Mark A. Hurst

The Roche European American Cataract Trial (REACT): A randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract

context Funding surgery worldwide for age-related cataract (ARC), a leading cause of blindness, is a huge economic burden. Non-surgical means of slowing ARC progression could benefit patients and reduce this burden. objective To determine if a mixture of oral antioxidant micronutrients [mg/day] (ß-carotene [18], vitamin C [750], and vitamin E [600]) would modify progression of ARC. design REACT was a multi-centered, prospective, double-masked, randomized, placebo-controlled, 3-year trial. setting Consecutive adult American and English outpatients with early ARC were recruited. patients Four-hundred-and-forty-five patients were eligible; 297 were randomized; 231 (78%) were followed for two years; 158 (53%) were followed for three years; 36 (12%) were followed for four years. Twelve patients died during the trial (9 on vitamins; 3 on placebo (p = 0.07)). There were no serious safety issues. intervention After a three-month placebo run-in, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months. main outcome measure Cataract severity was documented with serial digital retroillumination imagery of the lens; progression was quantified by image analysis assessing increased area of opacity. This measure of area, ‘increase % pixels opaque’ (IPO), was the main outcome measure. results There were no statistically significant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up times by treatment group were the same. After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent (p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically significant benefit of treatment in the U.K. group. In spite of nearly perfect randomization into treatment groups, the U.S. and U.K. cohorts differed significantly. conclusion Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC.

Validation of methods for the assessment of cataract progression in the Roche European-American AnticataractTrial (REACT)

The Roche European-American Anticataract Trial (REACT) will assess the effect of antioxidants on progression of cataract in humans. This report evaluates the methods used in REACT. Seventy three subjects (139 eyes) with cortical (C), posterior subcapsular (P), nuclear (N) or mixed cataract were seen twice within two weeks for eye examinations, assessments of visual function, lens photographs and CCD images. The degree of cataract and nuclear color (NC) were assessed with subjective (LOCS III) and objective (computerized, CASE 2000 CCD) methods. Repeat visit values were used to calculate intraclass correlation coefficients (r1) and 95% tolerance limits (TL). A clinically significant change (CSC) was defined as one step in LOCS III. The relative power of each method to detect cataract change and sample sizes needed to achieve statistically significant results were calculated. The r1 values for visual function tests ranged from 0.76 to 0.88; if these tests of visual function were used to detect a clinically significant change in cataract severity, sample sizes of 840 to 2707 per group would be needed. The r1 values for LOCS III were 0.88 to 0.97, and sample sizes ranged from 50 to 135 per group. The r1 values for the CCD were 0.93 to 0.98, and sample sizes ranged from 1 to 42 with poorer values relating to measurement of P. We conclude that the methods used in REACT are reproducible. The analytical algorithms in the image analysis programs did not permit differentiation between C and P opacification; therefore, P cataract is best measured with LOCS III. REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year between the mean rates of cataract progression in two groups.

Reliability of drop size from multi-dose eye drop bottles : Is it cause for concern?

Purpose Responses to topically applied ocular drugs vary between patients. The volume of drug instilled is of particular importance as one of many sources of response variation, but the reliability of drop volume from eye drop bottles is unknown. Hence, the repeatability of drop volume and factors affecting this for a variety of drug manufacturers were considered in this study.Methods Nineteen bottles, one from each primary manufacturer in the UK, were examined. The mass of all drops expelled from each bottle was measured with respect to the bottle type, handling angle, drop number, drug and concentration. The accuracy (repeatability and trueness) of drops from each bottle was also evaluated.Results Drop volume varied significantly between drug manufacturers, ranging from 33.8 µl to 63.4 µl. The handling angle of the bottle also influenced drop volume, with angles less than 60° giving smaller drops. Drop number exhibited no significant effect upon drop volume. However, the drug type and its concentration did significantly affect the volume of the drop expelled from the bottle, with higher concentrations giving rise to larger drops. Repeatability coefficients across the range of bottles varied between ± 2.24 µl and ± 10.76 µl (mean ± 5.07 µl).Conclusions It is well reported that drug volume instilled has a significant effect on the degree of response. However, there are currently no official regulations concerning eye drop volume in either the UK or the USA. Since drop volume has been shown to vary significantly depending upon a variety of factors, it may be appropriate that the regulatory bodies consider the consequences of variable drop size.

A novel system for the objective classification of iris colour and its correlation with response to 1% tropicamide

Iris colour can provide an enormous amount of information about an individual. In addition to changes with pathological conditions, the colour of the iris can be a particularly useful indicator of how well a person will respond to a topically applied ocular drug. Until recently, classification of iris colour has been subjective, ranging from a basic description (‘light’ and ‘dark’) to more detailed grading systems, such as a comparison with preset photographic standards. However, variability within observers and differences in the interpretation between observers can influence the results. Objective techniques, in this respect, possess several advantages. They are able to detect differences in colour that subjective techniques are incapable of and they provide continuous data rather than discrete categories, thus improving the accuracy of drug response predictions. This study assessed iris colour by objective means. Slit‐lamp photographs of various coloured irides were taken under standardised conditions. The slides were then scanned into a computer and the colour analysed using a calibrated software package. To establish the optimum colour parameter to be used for predictions of drug response, several parameters were calculated and compared with the subject response to 1% tropicamide (maximum change in pupil size, time to maximum change and total duration of effect). Many parameters had strong correlations with drug response, but the parameters ‘z’, ‘b’ (the proportion of blue in the image) and ‘y’ (the proportion of yellow in the image) were found to exhibit the highest correlations. They also showed better correlations with drug response than did a current iris colour grading system.

Eye drop container delivery: a source of response variation?

Variations in response to topically applied ocular drugs (e.g. mydriatics and cycloplegics) and their possible aetiology have been studied previously. It appears that individual patient differences, external influencing factors and the characteristics of the particular drug may all govern the response. One factor worthy of note in this regard is the possibility of variation in the drug volume instilled. Single-use eye drop containers known as Minims are commonly used during ophthalmic diagnostic procedures. However, in this study the drop volume was shown to vary considerably, depending upon the angle at which the Minims container was held, the particular drug and the number of drops previously expelled from the unit.

The subjective assessment of cataract

The medical treatment of cataract now appears to be a distinct possibility. A number of anti‐cataract formulations are being clinically tested, and more clinical trials are being planned. To obtain a true assessment of a drugs efficacy, a battery of tests are needed which can accurately assess cataract progress. A clinical trial of the proposed anti‐cataract drug Bendalina is being conducted. The six subjective methods used to assess cataract progression in the trial are presented. These are refractive error, LogMAR visual acuity, contrast sensitivity, glare sensitivity, retinal visual acuity and displacement threshold hyperacuity. The reasons for using each technique and their method of measurement is explained.

Validating a "pillar and collar" technique for measuring the edge lift of rigid contact lenses.

Purpose. The clinical importance of the edge lift of rigid contact lenses is often neglected, possibly due to previous difficulties in its measurement. A new method of measuring axial edge lift (AEL) and radial edge lift (REL) using standard contact lens verification equipment, such as an optical spherometer, a thickness gauge, and contact lens V gauge, is described. Methods. The technique was validated for trueness (accuracy) and precision (repeatability) by measuring the edge lift of a number of monocurve lenses, manufactured both with and without a normal edge finish. Results. Edge lift was measured to an accuracy of 0.01 mm. Conclusions. As long as a mean of eight independent measurements of back optic zone radius (BOZR), sagitta, and one measurement of center thickness are taken, the pillar and collar technique is capable of producing accurate and repeatable measurements of the edge lift of a rigid contact lens.

Pillar and collar technique for measuring the axial edge lift of multicurve rigid lenses

Background. The method of using an optical spherometer and a lens thickness gauge, in combination with a pillar and collar, has previously been shown to be repeatable and accurate (to 0.01 mm) in measuring the edge lift of rigid monocurve lenses. Purpose. This paper goes on to validate the technique for measurements taken on edge-finished multicurve rigid lenses. Methods. The axial edge lift (AEL) of a series of multicurve rigid lenses having known values of AEL was measured using an optical spherometer, a thickness gauge, and contact lens V gauge in a similar way as was described in the companion paper. Results. The results show that as long as a correction factor of 0.01 mm is applied, as found in the previous paper, the technique will allow satisfactory verification of the edge lift. Conclusions. The technique is accurate and reproducible, even in multicurve lens designs, provided that a calibrating correction factor of 0.01 mm is applied to account for methodological error. It will also indirectly allow the accuracy of manufacture of the peripheral curves and diameters of any rigid contact lens to be verified.

Optimal temporal frequencies in oscillatory movement hyperacuity measurements of visual function in cataract patients

Hyperacuity tasks have been suggested for the assessment of potential visual function in the presence of cataracts. To test this suggestion, hyperacuity thresholds for an oscillating bar were measured in 30 subjects with idiopathic cataract and in 24 age-matched normals over a range of oscillation frequencies. Each subjects cataract was categorized using the Oxford Clinical Cataract Classification and Grading System. Cataract was found to have a significant effect on thresholds, although a differential morphological effect on thresholds was equivocal. Thresholds at higher temporal frequencies were significantly raised when compared to the normal group. The main conclusion to be drawn from this study is that motion hyperacuity thresholds appear unaffected by cataract at low oscillation frequencies and should be used in preference to higher frequencies in the assessment of such patients.

Contact lens opacity grading system (CLOGS)

Abstract Grading and classification systems have been used in contact lens research for many years, despite a lack ofstandardisation. A new system for classifying the type of contact lens deposit and assessing its extent is presented. It makes use of five standard photographs for direct comparison purposes and allows decimal interpolation between grades. A further five photographs are included to allow differential identification of artefacts, scratches and spot deposits. This paper presents both intraobserver (coefficients of repeatability ±0.79, ±0.79 and ±0.76; Pearson correlation coefficients 0.94, p p p p p p