In the last two decades, the PIOL research has gone through several stages, evolving from a small number of studies to a widely discussed topic. A total of 65 countries have participated in PIOL research, among which Spain was the earliest contributor and has made notable contributions. Other countries with major contributions to the field include the United States, China, Germany, and Japan. Collaborations between various countries are very close, particularly among countries with major contributions. We found that the institutions with the most publications are almost all universities in various countries, which clearly shows that the development of clinical research is inseparable from both the general support of universities and the close relationships between ophthalmology departments and major universities. In addition, we find that the authors who started earlier in this field tend to produce more articles and do more in-depth research, which may be related to their long-term accumulated resources and high-level teams. In addition, we find that the journals that publish PIOL-related articles focus on the field of ophthalmology and rarely in comprehensive journals, which may be related to the professional specialization of PIOLs.
The accumulation of early experience was the key to the successful clinical application of PIOLs at the beginning of this century. As early as 1987, a clinical trial reported the clinical application of multifocal IOLs. This study included 46 eyes in 38 patients and evaluated postoperative distant and near visual acuity21. However, limited by imperfect IOL power calculations and manufacturing process of IOLs, as well as the high price and other factors, in the following extended period of time, related research was infrequent, and the number of published studies was also very small. We noticed that in the years before 2000, there were several events that played a major role in promoting the application of PIOLs: the emergence of the IOL Master (Carl Zeiss Meditec), strongly impacting eye biometrics22; the launch of commercial multifocal IOLs by several IOL manufacturers, after which the popularity of multifocal IOLs gradually increased; and the development of more accurate fourth-generation IOL power calculation formulas such as the Holladay 2 and Haigis formulas22, 23. By 2000, many different forms of multifocal IOL appeared in various reports24, 25, 26.
In the initial stage (from 2000 to 2006), the overall volume of publications was still small and included only animal experiments and early clinical observation studies. During this period, there were few types of multifocal IOL available on the market, and there were no products combined with toric IOLs. The field was still in an exploratory stage, with little confidence in clinical applications. In an animal experiment, Boothe et al. found a method that may be more effective in treating on congenital cataracts by implanting multifocal IOLs combined with extended-wear contact lenses into rhesus monkeys’ eyes27. Although they are difficult to access and expensive to use in experiments, rhesus monkeys, the primate closest to humans, are the best available animal model. The success of animal experiments has given clinicians enough confidence that some clinical trials are gradually being carried out, with many in Spain. In a randomized, double-masked clinical trial published in Ophthalmology in 2000, Javitt et al. found that patients with multifocal IOL implantation had less dependence on glasses and better overall vision than those with monofocal IOL but experienced more visual disturbances, such as glare or halo28. In addition to studies of efficacy, we find that there is considerable interest in the side effects of MfIOL: the two most cited articles are about dissatisfaction with multifocal IOLs, but they conclude that most postoperative dissatisfaction can be avoided through effective treatment measures taken in most cases29, 30. Also, Montés-Micó R et al. reported that the contrast sensitivity performance of multifocal IOL was not as good as that of monofocal IOL at near distances and suggested that patients should be carefully selected when choosing multifocal IOL, a concept that continues to this day31, 32.
On the other hand, there is also active research on toric IOLs, which can correct corneal residual astigmatism after cataract surgery. It is estimated that nearly half of cataract patients have corneal astigmatisms greater than 1 diopter (D), which may significantly affect visual acuity (VA) after surgery33, 34, 35, 36. The countries leading early progress in this field were Germany, the United States, and the Netherlands, and included iris fixation37, Z-haptic 38, and plate-haptic IOLs39. The biggest problem toric IOL faces is that, unlike glasses, it may rotate in the eye, resulting in a decline in its ability to correct astigmatism. Ruhswurm et al. conducted a long-term follow-up study of 37 eyes (30 patients) implanted with single-piece plate-haptic silicone IOLs from 1993 to 1998, and confirmed that this type of toric IOL has reliable long-term effects and good rotational stability40. Subsequently, Till et al. found that toric IOL implantation could help some patients correct astigmatism and reduce their dependence on glasses in a retrospective study involving 81 patients41. In addition, they found that IOL rotation most commonly occurred 1 week after surgery. Although some scholars have proposed that limbal relaxing incisions (LRIs) can be used to correct corneal astigmatism, it is generally believed that toric IOLs have more stability and accuracy42, 43. There is no unified standard for LRI and there are great differences among physicians due to manipulation.
The decade from 2007 to 2016 is the golden period for the development of PIOL; the overall volume of papers has increased steadily, more countries/regions have participated in this field, and a variety of previously proposed concepts have been implemented and applied in the clinic at this stage. The publication of several studies on the clinical application of trifocal IOLs verified the conjecture made by Pedro et al. in 200544. In 2011, Gatine et al. used relevant software to design and verify the theoretical feasibility and effectiveness of the precise combination of two kinds of diffractive profiles to obtain diffractive trifocal IOLs, laying the theoretical foundation for three-focus design45. Damien et al. used an optical bench to measure modulation transfer functions to compare 9 kinds of IOLs, including bifocal and trifocal IOLs, and found that trifocal IOLs had more advantages to performance at intermediate distances 46. During this period, there were also a variety of trifocal IOL clinical observations and research studies. A retrospective study by Sheppard et al. in 2013 found that trifocal IOLs implanted bilaterally could obtain better overall vision. This study was an early clinical study of trifocal IOLs, including only a small number of cases (30 eyes from 15 patients) 47. Good performance of trifocal IOLs was also demonstrated by a study by Mojzis et al. to correct presbyopia by implanting a trifocal IOL into 60 eyes of 30 patients48. Notably, as early as 2014, this team proposed the concept of refractive lens exchange. In addition to various objective indicators, some studies have focused on questionnaires that reflect the subjective feelings of patients, including the Catquest-9SF49, VFQ-2550, and Near Activity Visual questionnaire51.
There is a significant connection point between the toric and multifocal IOL studies. In the cluster analysis, we found that this connecting node was an article titled: Effect of astigmatism on visual acuity in eyes with a diffractive multifocal intraocular lens. This article showed that among patients with a bifocal IOLs, those with 1.50 D and 2.00 D astigmatism had worse postoperative visual acuity at all distances than those with astigmatisms of 0.00 D and 0.50 D suggesting the need to reduce corneal astigmatism below 1.00 D when implanting a multifocal IOL. Large preoperative corneal astigmatism often limits the application of multifocal IOLs, which results in poor visual acuity at all distances postoperatively52. Broadening the types of multifocal IOLs, multifocal IOLs with toric designs have been available since 200753. A retrospective study by Peter et al. included 64 eyes of 35 patients implanted with a bifocal toric IOL model AT LISA 909M, which found that a main incision of less than 2.2 mm is preferable for PIOLs54. In addition, a cohort study by Nienke et al55 and a prospective case series study by Alió et al56 also confirmed the advantages of toric multifocal IOL.
In addition to multifocal IOL, EDoF IOL has been widely used in clinic in recent years. EDoF technology is dedicated to expanding the depth of focus. When the distance between the focal points is within a certain range, the focal points can be seamlessly connected to form a continuous visual field. The principles of EDoF IOLs include diffraction, wavefront aberration, and small-aperture imaging. The advantages of EDoF IOL compared with conventional multifocal IOL are less visual interference and higher tolerance for refractive error57. The EDoF IOL performs better than other multifocal IOLs when IOL power calculation is difficult, with sufficient confidence, such as when calculating IOL power in post refractive patients58. Ben et al. used an optical bench based on the Lobb eye model to compare EDoF IOLs with conventional bifocal IOLs (AcrySof ReSTOR SA60D3, Alcon Laboratories Inc.) and found that EDOFs main advantage was increased tolerance to decentration and astigmatism59. In a retrospective study by Torun-Acar et al., patients implanted with a trifocal IOL combined with EDoF technology were found to have high satisfaction, good contrast sensitivity, and significant improvement in overall vison56. However, due to the limited use of EDoF IOLs at the time of publication, the number of cases included in this study was relatively small (80 eyes of 40 patients). In contrast, Cochener et al. included a total of 822 eyes (411 patients) implanted with EDoF IOLs in a larger multicenter study in 2016 and reached the same conclusions as Torun-Acar 60. EDoF IOLs have become an emerging focus in the development of PIOLs due to their excellent design principles, coherent focus switching, higher accommodation of refractive errors, and comparatively less visual disturbance.
In addition to the innovation and development of IOL materials, PIOL applications expanded from routine cataract patients to special cases at this stage. Relevant keywords from the top 30 keywords included photo refractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK). Both PRK and LASIK are common refractive surgeries, and most patients who undergo surgery hope to no longer need glasses afterwards. Due to their altered corneal morphology and the deviation from the normal range of the eye axis, patients have a greater chance of deviations in the IOL power calculation and often have difficulty taking advantage of PIOLs after surgery61. Khoramnia et al. reported a case of a patient who had undergone multiple refractive surgeries and achieved better distance and near visual acuity after the implantation of a PIOL, showing that PIOLs could provide relatively accurate results even in challenging cases62. Similarly, a clinical trial by Freitas et al. confirmed the feasibility of multifocal IOLs in post refractive surgery patients63. Additionally, refractive surgery may help patients with an implanted PIOL to correct residual refractive error from surgery and improve postoperative outcomes64. Although the proportion is currently small, with the increasing age of those who have undergone refractive surgery, we believe that there will be many patients who can benefit from a second refractive surgery in the future, and research into this application is currently lacking.
In the six years from 2017 to 2022, the number of articles on PIOL increased sharply and shifted from predominantly theoretical research to mainly clinical studies. This is also related to the price reduction of a variety of PIOLs and the trend of world economic development. In the previous stage, we found that except for China, which ranked eighth, the top ten countries with published articles were developed countries with well-established health care systems. At this stage, not only had the number of articles published by China increased significantly and risen to second place, but India and Turkey were also among the top ten countries. The large number of patients with cataracts in developing countries will be a potentially expansive market for PIOLs. In addition, some of the latest generations of artificial intelligence-based IOL power calculation formulas (including the Kane formula, Hill-radial basis function formula (Hill-RBF), and PEARL-DGS formula) need to obtain a large amount of local patient data to optimize training and computation accuracy. Therefore, we expect the proportion of articles from developing countries to continue to increase65.
Another noteworthy trend is the increase in the proportion of toric IOL research. Through keyword analysis in this period, we found that the related keywords, “astigmatism” and “toric intraocular lens,” were the first and third most common, respectively. Their frequency even exceeds that of multifocal IOL. We speculate that this may be related to the widespread use of PIOLs and the importance clinicians attach to the correction of astigmatism, and PIOLs are no longer contraindicated for many patients with high astigmatism and even some patients with irregular astigmatism7, 66, 67. Because nearly half of patients requiring cataract surgery have corneal astigmatism that needs to be corrected, multifocal IOLs combined with toric function are widely used. A multicenter prospective clinical trial included 227 eyes of 114 patients with trifocal toric IOL implantation, and after a 12-month observation found that the patient satisfaction reached 98.1%, which reflected good overall visual acuity while correcting astigmatism. At the same time, they also reported that halos, the main photic phenomena, are unavoidable in this kind of IOL68. Similarly, the research of Rementeria-Capelo et al. also showed that the performance of trifocal toric IOLs is almost the same as that of nontoric versions on the same platform69. In addition, a study by Paul et al. found that trifocal toric IOLs were also deemed highly satisfactory by people who received refractive lens exchange, but this study also found a high proportion of patients experiencing postoperative halo70.
We have seen a steady increase in the number of publications and keyword highlights for EDoF IOL in recent years. Clinical application of EDoF IOLs may also increase because it can provide continuous vision over a range of distances, is closer to human eye perception, and has fewer visual disturbances. A retrospective comparative study by Zhu et al. found that EDoF IOLs had the best quality of vision and the least photic disturbance compared to non-EDoF MfIOL; however, near VA was worse than that of conventional types71. Similarly, Karuppiah et al. found that the EDoF group had better contrast sensitivity than the trifocal non-EDoF IOL group. However, the current EDoF IOL also has the significant disadvantage of insufficient near vision, which may require glasses for viewing near object72. An improvement in near vision has been reported for a newer model of EDoF IOL TECNIS Synergy (model ZFR00V); however, this IOL is not yet available in several countries and regions, and supporting studies are still scarce, although we expect more relevant studies to emerge73, 74, 75. We believe that a satisfactory IOL should include the following features: good contrast, overall vision, and as few photic disturbances as possible. Trifocal IOLs based on EDoF technology seem to fulfill all these criteria.
In addition to the IOL types mentioned above, there is another relatively rare type, accommodative IOLs. They do not have a multifocal design but can use the contraction of the ciliary muscle to change the diopter of the IOL to achieve visual ability at different distances. This type of IOL retains ciliary muscle function through complex processes and aims to restore the regulation of the normal human lens76. However, this kind of IOL has not been widely used in the clinic, and there is only one approved IOL by the FDA: the AOU1V/AOU2V (Crystalens; Bausch & Lomb) 77. There are still only a few studies on this kind of IOL, but we believe that this type of IOL will gradually mature and become widely used in the clinic.
Aside from technical developments, we are most concerned about the growing visual needs of patients. Patient satisfaction is an important criterion to evaluate an IOL. In some studies, during the development phase, questionnaires were used to obtain some patients' subjective perceptions of the IOL49, 50, 51, which we think is an appropriate method. We hope that there will be better or specially designed questionnaires for postoperative cataract patients and that more researchers will consider patients’ views and needs. Clinicians need to ask detailed questions when choosing an IOL for patients preoperatively and select a PIOL that best fits their needs and lifestyle.