Measurement of flare intensity with the laser flare–cell meter is difficult and cumbersome to perform with a nondilated pupil because of light scatter from the iris. Therefore, most ophthalmologists dilate their patients' eyes before taking these measurements.1,2
Studies have found decreases in aqueous flare after application of tropicamide in normal patients.3–5 Only 1 study assessed the effect of mydriasis on aqueous flare in pseudophakic patients. Using a combination of tropicamide 0.5% and phenylephrine 0.5%, it found a significant decrease of about 20% after 3 hours.5
It is postulated that dilution of aqueous in the anterior chamber is the mechanism by which pupil dilation decreases aqueous flare5 because the protein content of the aqueous humor is thought to arise mainly in the anterior chamber.6,7 In the pseudophakic eye, the thin intraocular lens (IOL) in the capsular bag causes a large gap between IOL and iris under normal nonmydriatic conditions. Therefore, exchange of aqueous humor between the anterior and posterior chambers is constant. If dilation is the cause of flare decrease, one would predict that in the pseudophakic eye, pupil dilation would alter aqueous flare less than in the phakic eye. A direct pharmacological effect of the drug on uveal blood flow or aqueous flow could be another reason flare decreases after tropicamide application.
This study examined the effect of tropicamide on flare intensity under phakic and pseudophakic conditions and attempted to differentiate between the possible mechanisms of action of tropicamide on aqueous flare.
Patients and Methods
Twenty eyes of 20 patients with age-related cataract enrolled for cataract surgery were included in this prospective study. Preoperative exclusion criteria included uveitis, diabetes mellitus, history of ocular surgery or trauma, and other ocular disease thought to be relevant. Mean age was 77 years (range 57 to 91 years).
Aqueous flare and cells were measured with the Kowa FC-1000 laser flare–cell meter by the same investigator (V.P.) at the same time of day (3 to 6 pm). The measurement procedure was as follows: baseline measurement with a nondilated pupil, dilation with 1 drop of tropicamide 0.5% (Mydriaticum Agepha®), and subsequent measurements after 30, 90, and 180 minutes. These measurements were performed in the phakic eye on the day before surgery and in the pseudophakic eye on postoperative days 1, 3, 7, and 28. Measurements with a value of 0.0 or a difference between entry and exit signal of more than 8% were excluded. Mean values and standard deviations of 5 measurements were used.
Pupil diameter was recorded after each flare and cell measurement. The diameter was measured under constant light conditions with a ruler to the nearest 0.5 mm. Iris color was classified as brown, blue, gray, or green.
Before surgery, the pupil was dilated with 1 drop of tropicamide 0.5%, cyclopentolate 1%, and phenylephrine 2.5%. After a temporal clear corneal incision was made, a capsulorhexis was created. Next, phacoemulsification was performed and a silicone plate-haptic IOL (Staar AA4203VF) implanted in the capsular bag. All surgery was performed by the same surgeon (M.A.). Postoperative treatment included diclofenac (Voltaren Ophtha®) and betamethasone/neomycin (Betnesol N®) drops 4 times daily.
Data are presented as means ± SEM and ranges, indicating the minimums and maximums. Statistical analysis was done by analysis of variance and a repeated measures t test with a statistical software package (Statistica®). A P value of 0.01 was considered significant.
Mydriasis induced by tropicamide decreased aqueous flare preoperatively and on all postoperative days (Figure 1). Aqueous flare decreased constantly, reaching the maximum decrease at the last measurement after 180 minutes, although pupil diameter reached its maximum after 30 minutes. The decrease in flare was most pronounced on postoperative day 7 and least pronounced on postoperative day 1 (Figure 2).
Mydriasis induced by tropicamide had a different effect on aqueous cell count. Preoperatively and on postoperative day 1, there were no significant changes in cell count (P = .16 and P = .45, respectively). On all other postoperative days (3, 7, and 28), mydriasis decreased cell count (P < .05).
Distribution of iris color was as follows: 7 brown, 11 blue, 2 gray, and 1 green. There was no correlation between iris color and flare or cell results.
Tropicamide-induced mydriasis decreased aqueous flare by about 30%. The maximum decrease was reached after 3 hours. The magnitude of this maximum decrease was similar before and after cataract surgery except on postoperative day 1, when the decrease was less pronounced. In contrast, pupil diameter reached its maximum 30 minutes after application of tropicamide. Therefore, tropicamide's effect on pupil diameter has a different time course than its effect on aqueous flare.
The flare decrease induced by tropicamide in this study agrees with the findings of other studies. One found a 17% decrease 1.5 hours after application of tropicamide 0.4% in normal volunteers.4 Another found a 15% decrease 1 hour after tropicamide 1% in normal eyes.3 The only study that assessed the effect of mydriasis on aqueous flare in pseudophakic patients, using a combination of tropicamide 0.5% and phenylephrine 0.5%, found a significant decrease of about 20% after 3 hours.5
Our results suggest that protein dilution in the aqueous in the anterior chamber is not the main mechanism by which pupil dilation decreases aqueous flare. The protein content of the aqueous humor is thought to arise mainly from the iris root and iris vessels in the anterior chamber, not from the ciliary body in the posterior chamber.6,7 In the phakic patient, pupil dilation causes more exchange and mixture of aqueous between the anterior and posterior chambers, leading to protein dilution in the anterior chamber and therefore reduced flare.5 In our phakic patients before surgery, the pupil was maximally dilated after 30 minutes; however, the decrease in flare increased steadily until 3 hours after tropicamide application.
A pseudophakic eye with a thin IOL in the capsular bag has a large gap between the IOL and iris under normal nonmydriatic conditions. Therefore, exchange of aqueous humor between the anterior and posterior chambers is constant. We would predict that in the pseudophakic eye, pupil dilation would alter aqueous flare less than in the phakic eye if dilution were the mechanism of mydriasis-induced flare reduction. Our results, however, show that the relative reduction in flare after tropicamide pupil dilation in the pseudophakic eye is similar to the reduction before surgery. Therefore, it seems unlikely that the decrease in flare after pupil dilation is a consequence of the dilution.
Another possible reason for the flare decrease could be a decrease in background scatter from the iris as a result of dilation. Thus, a dilated pupil would present a more homogeneous background to the measurement site and result in less background scatter. Shah and coauthors3 found that background scatter decreases slightly with mydriasis; however, this decrease is not sufficient to explain the flare decrease.
A direct pharmacological effect of the drug is another possible reason for the flare decrease after tropicamide application. Tropicamide may increase aqueous humor formation or decrease anterior uveal blood flow, resulting in less protein transudation into the aqueous. It is possible that a pharmacological effect on blood flow reaches its maximum after a short time, as with pupil dilation. However, it takes longer to see the consequences of this change in flare intensity, which would explain the discrepancy between the time courses of pupil dilation and flare decrease. Also, the less pronounced decrease in flare after tropicamide application on the first postoperative day may be a consequence of the long-lasting effect of the cyclopentolate given preoperatively on the day of surgery.8
Because flare intensity measurement with the laser flare–cell meter is difficult and cumbersome to perform with a nondilated pupil because of light scatter from the iris, most ophthalmologists dilate their patients' eyes before measurement. We have shown that flare intensity decreases continuously with time after dilation, until 3 hours after application of the drop, the last time point at which we measured. Therefore, it is mandatory to use the same time interval between measurement and application of tropicamide to attain comparable and valid flare data. This holds for clinical trials using aqueous flare as an outcome variable and for clinical purposes, such as monitoring uveitis patients under therapy. Our data suggest that the ideal interval between tropicamide application and flare measurement is 3 hours. At this time, the relative reduction in flare was nearly identical preoperatively and on postoperative days 3, 7, and 28. Unfortunately, an interval of 3 hours is not suitable for daily clinical routine or for extensive clinical trials. We have no conclusive explanation for the rapid decrease in flare on postoperative day 7 compared with the other postoperative days.
In summary, tropicamide used for pupil dilation to enable easier measurement with the laser flare–cell meter decreases aqueous flare by about 30% within 3 hours. Tropicamide seems to decrease flare by pharmacological means, not by volumetric changes. Since flare decreases continuously within the first 3 hours after tropicamide application, the interval between drop application and measurement should be kept constant.
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