Over the recent years, patient expectations regarding the outcome of cataract surgery have increased.1–4 Regardless of the type of intraocular lens (IOL) implanted, simple removal of the opaque lens and the correction of blurred vision no longer satisfy patients; they also expect accuracy in postoperative refraction.1 However, patients with monofocal IOLs may find it acceptable to wear glasses, at least on some occasions. Multifocal IOLs are currently more commonly used, largely because they are more likely to allow a spectacle-free life after cataract surgery.5,6 Considering patients’ expectations of a spectacle-free life, those who receive multifocal IOLs are less tolerant of postoperative refractive errors. In fact, some studies have reported that for multifocal IOL implantation, postoperative refractive error is one of the main causes of patient dissatisfaction.7 In extreme situations, some patients with refractive error may require IOL explantation.8,9 From a doctor's point of view, it is unrealistic to expect an outcome without any margin of error in terms of postoperative refraction; therefore, it is necessary for the clinician to candidly communicate the characteristics of multifocal lenses to the patient before surgery, including the margin of error of postoperative refraction.
Mydriatic eye drops stimulate sympathetic nerves and cause relaxation and contraction of the ciliary and dilator muscles, respectively. Consequently, lens thickness (LT) is reduced, and the anterior chamber depth (ACD) is increased. Therefore, pupil dilation may influence IOL power calculation formulas, such as calculation of predicted postoperative refraction (PPR) and recommended IOL power.
Although third-generation formulas, such as the SRK/T and Hoffer Q formulas, do not include ACD and LT as biometric measurements,10,11 fourth-generation formulas, such as the Haigis and Holladay 2 formulas, do.12–14 In our previous study, we demonstrated that in monofocal IOLs, pupil dilation does not influence third-generation formulas, but does influence fourth-generation formulas.15
In addition, given that monofocal and multifocal IOLs have different optical designs and light distributions,16 the effect of pupil dilation on PPR and recommended IOL power calculated using third- and fourth-generation formulas may differ between monofocal and multifocal IOLs. However, previous studies conducted on this topic have focused on monofocal IOLs. In the published studies, the influence of pupil dilation on IOL calculation formulas for monofocal IOLs has been reported.17–19 Our previous work was the first study that investigated the correlation between PPR, ACD, and LT in both third- and fourth-generation IOL calculation formulas for monofocal IOLs.15 The scope of the current study is to compare monofocal and multifocal IOLs, as influenced by the effect of pupil dilation on PPR and recommended power, and to analyze the correlation between PPR, ACD, and LT.
At our institute, we used either SN60WF monofocal IOLs (Alcon Laboratories, Inc., Fort Worth, TX) or +3.25 D (ZLB00) TECNIS MF 1-piece diffractive multifocal IOLs (Abbott Medical Optics, Inc., Santa Ana, CA). This was a retrospective study that featured 280 eyes (162 SN60WF and 118 ZLB00) of 150 patients (87 with SN60WF monofocal IOLs, and 63 with ZLB multifocal IOLs) with cataracts, who underwent uneventful phacoemulsification with IOL implantation at the XXX Eye Clinic or the XXX Clinic in Japan.
Ethics committees of both participating institutions approved this research. After receiving a thorough explanation, patients signed consent forms allowing the use of their medical records for research. Data collection adhered to the tenets of the Declaration of Helsinki.
Only good-quality data, obtained by the IOL Master 700 (Carl Zeiss Meditec AG, Jena, Germany), were used. Patients with best-corrected visual acuity better than 20/40 postoperatively, and without a history of previous eye operations were included. Patients with cataracts that were not age-related and those with surgical complications were excluded.
ACD and LT were measured preoperatively with the IOL Master 700 and the recommended IOL power for both SN60WF and ZLB00 IOLs were calculated using third-generation and fourth-generation formulas. We used constants of 119.0 and 119.3 for the SN60WF and ZLB00, respectively, which were proposed by the User Group for Laser Interference Biometry.20 After the first examination, topical tropicamide and phenylephrine (Midrin-P, Santen, Osaka, Japan) were given every 15 minutes, and a second examination was performed in the same manner, once complete pupil dilation was achieved.
The mean change in ACD and LT and the mean absolute change (MAC) in PPR, for both IOLs, calculated using both formulas, between before and after dilation, were compared. Additionally, the correlation of the changes in ACD and LT with the change in PPR was analyzed for each IOL. Furthermore, the correspondence of the recommended IOL power calculated before and after dilation, was investigated. Based on these results, for both types of IOLs, the influence of pupil dilation on various IOL calculations based on the third- and fourth-generation formulas were compared.
We assessed the normality of data distribution for each continuous variable, ACD, LT, and PPR, with the Kolmogorov–Smirnov test; all of these variables showed a nonparametric distribution. Changes in biometric variables between before and after pupil dilation were performed using the Wilcoxon signed-rank test. The correlation between biometric variables was investigated using Spearman rank-order correlation test. Recommended IOL power values differing within ± 0.5 D were regarded as coinciding. To compare recommended IOL power values, Fisher exact test was used. In this study, statistical significance was assumed for P < 0.05 (2-sided P values). We used the Bell Curve for Excel version 1.03 (Social Survey Research Information Co., Ltd., Tokyo, Japan) to analyze all statistical data.
The required sample size for the primary analyses was calculated using G-power version 3.1.7 (University of Kiel, Germany), with an anticipated effect size of 0.5 (moderate), a significance level of α = 0.05, and an expected power of 0.8. This calculation suggested that a sample size of at least 67 was required per group.
The clinical characteristics of the 150 patients involved in this study (monofocal: 87; multifocal: 63) are as follows. Mean patient age was 72.9 ± 7.7 years (range: 51–87 years) in the monofocal group and 70.8 ± 7.2 years (range: 49–82 years) in the multifocal group. Males comprised 39.6% and 42.9% of patients in the monofocal and multifocal groups, respectively. For the 280 eyes assessed, the mean preoperative ACD was 3.09 ± 0.43 mm (range: 2.01–4.90 mm) for monofocal and 3.05 ± 0.38 mm (range: 2.23–4.28 mm) for multifocal IOLs, whereas LT was 4.61 ± 0.45 mm (range: 3.44–6.28 mm) for monofocal and 4.63 ± 0.46 mm (range: 3.47–5.88 mm) for multifocal IOLs, respectively.
Table 1 shows the effect of pupil dilation on ACD and LT. Pupil dilation caused a significant effect on ACD and LT, for both IOLs (both P < 0.0001). The ACD significantly increased after pupil dilation, whereas LT significantly decreased. When the 2 groups were assessed irrespective of the IOL type inserted, the results followed the same pattern, with ACD significantly increased while LT decreased (both P < 0.0001).
For both IOLs, the MAC of PPR, between pre- and post-pupil dilation among the 4 formulas, was analyzed (Table 2). Data showed that the values obtained using the Haigis (0.039 ± 0.026 for monofocal and 0.045 ± 0.027 for multifocal IOLs) and Holladay 2 (0.038 ± 0.023 for monofocal and 0.044 ± 0.024 for multifocal IOLs) formulas were significantly higher than those determined using the Hoffer Q (0.007 ± 0.007 for monofocal and 0.008 ± 0.007 for multifocal IOLs) and SRK/T (0.005 ± 0.006 for monofocal and 0.005 ± 0.006 for multifocal IOLs) formulas (all P < 0.0001). Additionally, using fourth-generation formulas, the change in PPR for multifocal IOLs was significantly higher than that for monofocal IOLs (P = 0.009), but this relationship was not evident while using third-generation formulas (P = 0.969).
For both IOLs, changes in pre- and post-dilation PPR showed a significantly positive correlation with changes in pre- and post-dilation ACD, for both the Haigis (Spearman rho = 0.95, P
< 0.0001 for monofocal IOLs; Spearman rho = 0.94, P
< 0.0001 for multifocal IOLs) and Holladay 2 (Spearman rho = 0.95, P
< 0.0001 for monofocal IOLs; Spearman rho = 0.93, P
< 0.0001 for multifocal IOLs) formulas. However, this was not observed while using the Hoffer Q (Spearman rho = −0.0084 for monofocal IOLs; Spearman rho = 0.197 for multifocal IOLs) and SRK/T (Spearman rho = −0.016 for monofocal IOLs; Spearman rho = 0.103 for multifocal IOLs) formulas (Fig. 1). However, for both IOLs, changes in pre- and post-dilation PPR demonstrated a significantly negative correlation with changes in LT, based on both the Haigis (Spearman rho = −0.45, P < 0.0001 for monofocal IOLs; Spearman rho = −0.89, P < 0.0001for multifocal IOLs) and Holladay 2 (Spearman rho = −0.42, P < 0.0001 for monofocal IOLs; Spearman rho = −0.86, P < 0.0001 for multifocal IOLs) formulas. This strong correlation was not evident while using the Hoffer Q (Spearman rho = −0.096 for monofocal IOLs; Spearman rho = −0.191 for multifocal IOLs) and SRK/T (Spearman rho = −0.008 for monofocal IOLs; Spearman rho = −0.075 for multifocal IOLs) formulas (Fig. 2). Interestingly, while using the fourth-generation formula, the correlation between the change in PPR and the change in LT was significantly stronger for multifocal IOLs than that for monofocal IOLs (P < 0.0001). No such relationship was evident between changes in PPR and ACD. Regarding the relationship between age and the influence of pupil dilation on ACD and LT, the younger the subjects were, the more significantly the ACD and LT changed (Fig. 3). In other words, as age increased, the influence of pupil dilation on the ACD and LT significantly decreased (P < 0.0001).
Table 3 shows the relationships between recommended IOL power when pre- and post-pupil dilation were calculated by third- and fourth-generation formulas, for both multifocal and monofocal IOLs. Recommended IOL power, as calculated by fourth-generation formulas, changed between pre- and post-dilation in 15.4% of monofocal IOLs and in 18.6% of multifocal IOLs, respectively, whereas third-generation Hoffer Q and SRK/T calculations showed very few or no changes for either type of IOLs (1% in monofocal IOLs and 0.0% in multifocal IOLs). The discrepancy rate in terms of recommended IOL power between pre- and post-pupil dilation, as calculated by fourth-generation formulas, was significantly higher than those calculated by third-generation formulas, for both types of IOLs (P < 0.0001).
In this study, we investigated the effect of pupil dilation on PPR and IOL power values, as calculated by third- and fourth-generation formulas. We demonstrated that PPR calculated by fourth-generation formulas for multifocal IOLs may be more sensitive to pupil dilation than that of monofocal IOLs. To the best of our knowledge, this is the first study to have done so.
Although multifocal IOLs led to a higher rate of spectacle independence21 and patient satisfaction,22 even minor refractive error can cause blurred vision, which may lead to patient dissatisfaction. Alfonso et al demonstrated that if the mean refractive error was 0.200 ± 0.490 D for distant vision, the patients required laser-based vision correction following multifocal lens implantation.23 In another article, Muftuoglu et al reported that mean refractive errors of −0.34 ± 0.90 required additional vision correction after cataract surgery and implantation of multifocal IOLs. The degree of postoperative refractive error can be regarded as negligible for cataract surgery involving monofocal IOLs. However, these studies demonstrated that doctors need to consider the margins of error for the implantation of multifocal IOLs in particular.
Furthermore, previous studies have demonstrated that one of the major causes of IOL explantation or exchange for multifocal IOLs, is incorrect power calculation.9,24 Therefore, we considered that it is crucial to investigate the influence of pupil dilation on postoperative refraction in cases treated with multifocal IOLs.
Pupil dilation is imperative for preoperative ophthalmic examination. It is also important to select suitable IOL calculation formulas to improve the accuracy of IOL calculations.
Khambhiphant et al17 demonstrated that ACD was significantly affected by pupil dilation. This trend was also reported by other studies.25–27 Our previous research has also shown that not only ACD but also LT was significantly influenced by pupil dilation.15
In this article, we focused on the potential influence of pupil dilation on IOL calculations based on different formulas. Adler et al18 and Khambhiphant et al17 showed that when calculated using the SRK/T formula, PPR did not change significantly after pupil dilation. Furthermore, when the Haigis formula was used to calculate PPR and recommended IOL power, there was a clear and significant change after pupil dilation.19 However, the majority of published literature has investigated the influence of pupil dilation using third-generation IOL calculation formulas, and the amount of literature that used fourth-generation IOL calculation formulas is limited. Additionally, all published article, including our previous study that dealt with this topic, used monofocal IOLs. Therefore, the comparison of influence of pupil dilation between monofocal and multifocal IOLs using third- and fourth-generation IOL calculation formulas was worth researching.
It is evident that the influence of pupil dilation on PPR may vary according to the formula used, as different formulas include different variables. Therefore, it is vital to be familiar with the composition of third- and fourth-generation IOL calculation formulas to consider the influence of pupil dilation on PPR and recommended IOL power for both multifocal and monofocal IOLs. The SRK/T and Hoffer Q calculations were originally based on the Fyodorov's formula.28 Retzlaff et al formulated the SRK/T in 1990,10 while the Hoffer Q was formulated in 1993.11 Both of these formulas include corneal curvature radius and axial length (AL) to determine the estimated lens position (ELP), but do not include ACD and LT. The difference between these two formulas is that the Pythagorean theorem is used to calculate ELP in the SRK/T formula, while the trigonometric function is used in the Hoffer Q formula.
With regards to fourth-generation formulas, the Holladay 2 was first introduced in 199612 and included AL, corneal curvature radius, transverse corneal diameter, age, sex, and ACD to estimate ELP. In contrast, the Haigis formula, which was first published in 2004,13 uses ACD and AL, along with a regression equation, to predict ACD. Therefore, the major difference in components between third- and fourth-generation formulas is that ACD is included in the fourth-generation formulas. It is thus plausible that PPR and recommended IOL power are affected by pupil dilation in fourth-generation formulas, but not in third-generation formulas. However, to the best of our knowledge, no previous study has investigated the relationship between LT and IOL calculation formulas.
A previous study demonstrated that although pupil dilation did not affect PPR and the recommended IOL power when calculated using third-generation formulas, it did affect these variables when calculated by fourth-generation formulas.15 In contrast to the present study, our previous study only dealt with monofocal IOLs. In addition, this study indicated that changes in ACD and LT played important roles in the effect of pupil dilation on fourth-generation IOL calculation formulas. Nevertheless, this and other studies were conducted only for monofocal IOLs. Considering the differences in optical design and light distribution between monofocal and multifocal IOLs,8 it was deemed necessary to compare the influence of pupil dilation on PPR and recommended IOL power between the 2 types of IOL.
In our current research, multifocal IOLs showed similarities and differences in outcomes to monofocal IOLs, for both third- and fourth-generation IOL calculation formulas. For both types of IOL, the MAC in PPR between pre- and post-pupil dilation, while using the fourth-generation formulas, was significantly greater than when using third-generation formulas. In addition, for each IOL, the change in PPR while using fourth-generation formulas showed a statistically significant positive correlation with changes in ACD, and a statistically significant negative correlation with changes in LT. However, these relationships were not evident for values calculated using third-generation formulas, for both types of IOL. Furthermore, for both types of IOL, the recommended IOL power was also affected by pupil dilation when using fourth-generation, but not when using third-generation formulas. These results indicate that for both IOL types, the change in ACD and LT between pre- and post-pupil dilation may play a vital role in the improvement of IOL calculations.
Although the outcomes of multifocal and monofocal IOLs share some common features, there were also differences that cannot be neglected when attempting to improve the predictive accuracy of postoperative refraction. First, for multifocal IOLs, the MAC in PPR between pre- and post-pupil dilation was significantly larger than that for monofocal ones. Second, for multifocal IOLs, the correlation between LT change and PPR change was significantly larger than that for monofocals. However, this relationship was not evident in the correlation between ACD change and PPR change. Finally, the recommended IOL power for multifocal IOLs changed more frequently than that for monofocals, although this was not statistically significant. This may indicate that for multifocal IOLs, pupil dilation is more likely to affect the doctor's selection of IOL.
Despite reaching novel findings and being the first study to assess the effect of PPR on IOL power calculation based on 2 different formulas, this study also has limitations to list. First, we investigated only 1 brand of multifocal IOL. Currently, various types of multifocal IOLs are commercially available and have different types of optical design and light distribution. It is therefore possible that different types of multifocal IOLs may yield different results from those described in this study. Moreover, we focused on a single population, and the results of the study cannot be generalized to other populations. Additionally, the study did not include strict causality. Furthermore, we did not investigate the effect of pupil dilation on predicative error in refraction. This limitation should be addressed in further studies, in which the constant for measurement is optimized with or without pupil dilation; this will help improve the accuracy of PPR.
In conclusion, the results of this study demonstrate that the prediction of postoperative refraction for multifocal IOLs may be more vulnerable to pupil dilation when using fourth-generation formulas. As even minor postrefractive error can cause patient dissatisfaction, with regards to the outcome of multifocal IOL implantation, gaining in-depth knowledge of the effect of pupil dilation on fourth-generation calculations for multifocal IOLs is imperative to improve the accuracy of IOL calculation.
The authors thank Editage (www.editage.com) for English language editing.
1. Mollazadegan Z, Lundström K. A study of the correlation between patient-reported outcomes and clinical outcomes after cataract surgery in ophthalmic clinics. Acta Ophthalmol
2. Chen Z, Lin X, Qu B, et al. Preoperative expectations and postoperative outcomes of visual functioning among cataract patients in Urban Southern China. PLoS One
3. Tielsch JM, Steinberg EP, Cassard SD. Preoperative functional expectations and postoperative outcomes among patients undergoing first eye cataract surgery. Arch Ophthalmol
4. Goodman G, Stark WJ, Gottsch JD, et al. Visual disabilities related to intraocular lens design. Yan Ke Xue Bao
5. Alio JL, Abdelghany AA, Fernández-Buenaga R. Enhancements after cataract surgery. Curr Opin Ophthalmol
6. Medical Advisory SecretariatIntraocular lenses for the treatment of age-related cataracts: an evidence-based analysis. Ont Health Technol Assess Ser
7. Gibbons A, Ali T, Waren DP, et al. Causes and correction of dissatisfaction after implantation of presbyopia-correcting intraocular lenses. Clin Ophthalmol
8. Gundersen KG, Makari S, Ostenstad S, et al. Retreatments after multifocal intraocular lens implantation: an analysis. Clin Ophthalmol
9. Veselá M, Baráková D, Lenčová A. Analysis of reasons of intraocular lenses explantation. Cesk Slov Oftalmol
10. Retzlaff JA, Sanders DR, Kraff MC. Development of the SRK/T intraocular lens implant power calculation formula. J Cataract Refract Surg
11. Hoffer KJ, Kenneth J. The Hoffer Q formula: a comparison of theoretic and regression formulas. J Cataract Refract Surg
12. Holladay JT. Holladay IOL Consultant Computer Program. Houston, TX:Holladay IOL Consultant; 1996.
13. Haigis W. The Haigis formula. In: Shammas H, editor. Intraocular Lens Power Calculations. Thorofare, NJ: Slack; 2004. 41–57.
14. Hoffer KJ. Clinical results using the Holladay 2 intraocular lens power formula. J Cataract Refract Surg
15. Teshigawara T, Meguro A, Mizuki N. Influence of pupil dilation on predicted postoperative refraction and recommended IOL to obtain target postoperative refraction calculated by using third- and fourth-generation calculation formulas. Clin Ophthalmol
16. Salerno LC, Tiveron MC Jr, Alió JL. Multifocal intraocular lenses: types, outcomes, complications and how to solve them. Taiwan J Ophthalmol
17. Khambhiphant B, Chatbunchachai N, Pongpirul K. The effect of pupillary dilatation on IOL power measurements by using the IOL-Master. Int Ophthalmol
18. Adler G, Shahar J, Kesner R, et al. Effect of pupil size on biometry measurements using the IOLMaster. Am J Ophthalmol
19. Rodriguez-Raton A, Jimenez-Alvarez M, Arteche-Limousin L, et al. Effect of pupil dilation on biometry measurements with partial coherence interferometry and its effect on IOL power formula calculation. Eur J Ophthalmol
20. User Group for Laser Interference Biometry. Optimized IOL constants for the ZEISS IOLMaster. Ocusoft.de. Available at: http://ocusoft.de/ulib/c1.htm
. Published 2016. Accessed May 8, 2020.
21. Cochener B, Lafuma A, Khoshnood B, et al. Comparison of outcomes with multifocal intraocular lenses: a meta-analysis. Clin Ophthalmol
22. Multifocal IOL Implants. American Academy of Ophthalmology. Available at: https://www.aao.org/bcscsnippetdetail.aspx?id=6dcd4ff7-2cda-4f63-868e-9120b17caab3
. Accessed January 20, 2019.
23. Alfonso JF, Fernández-Vega L, Montés-Micó R, et al. Femtosecond laser for residual refractive error correction after refractive lens exchange with multifocal intraocular lens implantation. Am J Ophthalmol
24. Kamiya K, Hayashi K, Shimizu K, et al. Survey Working Group of the Japanese Society of Cataract and Refractive Surgery. Multifocal intraocular lens explantation: a case series of 50 eyes. Am J Ophthalmol
25. Huang J, McAlinden C, Su B, et al. The effect of cycloplegia on the lenstar and the IOLMaster biometry. Optom Vis Sci
26. Sheng H, Bottjer CA, Bullimore MA. Cycloplegia had no significant effect on IOLMaster axial length measurements. Optom Vis Sci
27. Arriola-Villalobos P, Díaz-Valle D, Garzòn N, et al. Effect of pharmacologic pupil dilation on OLCR optical biometry measurements for IOL predictions. Eur J Ophthalmol
28. Fedorov SN, Kolinko AI, Kolinko AI. Estimation of optical power of the intraocular lens. Vestn Oftalmol
1967; 80:27–31. [In Russian].