Abstract
Purpose
To examine the changes in the pupillary light response after phacoemulsification and to compare the difference in the response among patients in different age categories.
Study design
Prospective observational study.
Methods
Four-hundred twenty-two eyes of 422 patients in 3 age categories (60-69 years, 70-79 years, and 80-89 years) scheduled for phacoemulsification were consecutively enrolled. The eyes underwent examinations with an infrared pupillometer to obtain the parameters of the pupillary light response preoperatively and at 1 day and 1 and 3 months postoperatively. Differences in the parameters of the pupillary response were compared among 4 time intervals and the 3 age categories.
Results
The mean maximum and minimum pupillary diameters significantly decreased at 1 day postoperatively and returned to the preoperative level by 1 month postoperatively (P<.0001). The mean percentage of pupillary constriction was significantly reduced at 1 and 3 months postoperatively compared with preoperatively and at 1 day postoperatively (P<.0001). The average pupillary constriction and dilation velocities were significantly lower at 1 and 3 months postoperatively than they were preoperatively and at 1 day postoperatively (P<.0001). The latency to constriction did not differ significantly among the time intervals. The percentage of pupillary constriction was significantly smaller, and the average constriction and dilation velocities were lower in association with higher age categories at all time intervals (P≤.0185).
Conclusion
The pupillary light response was impaired several months after cataract surgery and worsened with increasing patient age, indicating that cataract surgery may compromise the pupillary constriction and dilation functions in association with age.
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Introduction
The pupillary response to light is governed by the antagonistic actions of the dilator and sphincter muscles in the iris, which are controlled by the sympathetic and parasympathetic nerves, respectively. The pupillary light response is diminished in patients with various optic nerve, retinal, and cerebral pathologies, including optic neuritis, glaucomatous optic neuropathy, age-related macular degeneration, retinitis pigmentosa, diabetes mellitus, and Alzheimer disease [1,2,3,4,5,6,7]. On the other hand, the impaired pupillary light response may also cause visual disturbances, including photophobia, photic phenomena, reduced peripheral vision, and reduced contrast sensitivity [8,9,10].
Cataract surgery is related to many aspects of the pupils. Because mydriasis is essential for performing cataract surgery, surgical procedures and pharmacologic agents to enlarge the pupil are used when pupillary dilation is inadequate [11,12,13]. Our previous study revealed that the pupillary diameter significantly decreases immediately after cataract surgery [14]. Whether the pupillary light response changes after cataract surgery, however, remains unclear. Peters and Tychsen [15] reported that the pupillary light response does not worsen after planned extracapsular cataract extraction, whilst Komatsu et al. [16] showed worsened pupillary constriction and dilation velocity after phacoemulsification. Additionally, whether the pupillary light response is impaired in association with age remains controversial [17,18,19,20,21,22]. In particular, whether the pupillary light response is altered after cataract surgery in association with patient age is unclear.
The present study investigated the longitudinal changes in the pupillary light response after cataract surgery using a large patient cohort and compared differences in the pupillary light response among different age categories. Because impairment of the pupillary light response leads to visual disturbances, including photic phenomena and deterioration of contrast sensitivity, an impaired pupillary light response may be clinically relevant, particularly in patients receiving multifocal intraocular lenses (IOLs).
Patients and methods
Study design
The present study was a prospective observational study conducted at the Hayashi Eye Hospital in Fukuoka, Japan, between April 24, 2019 and July 30, 2020. The study protocol was approved by the Institutional Review Board/Ethical Committee of the Hayashi Eye Hospital on April 23, 2019. All the participants received an explanation of the nature of the study and provided informed consent to participate. This study adhered to the tenets of the Declaration of Helsinki.
Participants
All consecutive patients who planned hospitalization to undergo phacoemulsification surgery and IOL implantation at the Hayashi Eye Hospital between April 24, 2019 and April 20, 2020 were screened for inclusion in the study by ophthalmic technicians. The preoperative exclusion criteria were (1) eyes with pathology of the iris, cornea, retina, or optic nerve; (2) patients with cerebral and psychological disorders; (3) eyes with mydriasis smaller than 4.0 mm; (4) eyes with history of ocular surgery or inflammation; (5) patients with diabetes mellitus; (6) eyes with pseudoexfoliation syndrome; (7) eyes that were enrolled in other studies; (8) patients who did not agree to participate in the study; and (9) patients who had any difficulty undergoing the examinations or 3-month follow-up. The postoperative exclusion criteria were (1) eyes with eventful surgery, (2) eyes that underwent surgical procedures for pupil dilation, and (3) use of pharmacologic agents for pupil dilation or constriction. Only the eye with the better corrected distance visual acuity was included, and the right eye was enrolled in the study when the corrected distance visual acuity was the same in both eyes.
Surgical techniques
All the surgeries were performed by 2 experienced surgeons (K.H., M.Y.) using the previously described surgical procedures [23]. First, 2 side ports were made with a 0.6-mm slit knife at approximately 90° from the main incision. A continuous curvilinear capsulorrhexis measuring approximately 5.0 mm in diameter was created using a bent needle or an anterior capsule forceps. The surgeon then made an approximately 2.4-mm single-plane clear corneal incision or transconjunctival sclerocorneal incision using a steel keratome horizontally for eyes having against-the-rule or oblique corneal astigmatism, and superiorly for eyes having with-the-rule astigmatism. After hydrodissection, the nucleus was phacoemulsified, and the residual cortex, aspirated. The lens capsule was inflated with 1% sodium hyaluronate (Healon, AMO, or Hyaguard, Nitten Co. Ltd), after which the IOL was placed into the capsular bag using a Monarch II injector (Alcon Laboratories). After IOL insertion, the ophthalmic viscoelastic material was thoroughly removed.
Outcome measures
All the patients underwent evaluations of the parameters of the pupillary light response by use of a handheld digital infrared pupillometer (PLR-3000, NeurOptics) before surgery and at 1 day and 1 and 3 months after surgery. The PLR-3000 is a monocular pupillometer that can measure both pupillary constriction by a light stimulus and recovery dilation. This device records the pupillary diameter using an infrared camera (32 frames/sec) and can measure the diameter to within +/- 0.03 mm. The PLR-3000 measures various parameters of the pupillary light response, including maximum (initial) and minimum (end) pupillary diameter (mm), percentage of pupillary constriction (%), latency from a light stimulus to constriction (sec), average constriction velocity (mm/sec), and average dilation velocity (mm/sec). The reproducibility of the PLR-3000 was previously confirmed [24, 25].
Before the measurements were obtained, all the patients were adapted to a bright room with an illuminance level of approximately 200 lux for 5 min. To measure the pupillary constriction parameters, a positive pulse stimulus (10 µW, 0.80 s) was given when patients were looking with a specific eyecup at a steady light placed 5.0 m from the pupillometer. During monocular testing, the patients were instructed to gaze at the steady light with the nonoccluded eye. To measure pupillary dilation parameters, the patients were adapted to a steady light (50 µW, 1.07 s), which was then extinguished for a brief period. Measurements were repeated 3 times with 1-min intervals between each measurement.
The corrected distance visual acuity of the patients was measured on decimal charts, and the decimal visual acuity was converted to the logarithm of the minimal angle of resolution (logMAR) scale for statistical analysis. The refractive spherical and cylindrical powers were measured using an autorefractor/keratometer (KR-7100, Topcon Corporation), and the manifest spherical equivalent value was determined as the spherical power plus half the cylindrical power. Corneal astigmatism was also examined using the KR-7100. Axial length was measured using swept source-optical coherence tomography (IOLMaster 700, version 1.14; Carl Zeiss Meditec). All the examinations were performed by ophthalmic technicians who were not informed of the purpose of the present study.
Statistical analysis
StatView 5.01 software (SAS) was used for the statistical analysis. The normality of the data distribution was evaluated by inspection of the histograms. Because some of the data were not normally distributed, nonparametric tests were used for the analyses. Pupillary diameter, percentage of pupillary constriction, latency to constriction, average constriction velocity, average dilation velocity, manifest spherical equivalent value, corneal astigmatism, corrected distance visual acuity, and other continuous variables were compared using the Kruskal-Wallis test among the 4 time intervals and among the 3 age categories. When a significant difference was detected among the time intervals or age categories, the Mann-Whitney U test was used to compare the data between each pair of time intervals or categories with the Bonferroni adjustment for multiple comparisons. Categorical variables were compared among the 3 age categories by use of the chi-square test or Fisher exact test. Differences with a probability value of less than .05 were considered significant.
Results
All consecutive patients scheduled for hospitalization to undergo phacoemulsification surgery at the Hayashi Eye Hospital between April 24, 2019 and April 20, 2020 (N = 2149) were screened for enrollment in the study. Of the 2149 patients, 477 met the inclusion criteria and were enrolled. Of the 477 enrolled patients, 55 were lost to the 3-month follow-up, leaving 422 eyes of 422 patients for analysis. The numbers of eyes in the 3 age categories were 165 eyes in the patients aged 60 to 69 years, 188 eyes in the patients aged 70 to 79 years, and 69 eyes in the patients aged 80 to 89 years. The mean patient age was 72.1 ± 6.6 years (162 men and 260 women). Comparisons of the preoperative patient characteristics among the age categories are shown in Table 1. The ratio of men to women, ratio of left and right eyes, and corrected distance logMAR visual acuity did not differ significantly among the age categories. The mean manifest spherical equivalent value and corneal astigmatism differed significantly among the age categories (P≤.0069).
Maximum and minimum pupillary diameters
The mean maximum and minimum pupillary diameters differed significantly among the time intervals (P<.0001; Fig. 1). Comparisons between each pair of time intervals revealed that both the maximum and minimum pupillary diameters were significantly smaller at 1 day postoperatively as compared with preoperatively, and at 1 and 3 months postoperatively (P<.0001). Comparisons among the 3 age categories (Table 2) revealed that the mean maximum pupillary diameter was significantly reduced in association with the age category at all time intervals (P≤.0294). The mean minimum pupillary diameter was significantly reduced in association with the age category preoperatively and at 1 day postoperatively (P≤.0142), but it did not differ significantly at 1 and 3 months postoperatively.
Comparison of pupillary constriction and dilation parameters among the time intervals
The mean percentage of pupillary constriction, average and maximum constriction velocities, and average dilation velocity differed significantly among the 4 time intervals (P≤.0002). The mean latency to constriction did not differ significantly among the time intervals. Comparisons between each pair of time intervals revealed that the mean percentage of pupillary constriction was significantly reduced at 1 and 3 months postoperatively as compared with the mean percentage preoperatively and at 1 day postoperatively (P<.0001; Fig. 2). The mean values of the average and maximum pupillary constriction velocities and average dilation velocity were significantly lower at 1 and 3 months postoperatively when compared with the mean values preoperatively and at 1 day postoperatively (P<.0001, Fig. 3).
Comparison of pupillary constriction and dilation parameters among the age categories
The mean percentage of pupillary constriction was significantly reduced in association with the age category at all time intervals (P≤.0100; Fig. 4). The mean latency to constriction differed significantly among the age categories preoperatively and at 1 day postoperatively (P≤.0482) but not at 1 and 3 months postoperatively. The mean values of the average and maximum constriction velocities and average dilation velocity were significantly lower in association with the age category at all time intervals (P≤.0185; Fig. 5).
Pupillary light response of a representative eye preoperatively and at 3 months postoperatively
Figure 6 illustrates the pupillary light response of a representative patient before and at 3 months after cataract surgery. Preoperatively, the percentage of pupillary constriction was 19%. At 3 months postoperatively, the percentage of pupillary constriction was reduced to 10%, and the average constriction and dilation velocities were also decreased.
Discussion
The findings of the present study revealed that both the maximum and minimum pupillary diameters were smaller at 1 day after cataract surgery and recovered to the preoperative level within 3 months of surgery. In contrast, the parameters of the pupillary light response, the percentage of pupillary constriction, and the average constriction and dilation velocities were worse at 1 and 3 months postoperatively as compared with those preoperatively and at 1 day postoperatively. These findings suggest that the pupillary constriction and dilation functions are impaired at several months after cataract surgery.
Whether the pupillary light response worsens with age in healthy eyes that have not undergone cataract surgery remains controversial [16,17,18,19,20,21]. No studies, however, have examined the association between age and the pupillary light response after cataract surgery. In the present study, the pupillary light response was impaired in association with older age before and after cataract surgery. Additionally, the maximum and minimum pupillary diameters were significantly smaller in proportion to age before and after surgery. These findings suggest that the pupillary light response and pupillary diameter were reduced in association with increasing age after cataract surgery.
Although the pupillary diameter and pupillary light response may affect visual function after cataract surgery [8,9,10], few studies to date have examined postoperative pupillary changes. Our previous study showed that the pupillary diameter is reduced immediately after cataract surgery [14], but whether and when the pupillary diameter recovers was unclear. In addition, Peters and Tychsen [15] reported that the pupillary light response does not worsen after planned extracapsular cataract extraction. Komatsu et al. [16] showed that the pupillary constriction and dilation velocity decreased after phacoemulsification, but they examined only 20 eyes. The present study with a large sample size revealed that pupillary size recovers to preoperative levels by 3 months after surgery and that the pupillary light response is impaired at several months after surgery.
The reasons for the impaired pupillary light response after cataract surgery are supposed as follows [26,27,28]. The reduced pupillary diameter immediately after surgery was attributed to the direct mechanical injury of iris tissue and damage through chemical mediators, including substance P. In addition, the impaired pupillary constriction and dilation functions at several months after surgery was attributed to the subsequent atrophy of the pupillary sphincter and dilator muscles. Furthermore, latency to pupillary constriction was not delayed postoperatively, suggesting that the neurologic network underlying the pupillary light response is not markedly worsened. Thus, the functions of the pupillary muscles may be compromised owing to surgical damage associated with cataract surgery.
The present study has several limitations. First, the postoperative follow-up period was only 3 months. The pupillary response parameters apparently worsened for up to 3 months after surgery. Whether these parameters recover to preoperative levels is unclear, but they did tend to improve slightly from 1 to 3 months postoperatively. Further study is necessary to examine the long-term change in the pupillary light response after cataract surgery. Second, dark adaptation before the measurements was not performed. Because light-adapted retinas under photopic conditions are a little less sensitive to light than are dark-adapted retinas, measurements of the pupillary response after dark adaptation is more consistent for comparison between patients. It was practically difficult, however, to perform dark adaptation of longer than 10 minutes in clinical situations [29].
In conclusion, the pupillary light response was impaired several months after cataract surgery and worsened in association with patient age. Reduced pupillary diameter and pupillary light response can cause visual function impairment, including photophobia, photic phenomena, and reduced contrast sensitivity [8,9,10]. Particularly, because the major disadvantages of multifocal IOLs are impaired contrast sensitivity and extensive glare and halo symptoms [30,31,32], such impairment may be enhanced in patients receiving multifocal IOLs [33]. Accordingly, surgeons should examine the pupillary light response in volunteers for multifocal IOLs. When the pupillary light response recovers to the preoperative level, the impaired visual function should also be improved. A follow-up study is underway to examine whether and when the pupillary light response recovers.
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Acknowledgements
The authors thank Koji Yonemoto, PhD (Ryukyu University, Naha, Japan), for statistical assistance.
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Hayashi, K., Yoshida, M., Ishiyama, S. et al. Pupillary light response after cataract surgery in healthy patients. Jpn J Ophthalmol 65, 616–623 (2021). https://doi.org/10.1007/s10384-021-00837-5
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DOI: https://doi.org/10.1007/s10384-021-00837-5