segment changes are noted during ophthalmologic examination of a patient from an area in which M. leprae is endemic. The indolent nature of ocular leprosy may require lifelong surveillance and therapy to insure sight preservation.

Adult↗

Cell surface glycoproteins of corneal epithelium.

PURPOSE: To identify those plasma membrane glycoproteins of corneal epithelial cells that are synthesized in a higher amount or are downregulated during cell migration. METHODS: Primary cell cultures of rabbit corneal epithelium were used. Sialic acid and terminal galactose/N-acetylgalactosamine residues of plasma membrane glycoproteins of migrating and nonmigrating corneal epithelial cells were labeled using two well-characterized cell surface carbohydrate labeling techniques. The labeled glycoproteins were extracted in phosphate-buffered saline containing nonionic detergents and various protease inhibitors, and then they were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. RESULTS: At least 12 to 13 radiolabeled components (molecular weight, 240 kd to 21 kd) were detected in the fluorographs of both sialic acid and galactose-labeled cells. Regardless of the labeling technique used, one sialoglycoprotein (GP1, 240 kd) was found in a higher amount in the extracts of nonmigrating cells than in migrating cells, and another glycoprotein (GP12, 28 kd) was present in a higher amount in migrating than in nonmigrating cells. Furthermore, one sialoglycoprotein (GP13, 21 kd) was detected only in migrating cells, and two glycoproteins (GP10, 42 kd; GP11, 32 kd) with terminal galactose/N-acetylgalactosamine residues were present in a higher amount in migrating than in nonmigrating cells. CONCLUSIONS: This study has demonstrated that during corneal epithelial cell migration, the level of one membrane glycoprotein is markedly reduced, and the levels of four membrane glycoproteins are elevated. Further characterization of these glycoproteins should contribute to a better understanding of the mechanisms that modulate corneal epithelial sheet migration and wound healing.

Acetylgalactosamine↗

Treatment strategies for scleritis and uveitis associated with inflammatory bowel disease.

We treated 19 patients with anterior uveitis, episcleritis, or scleritis associated with inflammatory bowel disease. Adequate control of ocular inflammation was achieved in 16 patients (84%). Ocular inflammation was adequately controlled with corticosteroids alone, without systemic adverse effects, in only three patients, all of whom had anterior uveitis associated with ulcerative colitis. Systemic nonsteroidal anti-inflammatory drugs proved beneficial in six of seven patients, and one additional patient benefited from another anti-inflammatory drug (hydroxychloroquine sulfate). Systemic cytotoxic immunosuppressive therapy was used in the remaining seven patients, six of whom had bilateral disease. Ocular inflammation was controlled in six of these patients. Azathioprine was beneficial for scleritis but was less effective for anterior uveitis, especially in Crohn's disease, thus necessitating the use of another cytotoxic agent. HLA-B27-positive anterior uveitis was more refractory to corticosteroid therapy and was more likely to require systemic cytotoxic immunosuppressive therapy. With the medical and surgical strategies described, vision was improved or maintained in all patients in the study group.

Administration, Topical↗

One-year results of excimer laser photorefractive keratectomy for low to moderate myopia.

OBJECTIVE: Excimer photorefractive keratectomy is a promising method to reduce myopia. We evaluated the effectiveness, predictability, stability, and safety of photorefractive keratectomy performed by two surgeons at a single site with a 1-year follow-up. METHODS: An excimer laser (Summit Excimed UV200, Summit Technology, Waltham, Mass) was used to treat 47 eyes. Preoperative uncorrected visual acuity averaged 20/277 and ranged from 20/60 to 20/500. Spherical equivalent averaged -3.9 diopters and ranged from -1.5 to -6.1 D. RESULTS: One year postoperatively, best corrected visual acuity averaged 20/13 and ranged from 20/10 to 20/20. No patients lost any of best corrected visual acuity. The uncorrected visual acuity at 1 year averaged 20/20 and ranged from 20/10 to 20/200. Ninety-four percent of eyes had an uncorrected visual acuity of 20/40 or better; 83%, 20/25 or better; and 74%, 20/20 or better. An initial hyperopic overcorrection is followed by gradual regression to emmetropia during a 12-month period. Refractive spherical equivalent averaged 0.44 D and ranged from -3 to +2.6 D at 1 year. The proportion of eyes within 1 D of emmetropia was 80% at 1 year. The most significant shifts in refraction occurred between the first and second months, but small shifts occurred up to 12 months. Subgrouping the results according to age revealed a significantly greater effect with larger residual hyperopia in those older than 40 years. Patient satisfaction with the procedure was high. CONCLUSION: During a 1-year period, excimer photorefractive keratectomy appears to be an effective, predictable, stable, and safe method to reduce myopia. Age may play a role in the effectiveness of the procedure, with greater hyperopia resulting in those older than 40 years.

Adult↗