Mark B Abelson

Harvard Medical School, Boston, Massachusetts, United States

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Publications (146)480.16 Total impact

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    ABSTRACT: Purpose. To develop an automated method of grading fluorescein staining that accurately reproduces the clinical grading system currently in use. Methods. From the slit lamp photograph of the fluorescein-stained cornea, the region of interest was selected and punctate dot number calculated using software developed with the Opencv computer vision library. Images (N=229) were then divided into six incremental severity categories based on computed scores. The final selection of fifty-four photographs represented the full range of scores: nine images from each of six categories. These were then evaluated by three investigators using a clinical 0-4 corneal staining scale. Pearson correlations were calculated to compare investigator scores, and mean investigator and automated scores. Lin's Concordance Correlations (CCC) and Bland Altman plots were used to assess agreement between methods and between investigators. Results. Pearson's correlation between investigators was 0.914; mean CCC between investigators was 0.882. Bland-Altman analysis indicated that scores assessed by Investigator 3 were significantly higher than those of Investigators 1 and 2 (paired t-test). The predicted grade was calculated to be: Gpred=1.48log(Ndots) - 0.206. The two-point Pearson's correlation coefficient between the methods was 0.927 (p<0.0001). CCC between predicted automated score Gpred and mean investigator score was 0.929, 95% C.I. (0.884, 0.957). Bland-Altman analysis did not indicate bias. The difference in standard deviation between clinical and automated methods was 0.398. Conclusion. An objective, automated analysis of corneal staining provides a quality assurance tool to be used to substantiate clinical grading of key corneal staining endpoints in multi-centered clinical trials of dry eye. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
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    ABSTRACT: To classify blinks in dry eye and normal subjects into six subtypes, and to define the blink rate and duration within each type of blink, as well as the total lid-contact time/minute. This was a single-centered, prospective, double-blind study of eleven dry-eye and ten normal subjects. Predefined subjects watched a video while blinks were recorded for 10 minutes. Partial blinks were classified by percentage closure of maximal palpebral fissure opening: 25%, 50%, 75%. Complete blinks were characterized as full (>0 seconds), extended (>0.1 seconds), or superextended (>0.5 seconds). The mean duration of each type of blink was determined and standardized per minute as total lid-contact time. Total blinks observed were 4,990 (1,414 normal, 3,756 dry eye): 1,809 (50.59%) partial and 1,767 (49.41%) complete blinks among dry-eye subjects versus 741 (52.90%) partial and 673 (47.60%) complete blinks among normal subjects. Only superextended blinks of ≥0.5-second duration were significantly more frequent in dry-eye subjects than normals (2.3% versus 0.2%, respectively; P=0.023). Total contact time was seven times higher in dry-eye subjects than normals (0.565 versus 0.080 seconds, respectively; P<0.001). Isolating only extended blinks (>0.1 second), the average contact time (seconds) was four times longer in dry-eye versus normal subjects (2.459 in dry eye, 0.575 in normals; P=0.003). Isolating only superextended blinks (>0.5 seconds), average contact time was also significantly different (7.134 in dry eye, 1.589 in normals; P<0.001). The contact rate for all full closures was 6.4 times longer in dry-eye (0.045 versus 0.007, P<0.001) than normal subjects. Dry-eye subjects spent 4.5% of a minute with their eyes closed, while normal subjects spent 0.7% of a minute with their eyes closed. Contact time might play a role in the visual function decay associated with increased blink rates.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:869-74. DOI:10.2147/OPTH.S56783
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    ABSTRACT: We have observed that dry eye redness is characterized by a prominence of fine horizontal conjunctival vessels in the exposed ocular surface of the interpalpebral fissure, and have incorporated this feature into the grading of redness in clinical studies of dry eye. To develop an automated method of grading dry eye-associated ocular redness in order to expand on the clinical grading system currently used. Ninety nine images from 26 dry eye subjects were evaluated by five graders using a 0-4 (in 0.5 increments) dry eye redness (Ora Calibra™ Dry Eye Redness Scale [OCDER]) scale. For the automated method, the Opencv computer vision library was used to develop software for calculating redness and horizontal conjunctival vessels (noted as "horizontality"). From original photograph, the region of interest (ROI) was selected manually using the open source ImageJ software. Total average redness intensity (Com-Red) was calculated as a single channel 8-bit image as R - 0.83G - 0.17B, where R, G and B were the respective intensities of the red, green and blue channels. The location of vessels was detected by normalizing the blue channel and selecting pixels with an intensity of less than 97% of the mean. The horizontal component (Com-Hor) was calculated by the first order Sobel derivative in the vertical direction and the score was calculated as the average blue channel image intensity of this vertical derivative. Pearson correlation coefficients, accuracy and concordance correlation coefficients (CCC) were calculated after regression and standardized regression of the dataset. The agreement (both Pearson's and CCC) among investigators using the OCDER scale was 0.67, while the agreement of investigator to computer was 0.76. A multiple regression using both redness and horizontality improved the agreement CCC from 0.66 and 0.69 to 0.76, demonstrating the contribution of vessel geometry to the overall grade. Computer analysis of a given image has 100% repeatability and zero variability from session to session. This objective means of grading ocular redness in a unified fashion has potential significance as a new clinical endpoint. In comparisons between computer and investigator, computer grading proved to be more reliable than another investigator using the OCDER scale. The best fitting model based on the present sample, and usable for future studies, was [Formula: see text] is the predicted investigator grade, and [Formula: see text] and [Formula: see text] are logarithmic transformations of the computer calculated parameters COM-Hor and COM-Red. Considering the superior repeatability, computer automated grading might be preferable to investigator grading in multicentered dry eye studies in which the subtle differences in redness incurred by treatment have been historically difficult to define.
    Clinical ophthalmology (Auckland, N.Z.) 06/2013; 7:197-1204. DOI:10.2147/OPTH.S39703
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    ABSTRACT: The purpose of this study was to investigate the occurrence and duration of extended blinks ≥ 70 msec and their associated interblink intervals in normal subjects and in subjects with mild to moderate dry eye. This single-center, prospective, double-blind study included 11 subjects with dry eye and eight subjects with normal eyes. Extended blinks were defined as lid closure in at least two successive video frames (≥70 msec). Digital video imaging of each subject's eyes was recorded while the subject viewed a 10-minute documentary. The subjects did not know that blink was the outcome being measured. Following capture, the videos were manually analyzed in a masked fashion for the occurrence of extended blinks. The length of the interblink interval (ie, time between blinks) before and after these extended blinks (the interblink interval ratio) was calculated, as well as differences in lid contact times. The dry eye group had a median extended blink duration which was 2.53 times longer than that of the normal group. For subjects with dry eye, interblink intervals post-extended blink were significantly longer than interblink intervals pre-extended blink (P < 0.001). Interblink intervals did not lengthen significantly in normal subjects. In both groups, the duration of the extended blink was significantly (P = 0.001) and positively correlated with interblink interval ratio (post-extended to pre-extended blink interblink interval), such that for each doubling of extended blink duration, the interblink interval ratio increased by 10%. Blinks longer than one second in duration occurred almost exclusively in subjects with dry eye. THIS STUDY REPORTS THREE CENTRAL FINDINGS: blink duration tended to be longer in subjects with dry eye; a lengthening of the interblink interval after an extended blink occurred in subjects with dry eye but not in those without dry eye; and a longer blink duration was associated with a significantly increased interblink interval ratio in all subjects.
    Clinical ophthalmology (Auckland, N.Z.) 02/2013; 7:337-42. DOI:10.2147/OPTH.S39356
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    ABSTRACT: Our aim was to extend the concept of blink patterns from average interblink interval (IBI) to other aspects of the distribution of IBI. We hypothesized that this more comprehensive approach would better discriminate between normal and dry eye subjects. Blinks were captured over 10 minutes for ten normal and ten dry eye subjects while viewing a standardized televised documentary. Fifty-five blinks were analyzed for each of the 20 subjects. Means, standard deviations, and autocorrelation coefficients were calculated utilizing a single random effects model fit to all data points and a diagnostic model was subsequently fit to predict probability of a subject having dry eye based on these parameters. Mean IBI was 5.97 seconds for normal versus 2.56 seconds for dry eye subjects (ratio: 2.33, P = 0.004). IBI variability was 1.56 times higher in normal subjects (P < 0.001), and the autocorrelation was 1.79 times higher in normal subjects (P = 0.044). With regard to the diagnostic power of these measures, mean IBI was the best dry eye versus normal classifier using receiver operating characteristics (0.85 area under curve (AUC)), followed by the standard deviation (0.75 AUC), and lastly, the autocorrelation (0.63 AUC). All three predictors combined had an AUC of 0.89. Based on this analysis, cutoffs of ≤3.05 seconds for median IBI, and ≤0.73 for the coefficient of variation were chosen to classify dry eye subjects. (1) IBI was significantly shorter for dry eye patients performing a visual task compared to normals; (2) there was a greater variability of interblink intervals in normal subjects; and (3) these parameters were useful as diagnostic predictors of dry eye disease. The results of this pilot study merit investigation of IBI parameters on a larger scale study in subjects with dry eye and other ocular surface disorders.
    Clinical ophthalmology (Auckland, N.Z.) 01/2013; 7:253-9. DOI:10.2147/OPTH.S39104
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    ABSTRACT: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye. Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3. Those who met the ocular redness and itching criteria were randomized to receive either the controlled adverse environment (CAE) challenge (group A, n = 9) or no challenge (group B, n = 8) at day 6. Thirty minutes after CAE/no-CAE, subjects were challenged with allergen and their signs and symptoms graded. Exploratory confocal microscopy was carried out in a subset of subjects at hourly intervals for 5 hours post-CAC on days 3 and 6. Seven minutes post-CAC, subjects exposed to the CAE had significantly greater itching (difference between groups, 0.55 ± 0.25, P = 0.028), conjunctival redness (0.59 ± 0.19, P = 0.002), episcleral redness (0.56 ± 0.19, P = 0.003) and mean overall redness (mean of conjunctival, episcleral, and ciliary redness, 0.59 ± 0.14, P < 0.001). The mean score at 7, 15, and 20 minutes post-CAC for conjunctival redness (0.43 ± 0.17, P = 0.012), episcleral redness (0.49 ± 0.15, P = 0.001), mean overall redness in all regions (0.43 ± 0.15, P = 0.005), and mean chemosis (0.20 ± 0.08, P = 0.017) were also all significantly greater in CAE-treated subjects. Confocal microscopic images of conjunctival vessels after CAC showed more inflammation in CAE-treated subjects. In subjects with both dry eye and allergic conjunctivitis, exposure to adverse environmental conditions causes an ocular surface perturbation that can intensify allergic reactions.
    Clinical ophthalmology (Auckland, N.Z.) 01/2013; 7:157-65. DOI:10.2147/OPTH.S38732
  • P. Gomes, M.B. Abelson
    Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB190. DOI:10.1016/j.jaci.2011.12.274 · 11.25 Impact Factor
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    ABSTRACT: This clinical trial evaluated the safety and effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo for the treatment of ocular itching and conjunctival hyperemia (redness) using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis when dosed 16 h before a CAC test. Subjects with a history of allergic conjunctivitis were assigned to receive placebo or bepotastine besilate ophthalmic solution 1.0% or 1.5% in a single-center, randomized, placebo-controlled clinical trial. Eligible subjects (n=107) aged 10 years and older with a history of allergic conjunctivitis who had a reproducible positive reaction to a CAC were enrolled and dosed with test agent. The primary trial objectives included assessment of ocular itching and conjunctival redness at 16 h after instillation of test agent. Reductions in several CAC-induced secondary symptoms and signs of allergic conjunctivitis were also evaluated for tearing, ciliary and episcleral redness, eyelid swelling, chemosis, and mucous discharge. Bepotastine besilate ophthalmic solution 1.5% demonstrated clinical effectiveness and statistical significance in comparison to placebo for the reduction in CAC-induced ocular itching 16 h after drug administration. Bepotastine besilate ophthalmic solution 1.0% also achieved statistical significance in comparison to placebo for reducing ocular itching at all time points 16 h after dosing. Statistically significant reduction (P≤0.05) was additionally seen in this CAC test for the secondary ocular efficacy variable of allergen-induced tearing for bepotastine besilate ophthalmic solution 1.5%. No clinical benefit was seen for reducing the coprimary efficacy variable of conjunctival redness with the CAC model of allergic conjunctivitis. Bepotastine besilate ophthalmic solution 1.5% produced predefined clinically meaningful reduction in CAC-induced ocular itching and tearing in a single-site trial and was more effective than bepotastine besilate ophthalmic solution 1.0% and placebo for reducing ocular itching in a CAC test 16 h after dosing.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 06/2011; 27(4):385-93. DOI:10.1089/jop.2011.0005 · 1.42 Impact Factor
  • Mark B Abelson, James T McLaughlin, Paul J Gomes
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    ABSTRACT: Use of topical antihistamines in the treatment of allergic conjunctivitis has evolved over the past several decades as our knowledge of the nature of the underlying disease has progressed. Formulations for the eye typically employ H(1)-receptor antagonists with a dual action, both directly as competitors for histamine receptor occupancy and as mast cell-stabilizing agents. Many of these compounds also display activity against late-phase allergic symptoms. Of the newest available drugs, several have a prolonged duration of action allowing once-daily dosing. Future development is likely to focus on long-acting agents such as these and on drugs that can target additional histamine receptor subtypes.
    Current Allergy and Asthma Reports 03/2011; 11(3):205-11. DOI:10.1007/s11882-011-0188-5 · 2.45 Impact Factor
  • M. B. Abelson, P. Gomes, N. Arenas
    Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.1009 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.1016 · 11.25 Impact Factor
  • P. Gomes, M. B. Abelson, E. Angjeli
    Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.220 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.1022 · 11.25 Impact Factor
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    ABSTRACT: To evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo at reducing ocular itching and conjunctival hyperemia in the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Prospective, double-masked, randomized, placebo-controlled, phase 3 CAC clinical trial. This multicenter trial enrolled 130 subjects with a clinical history of allergic conjunctivitis who were randomized to bepotastine besilate ophthalmic solution 1.0%, 1.5%, or 0.0% (placebo). One drop of test agent was instilled bilaterally before a CAC test evaluating responses at 15 minutes, 8 hours, or 16 hours after test agent instillation. Primary efficacy outcomes were unit improvements relative to placebo in mean scores for ocular itching and conjunctival hyperemia, each graded on 0- to 4-unit scales. Reductions of 1.2 units or more in mean ocular itching scores at all time points for both bepotastine besilate ophthalmic solutions 1.0% and 1.5% were observed at onset of action and 8-hour duration-of-action CAC tests (P < .0001). Statistically significant reductions in conjunctival hyperemia (P < or = .0125) were observed for bepotastine besilate ophthalmic formulations only at the onset of action CAC test. Bepotastine besilate ophthalmic solutions 1.0% and 1.5% both substantially decreased CAC-induced ocular itching for at least 8 hours after dosing. Reductions in conjunctival hyperemia after a CAC, although statistically significant for bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo when assessed at 15 minutes after dosing, were modest.
    American Journal of Ophthalmology 07/2010; 150(1):122-127.e5. DOI:10.1016/j.ajo.2010.02.007 · 4.02 Impact Factor
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    ABSTRACT: Bepotastine besilate is a selective histamine1-receptor antagonist and mast cell stabilizer with inhibitory effects on eosinophilic activity. To evaluate the safety and efficacy of 1.5% bepotastine besilate ophthalmic solution in alleviating nonocular symptoms induced by a conjunctival allergen challenge (CAC), a clinical model of allergic conjunctivitis. This was a single-center, double-masked, randomized, placebo-controlled clinical trial performed from March 1 to April 4, 2007. Patients 10 years or older with a history of allergic conjunctivitis and a reproducible, positive, clinical response to a CAC were eligible. Patients received either placebo or 1.5% bepotastine besilate, 1 drop in each eye. After 15 minutes, 8 hours, or 16 hours after dosing, a CAC was performed and patients evaluated nonocular symptoms using standardized grading scales. Seventy-one patients were enrolled in the study, and 66 comprised the per protocol population. A clinically meaningful reduction (> or = 1.0 unit) compared to placebo was achieved for rhinorrhea and nasal congestion at most time points after 1.5% bepotastine besilate instillation at 8 hours before a CAC test. Significant reductions (P < or = .05) in mean values were seen with 1.5% bepotastine besilate at 15 minutes and 8 hours after dosing for CAC-induced nasal congestion, rhinorrhea, ear or palate pruritus, nasal pruritus, and summed nonocular composite symptom (NOCS) scores and also at 16 hours after dosing for nasal congestion and rhinorrhea. The 1.5% bepotastine besilate formulation produced statistically significant reductions after a CAC in individual nonocular symptoms and NOCS scores at onset of allergic response and for at least 8 hours after instillation, with the greatest reduction seen for nasal congestion and rhinorrhea.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2010; 105(1):57-64. DOI:10.1016/j.anai.2010.04.005 · 2.75 Impact Factor
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    ABSTRACT: Subjects with dry eye often complain of disturbances in visual function and worsening of symptoms in the evening. To clinically substantiate these reports of diurnal variations, the present study tested subjects with dry eye on a series of visual function and ocular physiology measures. Twenty-one subjects with dry eye were enrolled and underwent ophthalmic examinations, including best spectacle-corrected visual acuity, visual function decay as measured by the interblink interval visual acuity decay test without ocular anesthetic, reading rate test, slit-lamp biomicroscopy, and tear film breakup time. Keratitis, conjunctival redness, and corneal sensitivity were also assessed. Examinations occurred once during the morning and for a second time in the evening. Subjects also completed a modified version of the Ocular Surface Disease Index at both study visits. Subjects with dry eye showed impaired visual function in the evening, as compared to that in the morning; they maintained their best spectacle-corrected visual acuity for a shorter time between blinks (P < 0.01) and had longer readings times (P < 0.05) in the evening as compared with that in the morning. These findings were qualified by Ocular Surface Disease Index results showing greater subjective visual impairment in the evening. Subjects also demonstrated a significant increase in keratitis and conjunctival redness from morning to evening testing. Less ocular discomfort was reported in the evening than in the morning; this effect significantly correlated with corneal sensitivity in the evening. Subjects with dry eye experience significant diurnal variations of visual function and ocular surface physiology. These daily rhythms should be considered when designing clinical trials and when quantifying disease severity.
    Cornea 06/2010; 29(6):607-12. DOI:10.1097/ICO.0b013e3181c11e45 · 2.36 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2010; 125(2). DOI:10.1016/j.jaci.2009.12.181 · 11.25 Impact Factor
  • M. B. Abelson, P. Gomes, R. Chaturvedi
    Journal of Allergy and Clinical Immunology 02/2010; 125(2). DOI:10.1016/j.jaci.2009.12.406 · 11.25 Impact Factor
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    ABSTRACT: Purpose: Bepotastine besilate ophthalmic solution 1.5% is an anti-allergic medication under investigation in the United States with selective histamine H1 receptor antagonistic action, stabilization of mast cell function, and inhibitory action on eosinophilic infiltration to inflammatory sites. The purpose of this clinical trial was to evaluate the safety of bepotastine besilate ophthalmic solution 1.5% dosed twice daily in a healthy pediatric population from 10-17 years of age. Methods: The clinical trial randomization was at a ratio of 2:1 (active:vehicle). The clinical trial was a multi-center, randomized, masked, 6-week safety study involving 4 study visits with 2 treatment groups, bepotastine besilate ophthalmic solution 1.5% and placebo. Pediatric subjects as young as 3 years of age represented approximately 15% of the 861 enrolled subjects. Both investigational products were dosed twice daily and the dosing compliance was monitored with dosing diaries. The number of healthy subjects from 10-17 years of age was distributed between bepotastine ophthalmic solution 1.5% (n=40) and placebo (n=15). Results: All enrolled pediatric subjects completed the study. The frequency of total adverse events (22.5% for bepostatine besilate ophthalmic solution 1.5%, 20.0% for placebo) and the absolute incidence of ocular adverse events (1 bepostatine besilate ophthalmic solution 1.5% subject, 2 placebo subjects) in subjects from 10-17 years of age were similar for both treatment groups. There also was no difference between treatment groups in this age range in IOP (P>0.65), visual acuity (P>0.73), or comfort (P>0.48). No severe adverse events were reported during the clinical trial. Conclusions: Bepotastine besilate ophthalmic solution 1.5% dosed twice daily for six weeks was safe with minimal adverse events in a healthy pediatric population from 10-17 years of age.
    2009 American College of Clinical Pharmacy Annual Meeting; 10/2009

Publication Stats

3k Citations
480.16 Total Impact Points

Institutions

  • 1977–2014
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1980–2013
    • Schepens Eye Research Institute
      Boston, Massachusetts, United States
  • 1994–2011
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2010
    • Massachusetts School of Law at Andover
      Andover, Massachusetts, United States
  • 1988–1989
    • Massachusetts Eye and Ear Infirmary
      • Department of Ophthalmology
      Boston, Massachusetts, United States
  • 1984
    • Tufts Medical Center
      • Division of Allergy
      Boston, Massachusetts, United States
  • 1981
    • University of Massachusetts Boston
      Boston, Massachusetts, United States