Gradient refractive index optics IOL: theoretical background and clinical results.

PURPOSE: To present the theoretical optical background and clinical results of a new multifocal intraocular lens (MIOL) concept-gradient refractive index optics (Gradiol). PATIENTS AND METHODS: Original mathematical modeling software was used to calculate optimal construction of the MIOL optic constructed from two polymer materials with different refractive indices. Gradiol lenses were manufactured from hydrophobic acrylic utilizing original step-by-step polymerization technology with the final power difference of of 3.5 D between optic components. Non-comparative prospective clinical study included 26 patients (29 eyes) who were candidates for MIOL implantation. All surgeries were performed at the S. Fyodorov Eye Microsurgery Complex State Institution, Moscow, Russia. After implantation of the Gradiol lenses, the postoperative evaluations included distance (best corrected visual acuity (BCVA)) and near visual acuity (NVA), contrast sensitivity (CS), and amplitude of pseudoaccommodation. Subjective patient's satisfaction was assessed using a questionnaire (VF-14).
RESULTS: The mean age of the patients was 62.5 ± 5.7 years (range 27-82 years). All surgical procedures were uneventful. At 6 months postoperatively, the mean uncorrected distance VA was 0.73 ± 0.18, mean uncorrected near VA was 0.57 ± 0.19, mean corrected distance VA was 0.89 ± 0.15, mean corrected near VA was 0.84 ± 0.07, and amplitude of pseudoaccommodation was 4.75 ± 0.5 D. Eighty-six percent of patients were spectacle independent for daily activities and reading. Optical disturbances that were functionally significant were reported by 10.7% of patients postoperatively.
CONCLUSION: The clinical outcomes of this study confirmed the theoretical calculations of constructing MIOL optics from materials with different refractive indices.

INTRODUCTION

Currently diffractive and refractive multifocal intraocular lenses (MIOLs) are often used for refractive lens exchange and presbyopia correction.123456789101112 The principle of MIOLs involves subdividing incoming light into at least two components that form focal zones of specific depths. MIOLs represents an optical compromise between high quality visual function in variable luminance conditions and the ability to see at various distances. Fundamentally, multifocal correction is a correlation between depth of focus and modulation transfer functions (MTFs) of the optical system. The MIOL design that provides better quality of vision and independence from spectacle correction continues to be debated.

Presently, the lenticular theory is the dominant theory of presbyopia. This theory proposes that the main causes of presbyopia are the changes over time in optical and biomechanical parameters of the physiologic lens.13141516171819202122 This theory incorporates well-established data including annual growth rate of the crystalline lens (0.02 mm/year), changes in mean equivalent refractive index (1.427 ÷ 1.418) and surface refractive index (1.386 ÷ 1.394).2223242526

Changes in the physiologic lens result in a decrease of negative spherical aberration towards positive spherical aberration in individuals of presbyopic age. This change in spherical aberrations and magnitude of the spherical aberration can have a number of optical consequences including changing the depth of focus. If depth of focus increases, it can results in a “passive” ability of the eye to see at various distances without an active change of lens power during accommodation.27 We tried to emulate this physiologic process that can be modeled by gradient optics while developing a MIOL.

Currently available MIOLs have variable refractive power due to the complex shape of anterior and/or posterior surfaces. However, gradient optics is characterized by varying refractive power due to a change of refractive index in inner structure of the IOL. This feature results in a number of optical and structural advantages. This design will likely improve functional results and diminish optical side effects in patients who undergo MIOL implantation.

In addition to mimicking normal physiology, there are other potential benefits of gradient IOLs compared to other MIOL design including

A smooth optical surface decreases the possibility of mechanical damage to the lens optic during implantation;

Postoperative functional vision is achieved over a wide range, including near and intermediate distances which is of utmost important for computer work and driving;

Good visual functions under varying light conditions (photopic, mesopic, and scotopic);

Better retinal image quality postoperatively.

The purpose of the current study was to use theoretical research to develop, and clinically evaluate a MIOL with gradient refractive index optics. We tried to emulate this physiologic process that can be modeled by gradient optics while developing a MIOL. The goal of our study was to create a IOL with sufficient pseudoaccommodation (up to 5.00 D), which corresponds to the normal accommodation values of 40-45-year-old subjects.28

Computer modeling of human eye optics with implanted multifocal gradient intraocular lens

Original mathematical modeling software was developed based on fundamental optical principles. This software used optimize gradient IOL parameters in or to simulate the highest image quality possible. The software performs calculations for the optics of the human eye. This software can construct and analyze test object images by ray tracing in the axial and transverse planes, to model and visualize the color images projected on the retina. Additionally, comparative quantitative analysis can be performed of the optical characteristics of the IOL (modulation transfer and scattering functions) while changing varying parameters (diameter, surface curvature radius, and refractive index).

Theoretical basis and software algorithm

The software is based on the calculation of light rays, each of which is incident to the lens surface at arbitrary point under variable angles. The only simplifying assumption fully fulfilled in all designs is the lens axial symmetry. The IOL surface can be modeled as spheric, ellipsoid, hyperbolic, or parabolic. The software calculates convex, concave, convex-concave, and concave-convex lenses. Calculation of each ray is performed according to the laws of geometric optics in a three-dimensional space.

To simulate an image of a point source of light, it is necessary to calculate the light ray data emitting from the given source and passing through the lens at different locations in a transverse fashion. Visualization of software simulation allows an understanding of the emission pattern and image type formed by the light rays. Mean focal distance calculation results in plotting a focal distance-principal optical axis distance diagram, which provides information on spherical aberration of the lens. This information is also garnered from the value of the standard deviation of the focal distance. Spherical and higher order aberrations are calculated according to the software algorithm. The algorithm is easily extrapolated to the system of lenses and can be modified for calculation of lenses with complex surface structure including gradient optic lenses.

SOFTWARE WINDOWS

Determination of optimal optical parameters for a gradient multifocal intraocular lens

The calculations were performed by software consisting of visual programming environment Borland C++ Builder (version 6) with the Windows XP operating system (Microsoft Corp., Redmond, WA, USA). The program operating window is presented in Figure 1 that demonstrates a software version for a particular gradient lens calculation, which consists of outer and inner components. The latter has a smaller diameter differing from the outer component by external surface radii and refraction index. The software accounts for a considerable number of optical system parameters including cornea, aqueous humor, artificial lens, vitreous body, and retina. IOL parameters are set either as optical components diameter, curvature radius, refraction index, IOL thickness, lens sphericity in relation to the optical axis, and diaphragm diameter (i.e., pupil).

Figure 1

Software window. Modeling rays passes through gradient lens thus determining focal zone parameters

The human eye optical parameters include radius of curvature of the outer corneal surface (7.7 mm), inner corneal surface (6.8 mm), outer corneal surface-retina distance (24.0 mm), retinal curvature radius (12.0 mm), cornea refraction index (1.376), aqueous humor (1.336), and vitreous body (1.337).

Computer modeling software allowed analysis of the distribution of rays and ray patterns in the principal focus neighborhood and types of aberrations. Figure 2 demonstrates the ray transmission near multifocal gradient lens focus reflecting correlation to optimal lens parameters. The software plots focal distance-ray position to lens optical axis diagram (if the source is positioned at the principal optical axis and sufficiently distant from the lens) [Figure 3]. The diagram provides information on the spherical aberrations of a given lens. The focal distance standard deviation value provides information on spherical aberration. All other lens aberrations are calculated according to the software algorithm.

Figure 2

Rays transmission nearby multifocal gradient lens focus. Outer lens component refraction index (RI) is 1.5035, inner component RI - 1.4835

Figure 3

Focal distance-ray radial coordinate diagram

The software enables simulation and analysis of point light sources located at various distances from principal optical axis of the lens. Figure 4 demonstrates the light scattering sources around the maximum concentration zone of the light beam that is attributed to one of the multifocal lens foci.

Figure 4

Point light source image formed by multifocal lens

Simultaneous analysis and visualization of spherical and chromatic aberrations by the software allows simulation of color images of test objects formed on the retina of a pseudophakic eye. To obtain image quantitative estimation, the computer modeling software calculates MTF and scattering function.

In order to calculate and select multifocal gradient IOL optimal parameters, we performed comprehensive computer modeling data evaluation. Additional optical power (difference in refractive power between zones for far and near) was specified by optimal distance for near vision (30/33 cm) and was determined by a refraction index (1.520 and 1.4795 for outer and inner components correspondingly) and by components curvature radius (15.11 mm outer lens component, 13.66 mm inner). Optimal calculated value of refractive power difference for far and near (outer and inner components of the lens) was 3.0 D.

For the retinal image computer modeling data, priority was place on distance vision for pseudophakic patients, safe driving (especially for acute miosis under bright light), and the possibility of senile miosis. Hence, the central optical zone was designed for far vision. The diameter of the inner component was calculated with consideration of optimal redistribution of light rays under varying light conditions (variable pupil diameters).

The optimal calculated value of the inner component diameter was modeled for 2.0 mm (3.0 mm pupil diameter). Under photopic conditions the distribution of light rays between far and near zones was 45 and 55%, respectively (inner component diameter 2.0 mm). Under bright light and 2.5 mm miosis the redistribution of light rays occurs at 65 and 35%, respectively. Under mesopic conditions and 3.5-4.0 mm pupil diameter, the distribution of light rays for far and near zones was 30 and 70%, respectively. The overall diameter of the optical zone is 6.0 mm. The inner component is placed in the center of outer component on radius and thickness. The overall IOL thickness is 1.0 mm, and its central component is 0.4 mm.

A single piece foldable multifocal gradient IOL was manufactured with step-by-step polymerization technology in transfer molds of photohardening material (ultraviolet light) with various refraction indexes (oligourethan-methacrylate). This technology can produce multifocal artificial lenses with gradient optics. The relative simplicity is an advantage of the manufacturing process, hence it is possible to combine stages of material polymerization with lens manufacturing concurrently. Additionally, polymerization in the mold determines better optical characteristics of the lens in comparison to lens milling by achieving better surface quality and minimizing optical aberrations in the IOL.

The Gradiol IOL is a joint invention and the result of collaboration between the S. Fyodorov Eye Microsurgery Complex (B. Malyugin, T. Morozova) and REPER-NN (V. Treushnikov, E. Viktorova), a lens manufacturing company. Figure 5 demonstrates the general view of pseudoaccomodation with the Gradiol MIOL with gradient optics.

Figure 5

General view of multifocal intraocular lens with gradient optic (photo)

CLINICAL STUDIES

Patients and methods

This study was conducted according to the principles of the Declaration of Helsinki and was approved by the local ethical committee. All patients were adequately informed and signed a consent form.

Twenty-six patients (29 eyes) were prospectively enrolled with age ranging from 27 to 82 years. This noncomparative study included 11 males and 15 females. All patients had cataracts mean visual acuity deterioration of 0.11 ± 0.09. Exclusion criteria were astigmatism greater than 1.0 diopter; anterior segment pathology such as chronic uveitis, zonular dialysis, pseudoexfoliation syndrome, glaucoma, diabetic retinopathy, and age-related macular degeneration. Patients with previous anterior and posterior segment surgery and intraoperative or postoperative complications were also excluded. All eyes were targeted for emmetropia postoperatively using the SRK/T formula.

The surgical procedure included phacoemulsification through a 2.2 mm clear corneal incision under topical anesthesia. The IOL was implanted in the capsular bag with an injector [Figure 6]. At the end of the surgery the incisions were hydrated.

Figure 6

Implantation of Gradiol trailing haptic element into the capsular bag

All patients were discharged 1 h after surgery. Postoperative medications included topical moxifloxacin and dexamethasone 0.1% QID for 3 weeks.

Patients were scheduled for clinical evaluation preoperatively, and 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Additional visits were scheduled if necessary.

No major complications were observed during the early or late postoperative periods.

Outcome measures

A standard comprehensive ophthalmic examination, including manifest refraction, biomicroscopy, intraocular pressure measurement, and funduscopy was performed at all visits. Uncorrected and best-corrected distance visual acuities were measured with decimal charts. Uncorrected and best corrected near visual acuities were measured with reading charts (Russian validated version). Uncorrected and best corrected distance visual acuities, monocular uncorrected and best corrected near visual acuities, and best distance-corrected near visual acuity (NVA) were recorded at 5 m for distance measurements and 33 cm for near measurements in all patients. All visual acuity measurements were performed monocularly.

Refraction was measured with an autorefractor and retested subjectively.

Methods used for pseudoaccomodation testing included

Sphere addition- assisted defocusing with 1.0 D step at corrected visual acuity (VA) for far 0.8 using an accommodometer; and

sphere addition- assisted defocusing with 0.5 D step at corrected VA 0.5 using conventional optotypes.

Contrast sensitivity (CS) was measured with Optec-3000 (Stereo Optical Company, Inc. Chicago, IL, USA).

To perform a quantitative analysis of visual dysfunctions we employed the VF-14 patient questionnaire (VF-14).29 To further assess functional needs and specific characteristics of multifocal correction we included additional questions on the ability to use a computer without spectacle correction (to evaluate vision at intermediate distances) and details of optical distrubances (type and level).

CLINICAL RESULTS

Distances visual acuity

Distance VA improved in all cases after phacoemulsification after implantation of gradient MIOL. Analysis of data on distance uncorrected and corrected visual acuity at various follow-up periods (1, 3, and 6 months) proves stability and good functional visual acuity [Table 1].

Table 1

Mean far visual acuity postop

Better functional results were obtained in patients with slight hyperopia of ± 0.5 D sphere, ±0.5 D of against-the-rule corneal astigmatism, and 1.0 D with-the-rule corneal astigmatism. Mean spherical equivalent was + 0.09 D.

Near visual acuity

Data on uncorrected and best corrected visual acuity for near at various follow-up periods (1, 3, and 6 months) also proved stability and good functional visual acuity [Table 2]. These data indicate full visual rehabilitation and high scores on the subjective evaluation postoperatively. Near VA outcomes indicated that reading could be performed without additional spectacle correction.

Table 2

Mean near visual acuity postop

Evaluation of near VA with full distance correction is presented in Table 3. This measure assesses visual function specific to MIOLs. Additional distance correction in cases of residual myopic refraction decreases NVA compared to uncorrected near VA. Additional correction for far in cases of residual hyperopic refraction either increases or has no effect on near VA compared to near VA without correction. The latter determines residual hyperopic refraction postoperatively, which is more preferable.

Table 3

Best distance-corrected near visual acuity (VA; 16 cases) and patient's postop refraction

Pseudoaccomodation amplitude

The difference in power between optical zones should provide a calculated pseudoaccomodation amplitude of at least 3.00 D. The pseudoaccomodation after gradient IOL implantation was 4.75 ± 0.50 D [Figure 7].

Figure 7

Defocus curve after Gradiol implantation

There was an even distribution of light energy among all optical zones (for far, near, and intermediate distances). The defocus curve was smooth with peak at the point of maximum corrected distance VA.

Contrast sensitivity testing

CS testing is one of the basic components of comprehensive clinical evaluation of postoperative visual outcomes. Previous studies have confirmed that CS and mesopic visual acuity (with/without glare) are diminished after MIOL implantation compared to normal values.

In the current study, there was no change in CS compared to normal values across all spatial frequencies after multifocal gradient IOLs implantation [Figure 8].

Figure 8

Data on spatial contrast sensitivity testing after Gradiol implantation. Three months postop

Optical disturbances

Optical disturbances included light streaks, halos, flare, flashes, and glare.30 Halos and glare were the most frequent complaints. The grades varied from subtle to pronounced [Table 4]. There was no tendency for these optical disturbances to decrease over long-term follow-up.

Table 4

Optical phenomenons

The cause of the optical disturbances is likely the separation of light at the focal zones as well as the presence of distinct borders between the inner and outer optics. The majority of patients (57.1%) noted optical disturbances during history taking, and only 10.7% of cases were functionally significant. Mostly patients complained of halos under scotopic conditions and a “blinding” effect from oncoming headlights while driving at night. None of the patients required MIOL explantation due to night vision disturbances.

Of all the patients with optical disturbances postoperatively, 81.3% had residual myopic refraction. Residual myopia increases light scatter resulting in an increase of the optical disturbance and decreasing patient's quality of life.

SUBJECTIVE QUESTIONNAIRE

The mean VF-14 score was equivalent to 100 indicating high subjective satisfaction after Gradiol implantation. Postoperatively, 86% of patients were able to perform near tasks without spectacle correction, including prolonged work at near, small print text reading, as well computer work under varying light conditions (bright and dim light).

DISCUSSION

It is possible to theoretically calculate the light beam distribution in optical models of the human eye, including the modulation transfer and scattering functions and perform retinal image quality modeling. However, simulation of the effect of neural processing on visual functions after MIOL is not possible. Hence, the final conclusion on the efficacy of a specific MIOL can only reached after clinical trials. The functional outcomes for far and near vision and pseudoaccomodative amplitude indicate the Gradiol is efficacious.

The outcomes for distance visual acuity after Gradiol implantation is comparable to diffractive and refractive MIOLs. For example, after ReSTOR® IOL implantation (diffractive/refractive; Alcon Inc., Fort Worth, TX, USA) the uncorrected distance VA was 0.8 in 54% cases and uncorrected near VA of 0.5 was achieved in 100% of the cases and 0.8 was achieved in 52% of the cases.3132 A multicenter trial of the AMO Array® (refractive IOL) reported distance uncorrected VA of 0.7 or better was achieved by 73% of cases, near VA of 0.5 or better was achieved by 85% of cases. Another study,33 reported mean binocular uncorrected distance VA after ReZoom® refractive MIOL implantation was equal to 1.0, and 0.5 for near.

Patients who have undergone refractive and gradient IOL implantation, have better intermediate vision (from 40 cm to 1.0 m) compared to patients who have undergone diffractive IOL implantation. Intermediate vision is important for driving (dashboard control) and computer work.

CS testing the current study was comparable with previous outcomes from diffractive MIOLs and refractive AMO Array.34 In previous studies CS in both groups at low and high spatial frequencies was identical to the normal values.34 Compared to refractive MIOLs, CS in patients with diffractive MIOLs was lower at mid-spatial frequencies.34 Glare testing CS in the first group was significantly lower than normal values.34

We consider subtle decrease in CS at all spatial frequencies as an important specific feature of multifocal gradient IOLs. We believe this characteristic enables visual work under varying light conditions and adequate functional rehabilitation of patients postoperatively. The comparison of CS in our study and other studies seem to that gradient and refractive MIOLs have advantages over diffractive MIOLs as the latter result in impaired CS and increased glare.

Postoperative optical disturbances are important for functional assessment of the MIOL implantation. We found clinically significant disturbances in only 10.7% of cases. However, there was no regression of symptoms with long-term follow-up. Often neural processing adapts to these disturbance, ignoring them over time. Therefore, most of the patients noted optical disturbances only after meticulous discussion (57%). Theoretically, these disturbances can be explained by light reflection from the transition zone and IOL surface and light diffraction at the border of the optical components.

Comparative analysis of our data to other studies of optical disturbances indicated similar outcomes for different types of MIOLs. Haring et al.,30 reported optical side effects in 9% of patients after monofocal IOL implantation and in 41% of cases after refractive multifocals. Halos and glare are the most frequent complaints in patients after MIOL implantation compared to monofocal IOLs. Takhtayev and Balashevich31 studied symptoms after Acrysof ReSTOR (Alcon Inc., Fort Worth, Tx, USA) implantation and observed visual impairment in twilight conditions in 8% cases, optical side effects near point sources of light in 11% of cases, and impairment on glare testing in 14% of cases. The symptoms were of moderate severity.31 To reduce the symptoms or optical disturbances reported the current study, refinement of the IOL design is required such as relatively homogenous transition zones or elimination of transition zones.

Conventional visual acuity testing is the most widely used test for evaluation of functional outcomes. However, this test does not reflect patient satisfaction and does not provide information on the effects on work or quality of life. Subjective testing in all MIOLs groups demonstrated high patient satisfaction postoperatively. Previous reports of patient satisfaction vary considerably indicating a range of 32-81% of patients who did not require additional spectacle correction.43536373839 In our study, 86% of patients did not use spectacle correction for work at distance and near including during prolonged activity and driving.

Based on these results, the current clinical trial proved safety, efficacy, and stability of results determining adequate visual rehabilitation and high patient satisfaction. These results are encouraging and provide the impetus for further design enhancements to existing MIOLs or the creation of new models.

Our initial results are essential in the development of optics with gradient change in refraction index. The most significant disadvantage of the Gradiol MIOL is the postoperative optical disturbance which has also been reported with other multifocals. Refined designs may mitigate these symptoms. We are currently conducting a clinical trial of a new generation of gradient MIOLs with no transitional border between the two optical zones.