Violet light-transmitting intraocular lens increases choroidal thickness: 1-year prospective, randomised controlled trial

Abstract

Aims

To compare the changes in ocular parameters after implantation of two types of intraocular lenses (IOLs) following cataract surgery. One IOL transmits violet light (VL), and the other does not.

Methods

A total of 402 patients were randomly assigned to receive either a VL-non-transmitting IOL or a VL-transmitting IOL. Ocular parameters were measured preoperatively and postoperatively, and participants completed a lifestyle questionnaire. The choroidal thickness (CT) was measured using the PLEX Elite 9000 (Carl Zeiss Meditec). The associations between changes in CT and age, sex, type of IOL, preoperative CT, time spent outdoors, time spent using a smartphone or tablet and time spent reading were examined using stepwise multiple regression analysis (SPSS V.28.0 for Windows, IBM-SPSS).

Results

The baseline mean spherical equivalents were −4.00±5.97 D and −2.19±4.73 D, the axial lengths were 24.84±1.82 mm and 24.19±1.65 mm, and the CTs were 213.78±102.93 µm and 239.20±104.98 µm for the VL-non-transmitting and VL-transmitting IOL groups, respectively. The mean changes in the CT from 3 to 12 months postoperatively were −0.30±18.32 µm for the VL-non-transmitting IOLs and 3.48±16.46 µm for the VL-transmitting IOLs (p=0.012). Multiple regression analysis identified significant choroidal thickening associated with female sex (p=0.004), VL-transmitting IOL implantation (p=0.049) and increased outdoor exposure (p=0.008).

Conclusion

The choroidal thickening after cataract surgery was associated with the VL-transmitting IOL and longer time spent outdoors with exposure to abundant VL. Despite these findings, this study has several limitations, including a relatively short follow-up period, and it did not assess postoperative lifestyle, VL exposure or actual peripheral defocus in the patients.

Trial registration number

UMIN000038961.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Recent studies have identified time spent outdoors as a protective factor against the development and progression of myopia, and violet light (VL) (360–400 nm), a component of natural sunlight, has also been reported to suppress myopia progression. Furthermore, myopia progression has been associated with choroidal thinning. In the context of an increasingly ageing population, the suppression of choroidal thinning and axial elongation in the demographic undergoing cataract surgery is expected to become an important consideration in future ophthalmic care.

WHAT THIS STUDY ADDS

• This prospective, randomised, controlled trial revealed a statistically significant increase in choroidal thickness from 3 to 12 months postoperatively in eyes implanted with a partially VL-transmitting intraocular lens (IOL) compared with those implanted with a non-VL-transmitting IOL. Multiple regression analysis also showed that choroidal thickening after cataract surgery was associated with the VL-transmitting IOL and longer time spent outdoors, which exposes individuals to abundant VL.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• These findings suggested that both the IOLs that transmit VL and longer time spent outdoors probably caused choroidal thickening, even in elderly individuals who underwent cataract surgery.

Introduction

The prevalence of myopia has been increasing dramatically over the past few decades, and myopia has been identified as a leading cause of visual impairment.^{1 2} The results of a meta-analysis³ found that low, moderate and high myopia were all associated with increased risks of myopic macular degeneration, retinal detachment, cataract and open-angle glaucoma. The prevalence of myopia in adults is also expected to increase in the future because previous studies have reported that its prevalence has been high among children, including preschool children in Tokyo.⁴ Regarding factors associated with myopia suppression, the time spent outdoors has been recognised recently as protective against myopia.5,8

Recently, the choroidal thickness (CT) has attracted attention as a parameter by which myopia progression can be assessed. Some studies have reported the effects of orthokeratology lenses^{9 10} and low-concentration atropine eye drops,^{11 12} which suppress myopia progression in children, by the amount of change in the CT. Compared with the control group, significantly thicker choroids were reported in the orthokeratology lenses group and the low-concentration atropine eye drops group.

Violet light (VL) (360–400 nm wavelength), which is abundant outdoors, has previously been reported to suppress myopia progression. In previous studies, the axial length (AL) was significantly longer in the contact lens (CL) group in which VL was blocked compared with the CL group in which VL was transmitted among junior high school and high school CL wearers.¹³ In adults implanted with an anterior chamber-type phakic intraocular lens (pIOL), the AL over 5 years was previously reported to be significantly longer in the non-VL-transmitting pIOL group than in the VL-transmitting pIOL group.¹⁴

To elucidate the mechanism of VL against myopia progression, genetically engineered animals lacking the VL-sensitive atypical opsin, neuropsin (Opn5) gene specifically in the retina (retina-specific OPN5 conditional knockout mice), were used.¹⁵ The protective effect of VL was shown to require OPN5 in the retina. Changes in the CT were also evaluated in mice with lens-induced myopia using various transmission levels (40%, 70% and 100%) of VL.¹⁶ Choroidal thinning, which is observed in myopic shifts, was suppressed by VL exposure and affected by its transmission. Furthermore, subgroup analysis in a double-masked, randomised, controlled trial showed that the mean changes in AL^{17 18} and CT¹⁸ in the VL-transmitting eyeglasses group were significantly smaller and thicker, respectively, compared with placebo glasses that did not transmit VL.

The implantation of a VL-transmitting IOL during cataract surgery was hypothesised to increase the CT compared with the implantation of a non-VL-transmitting IOL, leading to the design of this prospective, randomised, controlled trial.

Materials and methods

Study design

This is a randomised, single-masked, parallel-group comparative study. The study is registered in the UMIN Clinical Trials Registry (UMIN000038961). All procedures involving human subjects were performed in accordance with the tenets of the Declaration of Helsinki.

A total of 489 patients (489 eyes) who were candidates for cataract surgery were examined at Hayashi Eye Hospital from 11 December 2019 to 9 March 2021. All patients provided written informed consent after they received an explanation of the study. Only the eye first operated on was included in the study. Patients were included whose CT was measurable preoperatively by swept-source optical coherence tomography. Patients were excluded who had ocular diseases other than senile cataract, a history of previous ocular surgery or inflammation, and who were unavailable for follow-up evaluations. The detailed study protocol, including inclusion and exclusion criteria and study procedures, is available online as online supplemental protocol.

On establishing the sample size, based on a previous report of the changes in CT after cataract surgery, the amount of change and SD in the CT were about 20 µm and about 60 µm, respectively.¹⁹ In this study, if the difference between the two groups was estimated to be 20 µm, with a SD of 60 µm, α=0.05 (both sides) and 1−β=0.90, the required number of cases was 190 per group. Considering the dropout associated with the coronavirus 2019 pandemic, the sample size was set at 240 cases per group.

Study intervention

All enrolled patients were randomly assigned on the day before surgery to one of the two IOL groups: the VL-non-transmitting IOL or the VL-transmitting IOL. The postoperative target refraction was determined individually based on each patient’s visual demands and lifestyle preferences. One clerical staff member generated a randomisation code with equal numbers using random number tables, and the patients and examiners were masked to the randomisation. The individual who generated the randomisation code kept the assignment schedule until all data were collected to ensure allocation concealment.

The patients were followed for 1 year postoperatively and the ocular parameters were measured preoperatively and 3, 6, 9 and 12 months postoperatively. The ocular parameters measured were the uncorrected visual acuities, best-corrected VAs, non-cycloplegic objective refraction, corneal refractive power (TONOREF II, Nidek, Tokyo, Japan), AL (IOLMaster 700, Carl Zeiss Meditec, Germany) and subfoveal CT (PLEX Elite 9000, Carl Zeiss Meditec). The CT was measured within approximately 3 hours around 12:00 noon to account for diurnal variation.²⁰ Two independent examiners measured the subfoveal CT and the average values were calculated. The patients also completed the questionnaire preoperatively to record the time spent outdoors, watching TV, using digital devices including computers/smartphones/tablets, reading or studying, reading distance and sleep time.

Patient and public involvement

The patients or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Spectral transmission

The spectral transmission of the IOLs was measured by the ultraviolet (UV)-visible absorption spectra of these samples recorded with a Ultraviolet–Visible–Near Infrared (UV-VIS-NIR) Spectrophotometer SolidSpec-3700i (Shimadzu Corporation, Kyoto, Japan). The VL-transmitting IOL partially transmits VL, which was previously reported to suppress myopia progression,13,1517 18 and the VL-non-transmitting IOL does not transmit VL (figure 1). The peripheral refractions after IOL implantation were simulated, as previously reported.¹⁴ The focusing images of the IOLs on the peripheral retina were calculated using the Liou-Brennan eye model²¹ and ZEMAX optics design software (Radiant Zemax, Redmond, Washington, USA). The obtained paraxial focus position of the IOLs with +20 diopter (D) power was obtained at a wavelength of 440 nm. The retinal spherical surface with a radius of −12.0 mm was set and the defocus amounts for incident angles of 0°, 10°, 20°, 30°, 40° and 45° were calculated at the 4 mm pupillary diameter. Each focus is presented based on the six light rays (online supplemental figure 1).

Figure 1. Spectral transmittance of the violet light (VL)-non-transmitting and VL-transmitting intraocular lenses (IOLs). While the spectral transmittance of the VL-non-transmitting IOL rises steeply from a wavelength of 420 nm, that of the VL-transmitting IOL rises gradually from around 360 nm. Since VL is a visible purple light with a wavelength of 360 to 400 nm (grey area), the VL-transmitting IOL partially transmits VL.

Statistical analysis

The Mann-Whitney U-test was used to compare the differences in the changes in the ocular parameters between the two groups and the sex from 3 to 12 months postoperatively. Because the subfoveal choroid thickens due to inflammation about 3 months after cataract surgery,²² the ocular parameters from 3 months postoperatively were evaluated. The associations between the changes in the CT and other parameters including age, sex (male=1, female=0), IOL type (groups VL-non-transmitting IOL=1, groups VL-transmitting IOL=0), preoperative CT, preoperative spherical equivalent (SE), time spent outdoors, time spent using smartphones or tablets, and time spent reading also were examined by univariate and stepwise multiple regression analysis. The preoperative AL was excluded from the analysis due to its strong correlation with the preoperative SE.

Since a previous report²³ found that a CT of 138.5 µm or less increased the risk of myopic maculopathy regardless of the AL, a group with a CT of 138.5 µm or less at 3 months after cataract surgery was selected, and a subgroup analysis was performed to compare the changes in the parameters between the two IOLs.

All statistical analyses were performed using a statistical analysis software (SPSS for Windows, V.28.0, IBM-SPSS). P<0.05 was considered significant.

Results

The flow of patients in this study is shown in figure 2. Although the protocol targeted 240 patients per group considering potential dropouts due to the COVID-19 pandemic, a total of 489 patients were enrolled. This was due to multiple patients being registered on the same day near the end of the enrolment period. Of these, 84 patients were lost to follow-up, two patients had cystoid macular oedema and one patient had a rhegmatogenous retinal detachment during follow-up, resulting in 402 patients (VL-non-transmitting IOL: 202, VL-transmitting IOL: 200) included in the final analysis. The postoperative exclusion criteria after randomisation were any surgical complication including posterior capsule rupture, asymmetric or out-of-the-bag implantation, any difficulties with the analysis and patient refusal of examination, but no cases met those criteria.

Figure 2. Flow chart of the participants. IOL, intraocular lens; VL, violet light.

The average patient age (±SD) was 68.3±6.8 years (range, 41–79 years; 254 men, 148 women). The patient demographics are shown in table 1. In the VL-non-transmitting IOL and VL-transmitting IOL groups, the mean baseline CTs, SEs and ALs were 213.78/239.20 µm, –4.00/–2.19 D and 24.84/24.19 mm, respectively. Based on the questionnaire, the mean times spent outdoors were 1.99 and 1.98 hours/day, respectively.

Table 1. Characteristics of the participants.

	Total (mean±SD)	VL-non-transmitting IOL (mean±SD)	VL-transmitting IOL (mean±SD)
Patients (n)	402	202	200
Age (years)	68.3±6.8	67.9±6.8	68.6±6.8
Male, %	36.8	40.6	33.0
UCVA, logMAR	−0.89±0.49	−0.93±0.51	−0.86±0.46
BCVA, logMAR	−0.29±0.21	−0.29±0.21	−0.29±0.20
Spherical equivalent (D)	−3.07±5.45	−4.00±5.97	−2.19±4.73
Axial length (mm)	24.52±1.76	24.84±1.82	24.19±1.65
Choroidal thickness (μm)	226.42±104.60	213.78±102.93	239.20±104.98
Time spent outdoors (hours/day)	1.98±1.81	1.99±1.73	1.98±1.89
Time spent watching TV (hours/day)	3.80±2.44	3.81±2.54	3.79±2.35
Time spent using smartphone/tablet (hours/day)	1.20±1.24	1.22±1.23	1.18±1.24
Time spent using computer (hours/day)	1.34±2.21	1.41±2.28	1.27±2.13
Time spent reading/studying (hours/day)	0.87±1.12	0.82±1.06	0.92±1.18
Reading distance (cm)	38.98±6.70	39.59±6.28	38.44±7.03
Sleep time (hours/day)	6.45±1.22	6.48±1.23	6.42±1.18

BCVA, best-corrected visual acuity; D, diopters; IOL, intraocular lens; logMAR, logarithm of the minimum angle of resolution; UCVA, uncorrected visual acuity; VL, violet light.

Table 2 shows that the mean changes in the CT from 3 to 12 months postoperatively were −0.30±18.32 µm for the VL-non-transmitting IOL group and 3.48±16.46 µm for the VL-transmitting IOL group (p=0.012). The SEs were 0.04±0.28 D and 0.04±0.29 D, respectively (p=0.678), and the ALs were 0.00±0.03 mm and 0.00±0.03 mm, respectively (p=0.959). The results of the subgroup analysis, in which the CTs of 138.5 µm or less were selected, are shown in online supplemental eTable 1. Although there were no significant differences in the postoperative changes in the CTs, SEs and ALs between the two IOLs, there was a tendency for the postoperative CTs to increase with the VL-transmitting IOL, which transmits VL, and even in the thin CT group (VL-non-transmitting IOL=0.10 µm, VL-transmitting IOL=4.12 µm, p=0.139).

Table 2. Comparison of ocular parameter changes between the two groups at 3 to 12 months postoperatively.

	Total (mean±SD)	VL-non-transmitting IOL (mean±SD)	VL-transmitting IOL (mean±SD)	P value
Choroidal thickness (μm)	1.58±17.50	−0.30±18.32	3.48±16.46	0.012
Spherical equivalent (D)	0.04±0.28	0.04±0.28	0.04±0.29	0.678
Axial length (mm)	0.00±0.03	0.00±0.03	0.00±0.03	0.959

Bold values indicate statistical significance (P < 0.05).

D, diopters; IOL, intraocular lens; VL, violet light.

Table 3 shows the results of the univariate and multiple regression analyses performed to estimate the association between changes in the CT and other variables with adjustment for confounders including age, sex, baseline CT, IOL type, time spent outdoors, time spent using smartphones or tablets and time spent reading. The results indicated that a thicker choroid after cataract surgery was significantly associated with female sex (coefficient β = −5.305; p=0.004), implantation of the VL-transmitting IOL (β=−3.410; p=0.049) and longer time spent outdoors (β=1.295; p=0.008).

Table 3. Results of simple correlation and multiple regression analysis between changes in CT and variables.

Variable	Univariate analysis (n=367)		Multivariate analysis (n=367)
	Correlation coefficient	P value	Coefficient	P value
Age (years)	0.028	0.296
Sex (male=1, female=0)	−0.135*	0.005	−5.212	0.007
Baseline SE (D)	0.058	0.133
Baseline CT (μm)	−0.027	0.301
Types of IOLs (VL-non-transmitting IOL=1, VL-transmitting IOL=0)	−0.149*	0.002	−4.504	0.013
Time spent outdoors (hours/day)	0.070*	0.090	1.078	0.044
Time spent using smartphone or tablet (hours/day)	−0.044	0.199
Time spent reading (hours/day)	0.006	0.453

Bold values indicate statistical significance (P < 0.05).

^*Significant correlation by the Pearson correlation test.

CT, choroidal thickness; D, diopters; IOL, intraocular lens; SE, spherical equivalent; VL, violet light.

Regarding sex differences in the CT, the mean CT before cataract surgery was 232.0 µm in men and 223.2 µm in women (p=0.49). The mean changes in the CTs after cataract surgery were −1.26 µm in men and 3.23 µm in women from 3 to 12 months postoperatively, with the CT in women significantly thicker (p=0.020).

We simulated the peripheral refraction after IOL implantation and found that there was no difference in the amount of peripheral defocus between the VL-non-transmitting IOL and the VL-transmitting IOL in the eye model simulation (online supplemental figure 1).

Discussion

To the best of our knowledge, this study is the first to prospectively compare the changes in the ocular parameters including the CT after cataract surgery using two types of IOLs with different transmitting wavelengths. The current results showed that the postoperative CT was significantly thicker in women with the VL-transmitting IOL, which partially transmits VL, and in association with longer time spent outdoors.

Because there were differences between the two groups in the baseline SE, AL and CT, a statistical expert was consulted, and age, sex, IOL type, preoperative CT, preoperative SE and lifestyle factors were included in the multivariate analysis. This multivariate analysis of the postoperative CT changes after cataract surgery identified a significant association between the postoperative CT and sex. Several previous studies24,26 have described sex differences in CT, with women having thinner choroids than men, and the results of the present study regarding the differences in the preoperative CT values were similar. The reason for this has been discussed in relation to sex hormones. Previous studies^{24 25} have reported oestrogen receptor mRNA in the human choroid, and an association between oestrogen and the choroid was suggested. In addition to hormonal influences, sex-related lifestyle differences, such as time spent outdoors and duration of near work, may contribute to differences in CT. To the best of our knowledge, no studies have followed changes in the CT in adults. The current study identified a new finding, ie, a significant increase in the CT in women from 3 months to 1 year postoperatively.

Multivariate analysis also showed that the postoperative CT was significantly thicker in the VL-transmitting IOL group, which partially transmits VL. Regarding the two types of IOLs used in this study, the VL-non-transmitting IOL has a hydrophobic acrylic optic with a 6.0 mm optical zone, and the VL-transmitting IOL has an acrylic optic with a 6.0 mm optical zone. The transmitted wavelengths differed significantly between the two IOLs, but there were several other small differences. For example, the refractive indices are 1.47 for the VL-non-transmitting IOL and 1.54 for the VL-transmitting IOL. Refractions in the peripheral retinal area have been considered controversial for myopia progression.^{27 28} Refractions in the peripheral retinal area were simulated in the same eye model (online supplemental figure 1). However, no differences were found in the peripheral defocus between the two IOLs. Although the actual peripheral defocus of the patients was not measured, these simulation results implied that the differences in the changes in the CTs between the two IOLs did not depend on the difference in the peripheral defocus.

Previous studies, including interventional research, have reported that longer outdoor activity time reduces the onset and progression of myopia.⁸ Regarding the relationship between the CT and outdoor activity time, a previous study reported that ocular exposure to mild-intensity or moderate-intensity illumination induced a significant short-term increase in the CT in young adults.²⁹ However, because it has been reported previously that near work decreases the choroidal blood flow³⁰ and reduces the CT,³¹ a multivariate analysis was performed including the time spent outdoors and near work as independent values in the current study. The results suggested that implantation of an IOL with partial transmission of VL and longer time spent outdoors were significant factors in the thickening of the choroid after cataract surgery, indicating that longer time spent outdoors and exposure to VL may have affected the postoperative CT. Although the ALs did not differ significantly between the groups during the 12-month follow-up, the CT is increasingly recognised as a potential early marker of myopic progression. The observed increase in the CT in the VL-transmitting IOL group may represent a protective or adaptive physiologic response that could later translate into meaningful clinical outcomes. In this study, the CT was measured as the total thickness on OCT, and, therefore, the direction of thickening (towards the scleral side or the vitreous side) could not be determined.

Given that changes in CT are thought to occur over a shorter time frame than the changes in the AL, it is possible that AL changes may become apparent with longer-term follow-up. Some studies³² have reported that AL elongation with high myopia continues not only in young adults³³ but also in middle-aged individuals and older adults. For example, Du et al³² reported that the mean AL growth rate was 0.05 mm/year in patients with a mean age of 62.10 years and a mean AL of 29.66 mm. In Japan, Ueda et al³⁴ reported that the age-adjusted frequency of an AL of 26.5 mm or more increased significantly from 2005 to 2017 (3.6%–6.0%; p for trend<0.001), and the age-adjusted prevalence of myopic maculopathy increased significantly with time (1.6% in 2005, 3.0% in 2012 and 3.6% in 2017; p for trend<0.001).³⁵ Individuals in the lowest quartile of CT had a significantly greater OR for the presence of myopic maculopathy than those in the highest quartile of CT after adjusting for confounders, including AL.²³ It was suggested that a long AL and a thin CT are independent risks for myopic macular degeneration. A subgroup analysis of the thin CT group also revealed a trend towards a thicker CT after cataract surgery in the VL-transmitting IOL group. Because of the increasing AL elongation, it may be necessary to review in a future study the wavelength transmission of commercially available IOLs to prevent ocular diseases, including myopic maculopathy.

The study had several limitations. First, the follow-up period was short, ie, 1 year. It may be possible to evaluate the refraction and AL changes with a longer follow-up in aged cataract patients. Second, the actual peripheral defocus of the patients was not measured; however, the simulation results suggested that the differences in the changes in the CTs between the two IOLs did not depend on the differences in the peripheral defocus values. Third, this study did not assess postoperative lifestyle. It is possible that undergoing cataract surgery may have led to changes in lifestyle compared with the preoperative state. However, the postoperative lifestyle was not evaluated using a questionnaire, and accurate quantification of VL exposure was not performed. This remains one of the limitations of the present study.

Despite these limitations, we believe that the results of this study are valid and provide meaningful insights into the relationship between IOL spectral characteristics and postoperative choroidal changes. It is possible that exposure to VL and time spent outdoors contribute to the observed changes in CT through photobiological mechanisms. Further longitudinal studies with longer follow-up and precise quantification of VL exposure are warranted to confirm these findings.

Conclusion

Implantation of a VL-transmitting IOL was associated with a greater postoperative increase in CT compared with a non-VL-transmitting IOL, and the thickening CT after cataract surgery was associated with female sex, implantation of the VL-transmitting IOL and longer time spent outdoors with greater exposure to VL. These findings suggest that the spectral properties of implanted IOLs may influence the choroidal response following cataract surgery.

Data availability statement

Data are available on reasonable request.