A precise method of using rose bengal in the evaluation of dry eye and the detection of changes in its severity.
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Biomedical subjects
Publications and source records attributed to M B Abelson.
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The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of ophthalmic inflammatory disease. Currently four topical preparations are available: flurbiprofen and suprofen for the prevention of miosis during surgery; diclofenac for postoperative inflammation following cataract extraction, and ketorolac for the treatment of itching associated with seasonal allergic conjunctivitis. Caution should be exercised, however, as topical and systemic adverse effects may occur including stinging, photophobia, gastric sensitivity, and increased bleeding time. The mechanism of action of NSAIDs is discussed, complications associated with use, and the current and future roles of therapy.
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We conducted a historical cohort study of 1,954 myopic cosmetic contact lens wearers (1,258 disposable soft daily wear lens users and 696 conventional [nondisposable] soft daily wear lens users). Our aim was to estimate the rates of complications and symptoms among patients using daily wear disposable contact lenses on a regular disposal regimen and to compare these with rates for conventional soft daily wear users. Patients were selected from five contact lens practices in Denmark. Data were abstracted from the eye care practitioners' office records for the period October 1987 through December 1989. Virtually all of the disposable lens users were on a two-week disposal regimen. Overall, the prevalence of complications was significantly lower among the daily wear disposable lens users than among the conventional soft daily wear lens users. The incidence of corneal ulcers did not differ significantly between the two study groups. As compared to conventional soft daily wear lens users, disposable daily wear lens users reported symptoms less frequently at routine scheduled visits and had a lower rate of unscheduled visits for complications and symptoms.
Scanning electron microscopy was used to evaluate the corneal epithelium of rabbit eyes after administration of two preservative-free ocular lubricants, preservative-free artificial tear-1 (Hypotears PF) and preservative-free artificial tear-2 (Refresh), and 0.02% benzalkonium chloride. Animals were randomly assigned to either mild or exaggerated use regimens. A quantitative rating system was used to assess epithelial damage. With mild use, scanning electron microscopy revealed normal epithelial morphologic characteristics for both preservative-free artificial tear solutions (mean relative damage score, solution 1, 0.75 +/- 0.16; solution 2, 1.02 +/- 0.23), which were not significantly different from eyes treated with phosphate-buffered saline (1.38 +/- 0.38) or a mild dosage regimen of 0.02% benzalkonium chloride (1.20 +/- 0.12). Exaggerated use with preservative-free artificial tear solutions (solution 1, 1.31 +/- 0.21; solution 2, 1.35 +/- 0.08) induced minimal damage that was not different from control eyes treated with phosphate-buffered saline (1.26 +/- 0.13). Compared with an exaggerated use of 0.02% benzalkonium chloride (4.0 +/- 0.16), both preservative-free artificial tear solutions induced significantly less epithelial damage (P = .0001). These results suggest that with frequent-dosage regimens, preservation-free artificial tear solutions-1 and -2 are free of the toxic effects associated with preserved solutions.
The cyclooxygenase and lipoxygenase enzyme systems can metabolize a number of C20 polyunsaturated fatty acids. Although arachidonic acid is the usual substrate for these pathways, the eicosanoid precursor pool can be nutritionally manipulated by supplementation with alternative precursors, often generating less active or down-regulatory metabolic products. Prefeeding with gamma-linolenic acid, eicosapentaenoic acid, or a combination of both failed to influence the lagphase, epithelial migration rate, or epithelial wound healing kinetics after either 1N or 4N NaOH alkali burning of the rabbit cornea. Initial epithelial wound healing probably does not involve eicosanoid-mediated processes. Essentially linear epithelial healing kinetics continued to closure without a late decrease in wound edge velocity.
The objective of this study was to determine the therapeutic value of a wide variety of H1 antihistamines for potential ophthalmic use by performing ocular toxicity and efficacy tests in rabbits and humans. Fourteen antihistamines were formulated into ophthalmic preparations and were screened in the rabbit model; of these, thirteen were preliminary evaluated for toxicity and efficacy in humans. Based on comfort and efficacy, four (pheniramine, chlorpheniramine, dexbrompheniramine and pyrilamine) were selected for more extensive dose response and efficacy testing. 0.3% chlorpheniramine, dexbrompheniramine, pyrilamine and pheniramine significantly reduced histamine-induced itching (p less than or equal to 0.01 for each drug) and conjunctival injection (p less than or equal to 0.02 for each drug), when compared to contralateral eyes receiving PBS. When compared to 0.3% pheniramine in the fellow eye (mean difference score = 0.79 +/- 0.21), 0.3% chlorpheniramine (1.5 +/- 0.22; p = 0.04) and 0.3% dexbrompheniramine (1.71 +/- 0.18; p = 0.01) were superior in decreasing histamine-induced itching. Dose-response curves demonstrated that 0.4% and 0.5% pheniramine were statistically superior to 0.3% in relieving itching and redness. Compared to 0.3% pheniramine, 0.1% and 0.2% chlorpheniramine and 0.2% pyrilamine were statistically superior in inhibiting redness and itching. The results of this study suggest that 0.1%, 0.2% and 0.3% chlorpheniramine, 0.3% dexbrompheniramine, 0.2% pyrilamine, and 0.4% and 0.5% pheniramine were effective in relieving the itching and conjunctival injection associated with topically applied histamine. These seven formulations should be considered as possible new preparations for use as ophthalmic antihistamines and may warrant further evaluation.
To evaluate antiallergic agents, we conducted five allergen challenge studies of increasing refinement. The final study design that evolved included two baseline visits, when skin test-positive subjects were administered a bilateral ocular allergen challenge. At the first visit, the threshold dose of reactivity was determined by increasing allergen doses at 10-minute intervals. At the second baseline visit, 3 days later, the responsive subjects were challenged with the final, highest dose used on visit 1 to assure that the allergic reaction was reproducible and not a cumulative effect of multiple allergen doses. The responsive subjects then returned 3 days later for the drug efficacy evaluation. After a slit-lamp examination, subjects were pretreated with the test drug in one eye and the placebo in the fellow eye in a randomized, double-masked fashion. After 10 minutes, subjects were challenged bilaterally with the allergen dose identified on the previous visits. Postchallenge evaluations of hyperemia, itching, chemosis, eyelid swelling, and tearing were performed at 3, 10, and 20 minutes. Subjects were rechallenged 4 hours after drug administration to assess duration of action. Slit-lamp examinations were again performed at the same intervals as after the initial challenge. A total of 396 subjects were given a baseline allergen challenge; 83.6% responded with a moderate (2+) ocular allergic reaction. Of the 266 given a second baseline challenge, 87.2% responded positively again, suggesting that ocular challenge was highly correlated with skin reactivity and reproducible with a second challenge. No statistically significant difference in redness and itching was found when both eyes were challenged with the same dose of allergen.(ABSTRACT TRUNCATED AT 250 WORDS)
The ophthalmic combination product of 0.05% naphazoline hydrochloride and 0.5% antazoline phosphate (Vasocon-A) was evaluated as an antiallergic agent in 100 subjects with a known allergic history to cat dander, ragweed, or bluegrass pollen. Three independent study sites were used. The allergen challenge model of acute allergic conjunctivitis was selected to assess the agent as it provided a standardized and precise way to measure drug effectiveness for this indication. In a double-masked randomized fashion, the subjects were assigned to one of three groups that received one drop of Vasocon-A in one eye and one drop of either 0.05% naphazoline (group 1), 0.5% antazoline (group 2), or placebo (group 3) in the contralateral eye. After 10 minutes, the dose of allergen shown to elicit a 2+ redness and itching reaction was instilled bilaterally. Signs and symptoms of allergic conjunctivitis were evaluated after 3, 5, and 10 minutes. Subjects were then rechallenged 2 hours after drug administration to assess the duration of action of the agents. Vasocon-A was found to significantly inhibit all five major signs and symptoms of allergic conjunctivitis: itching, redness, chemosis, lid swelling, and tearing, for more than 85% of the comparisons when compared over time with placebo, naphazoline alone, or antazoline alone. The results of this study indicate that the combination of naphazoline and antazoline was more effective in inhibiting redness than naphazoline and more effective in inhibiting itching than antazoline. These findings support the use of such a combination for the treatment of allergic conjunctivitis.
Tryptase, a neutral endoprotease, is secreted by activated mast cells in human tissues. Tryptase levels in various body fluids have been used as an indicator of mast cell activation. The authors determined tryptase levels in unstimulated tears collected from the following groups of patients: (1) normal control, (2) nonallergic ocular inflammation, (3) asymptomatic seasonal allergic conjunctivitis, (4) symptomatic seasonal allergic conjunctivitis, (5) vernal conjunctivitis, and (6) contact lens-associated giant papillary conjunctivitis. They also assessed the release of tryptase into the tear fluid after provoking the conjunctiva with (7) allergens, (8) compound 48/80, and (9) rubbing. Tryptase levels were elevated in tears of patients with active ocular allergy and also increased after provoking the conjunctiva with allergens in atopic subjects and with compound 48/80 and rubbing in nonatopic subjects. Tryptase levels in tear fluid may prove useful as a clinical indicator of mast cell involvement in ocular allergic disorders. In provocation experiments, tryptase levels may be used to evaluate and compare different mast cell stabilizing agents.
The effects of altering the eicosanoid precursor pool on several aspects of the nonimmunologically mediated inflammatory and angiogenic processes that follow 1N and 4N NaOH alkali burning of the rabbit cornea were compared with controls. Diets were supplemented with several dosages of oils containing either gamma-linolenic acid (GLA) (borage oil), eicosapentaenoic acid (EPA) (sardine oil), or a combination of the two in a dose-response protocol. Significant changes in serum fatty acid composition were demonstrated. Gamma-linolenic acid proved consistently superior to EPA in modulating the neovascular response judged by three neovascular indices. At 14 days, GLA significantly reduced the polymorphonuclear leukocyte and macrophage inflammatory infiltrate and EPA reduced the macrophage component, both with high dose; EPA also reduced keratocyte proliferation. Wound-healing parameters were unaffected. Evidence for GLA-EPA synergism was modest. Prolonged neovascular responses and chronic inflammation occurring in the clinically relevant context of severe structural damage can be modulated by nutritional alteration of the eicosanoid precursor pool.
One hundred and seventy-eight patients undergoing uncomplicated cataract extraction with posterior chamber intraocular lens insertion completed a prospective, randomized, controlled trial of oral piroxicam in the prophylaxis of postoperative cystoid macular edema (CME), with a 1-year follow up. The incidence of "visually significant" CME, the mean interval to onset following surgery, clinical severity, recurrence rate, and the time to achieve best corrected visual result were unaffected by a 17-day piroxicam course. Oral steroid CME treatment produced a rapid response, but could not be shown to change the ultimate visual results. High-performance liquid chromatography analysis of aqueous humor obtained at cataract surgery suggested that piroxicam's pharmacokinetics might be a factor in this lack of response; the large number of potential inflammatory mediators uninfluenced by cyclo-oxygenase inhibition also may implicate piroxicam pharmacodynamics.
Compound 48/80, a non-immunogenic mast cell degranulatory agent, is known to produce the signs and symptoms of ocular allergy. Maximal mast cell degranulation of human conjunctiva occurred within the first hour after stimulation by a single topical dose of compound 48/80 (20 microliters, 7.5 mg/ml). The average percentage of fully degranulated mast cells in treated specimens (n = 9) was 31% (range 5-60%) versus 6% (range 0-20%) in control specimens (n = 5). Exact correlates of representative granulated, partially degranulated, and fully degranulated mast cells were determined by light and transmission electron microscopy.
Cellular events in the rat conjunctiva were studied at 1, 6 and 24 h following the topical application of leukotriene B4. A significant increase was noted in the number of eosinophils (p less than 0.01) and neutrophils (p less than 0.05) at 1 h and only in eosinophils at 6 h after leukotriene B4 application at the 2-micrograms dose. At the 200-ng dose, the eosinophil count was significantly elevated at 1 h only, and the number of neutrophils was not significantly changed at any time point. No significant increase in cell counts was observed at the 20-ng dose. In conclusion, certain doses of topically applied leukotriene B4 significantly increased the number of eosinophils and neutrophils in the rat conjunctiva.
Central corneal alkali burn injuries were induced in rabbits by applying five NaOH concentrations on uniformly soaked 7 mm filter paper discs. Clinical parameters were evaluated daily by microscopic examination and photography, and corneal myeloperoxidase levels were measured periodically. Satisfactory alkali burn models of corneal inflammation, vascularization and ulceration were developed by manipulating the alkali concentration.
Complete records from 175 patients with 176 episodes of culture-proven bacterial keratitis treated over a 4-year period at the Massachusetts Eye and Ear Infirmary in Boston were analyzed. Sixty-three percent of the infections involved gram-positive organisms, and 40% involved gram-negative organisms; 15% were polymicrobial. There was a high incidence of infection with Staphylococcus aureus (28%), coagulase-negative staphylococci (14%), diphtheroids (14%), Pseudomonas aeruginosa (14%), and Streptococcus pneumoniae (12%). Gram stain correlation was achieved in 55%. Potential predisposing factors, usually multiple, were identified in 97% of the patients. Fifty percent of the ulcers were associated with such iatrogenic factors as prior topical corticosteroid therapy, penetrating keratoplasty, and contact lens use. Trauma occurred in only 16%. Several statistically significant associations of epidemiologic factors and outcome variables were revealed. Ninety-five percent of the ulcers resolved with therapy, but only 44% of the patients had visual acuity better than the level at admission, and 13% developed major complications.
The ability of hyaluronidase to improve akinesis in retrobulbar anesthesia was evaluated in a double-masked study. Forty consecutive patients undergoing cataract surgery were anesthetized with 3 ml of a 1:1 mixture of 4.0% lidocaine and 0.75% bupivacaine solution. In a predetermined randomized fashion, 2 ml of hyaluronidase (300 USP units) were added to half of the syringes, and 2 ml of saline to the remaining half. The level of akinesia was graded in six different positions of gaze. Seventy percent of the hyaluronidase group exhibited complete akinesis, while only 40% of the control group did. The mean scores for four out of six positions of gaze were significantly higher in the hyaluronidase patients than in the control group. Similarly, the hyaluronidase subjects showed a significantly higher sum score for the six sectors than did the control subjects (p = .0001). These results show that hyaluronidase significantly enhances akinesia. It is therefore recommended that it be included in the anesthetic regimen for such surgeries.