Tisilfocon A The Evidence to Support Permeability of 180+

This article from Menicon’s Steve Newman explores the findings of a company white paper.

Menicon has always been focussed on the development of state-of-the art contact lens and intraocular lens (IOL) soft and rigid materials. Driven by an initiative of the company’s founder, Kyoichi Tanaka, to create the safest contact lenses possible, Menicon material scientists worked to improve key material characteristics that could achieve this goal.

To that end, in 1987 an early rigid gas permeable (RGP) material development program was instigated to create a clinically optimised lens with the highest level of oxygen permeability in the world. This culminated in the development of a highly successful and patented RGP material called tisilfocon A (Menicon Z).

The tisilfocon A material is a thermoset copolymer derived from fluoro-methacrylate and siloxanylstyrene, bound by crosslinkers. An ultraviolet (UV) absorber, benzotriazole, is incorporated in the material. Menicon Z lenses are available in blue and red tints, and in clear form, as well as sphere, toric, multifocal, and orthokeratology (OK) designs.

Despite its extremely high oxygen permeability (Dk), tisilfocon A exhibits a high-rockwell hardness (circa 60), which is comparable to that of medium/high Dk rigid gas permeable (RGP) materials.

Menicon Z received United States Food and Drug Administration (FDA) approval (K962006) for daily wear in 1996 and achieved the goal of having the highest Dk in the world of RGP materials. It remains there to this day.

Subsequently, in 2000, it was FDA approved (P990018) for continuous wear of up to seven days.

Additionally, tisilfocon A became the only FDA approved RGP material in the US for up to 30 days continuous wear. Today, this material is used to manufacture all types of lens designs and configurations, from corneal lenses to scleral shells.

While not required for successful clinical performance, Menicon combined its breakthrough material with a plasma surface treatment. The combination of the tisifilcon A material and plasma surface treatment produced a highly wetting material that demonstrated optimal in vivo performance. The use of a plasma treatment allows for periodic protein removal regimes with no deterioration of the surface behaviour. This combination has proven to be advantageous in overnight OK, where both a high level of oxygen transmission and the maintenance of a pristine surface is paramount to clinical performance and safety.

TESTING THE COMPETITION

Recently, there have been developments in the hyper Dk material space. The expiration of Menicon Z patents triggered particular interest within the material industry with similar material formulations being synthesised and brought to market with claims of being the “world’s highest Dk”.

Menicon tested a number of its own tisilfocon A (Menicon Z) material lots against externally sourced Optimum Infinite (tisilfocon A) material samples supplied with a claimed Dk of 200 Fatt units.

Additionally, in 2019 Menicon engaged Dr William J. Benjamin OD MS PhD FAAO and the company Material Performance Assessments to perform a comparative Dk study between tisilfocon A (Menicon Z) material and Optimum Infinite (tisilfocon A).

The Menicon white paper summarises the results of these assessments, which confirmed that the tisilfocon A RGP material – whether from the original creator or as represented by other material manufacturers that have emulated the material formulation – still possesses a Dk which, being over 180 Fatt units, rates in the highest commercially available RGP materials in the world today.

DK REFERENCE MATERIALS

Dr Benjamin and his co-author, the late Quido A. Cappelli addressed the issue of establishing RGP Dk standards in their 2002 landmark paper, Oxygen permeability (Dk) of thirty-seven rigid contact lens materials. ¹

In this paper, the authors described the historical approach manufacturers have used to market Dk values of various RGP materials with an inherent tendency for overstatement. They also described attempts made (by the authors and the Contact Lens Manufacturers Association (CLMA)) to bring a standard to bear for all manufacturers to use. The CLMA was able to access the majority of RGP materials used in the US and generated sample lenses of each candidate material via a single laboratory. All materials were masked and coded until all manufacturing and measurements were completed.

Each material type was submitted in six different thicknesses and four measurements of each sample were taken, resulting in 24 measurements being taken per material type. The mean preliminary amperages provided were corrected Dk values according to the American National Standards Institute (ANSI) 80.20-1998 standards. The outcomes were linearly calibrated using the previously established reference materials.

The culmination of these efforts was a repository of RGP materials produced by the major contact lens producers, with ‘standards’ that could be used by all laboratories for comparison against their own materials and for referencing oxygen transmissibility (Dk/t) outcomes in their respective lens designs.

The measured samples were confirmed as conforming to the ANSI Z.8020-1998 tolerance for Dk (+/- 20%) and measurement reproducibility of +/-10%.

Three sets of Menicon sample materials were obtained, including Menicon Z (two lots) and Menicon SF-P (one lot).

Menicon SF-P exhibited a Dk range (with 95% confidence of 117.2–155.7 and a corrected, calibrated oxygen permeability (Dk in ANSI units) of 133.6. The two Menicon Z sample groups resulted in Dk ranges of 142.1–186.2 and 154.9–201.6 with corrected, calibrated oxygen permeability (Dk in ANSI units) of 161.1 and 175.1, respectively.

Menicon has always preferred to err on the side of caution when making product claims, and elected to use the lower Dk value for product registration submissions and marketing. Despite this choice, the Menicon Z material was still able to be marketed as having the highest Dk in the world.

HOW MUCH OXYGEN IS ENOUGH?

According to Dr Benjamin, the answer to the question of “How much oxygen is enough?” is: “Menicon SFP with a Dk roughly of 135 units and the Menicon Z with a Dk of between 160 and 175, depending on what batch of material is measured. Extended wear with these lenses is possible and is not limited by their Dk or Dk/t.”

TESTING THE MATERIALS

Dr Benjamin received contact lens samples of Menicon Z RGP contact lens material samples and Optimum Infinite samples, by Valley Contax.

The sets were each made of a material named tisilfocon A, and were of RGP contact lenses designated with codes indicative of the nominal thicknesses: 0.11, 0.14, 0.18, 0.23, 0.29, and 0.40 mm (Table 1).

There were two test lenses of each test material per thickness, leading to a total of 24 tested lenses. The Dk value of the test materials was thought to fall above that of the tisilfocon A reference material maintained at Material Performance Assessments.^2,3

Two six-lens thickness series of the reference material tisilfocon A (Menicon Z), one fivelens thickness series of the reference material siflufocon B (Quantum 2), and one six-lens thickness series of the reference material paflufocon C (Fluoroperm 30) were selected for calibration of the test Dk values during preparatory communications.

The test sets were designated ‘Set A’ (Menicon Z) and ‘Set B’ (Optimum Infinite) in the tables, below. The central thickness of each test sample was measured five times with a calliper gauge, independently, and the mean central thicknesses were calculated.

The test lenses were of uniform thickness, such that their thicknesses were nearly constant across the optic zones of the samples. Two series of six samples resulted from Set A (Menicon Z) and two series of six samples resulted from Set B (Optimum Infinite).

The approximate (nominal) thicknesses of reference rigid lenses were 0.11, 0.14, 0.18, 0.23, 0.29, and 0.40mm. These were tisilfocon A (Menicon Z) reference series R7a and R7b, siflufocon B (Quantum 2) reference series R5, and paflufocon C (Fluoroperm 30) reference series R2.

The reference lenses were also of uniform thickness, such that their thicknesses were nearly constant across the optic zones of the lenses. The central thicknesses of the reference lenses had each been measured four times with a calliper gauge, independently, and the means were computed. [For lenses of uniform thickness, the central thickness is also the mean harmonic central thickness.]

Six lenses of the R2, R7a, and R7b reference series and five lenses of the R5 reference series (23 reference lenses in total), in the uniform nominal thicknesses noted above, were assessed polarographically for oxygen transport in the same sessions and in the same manner as were the 24 test samples. The oxygen assessments were performed in a humidity-saturated environment at 35°C using an oxygen permeometer and sensor.

The test and reference lenses were stored prior to polarographic measurement at 35ºC, in vials containing a standard saline as designated in ANSI Z80.20:2016⁴ and the International Organization for Standardization (ISO)18369-4:2017.⁵ Test and reference lenses of a similar thickness were evaluated in a single session, and four sessions were completed for every thickness series. The measurements were performed according to a schedule designed to spread the potential effects of machine drift and alterations of ambient conditions. The test gas was 20.9% oxygen with barometric pressure fluctuating around 745 mmHg. In all, a total of 188 polarographic measurements of preliminary Dk/t were accomplished.

A filter paper bridge was used for the test and reference lenses. The preliminary amperages were the basis for computation of preliminary oxygen transmissibility (pre-Dk/t) values according to ANSI Z80.20:2016 and ISO 18369-4:2017,⁵ as well as for subsequent corrections for the boundary-layer effect and the Type I edge effect.

The corrected, uncalibrated oxygen permeability (Dk) values for the reference materials were the result of four preliminary transmissibility (pre-Dk/t) determinations for each reference sample, or a total of 24 pre-Dk/t measurements for the R2 thickness series, 20 pre-Dk/t measurements for the R5 series, and 48 pre-Dk/t measurements for the R7 reference.

The corrected, uncalibrated oxygen permeability (Dk) values for the test sets were also each the result of four preliminary transmissibility (pre-Dk/t) determinations per test sample. The test materials were both represented by two thickness series of samples. Hence, the overall Dk values of the test materials were the result of determinations on 12 lens samples of Set A and Set B, or a total of 48 pre-Dk/t measurements of Material A and 48 preDk/t measurements of Material B. The uncalibrated Dk values were calculated from the inverse slopes of the corrected resistance (t/Dk) vs thickness (t) plots in Figures 1.

The corrected oxygen permeability (Dk) values of the test materials (n=12 lenses) were then calibrated using a linear equation derived from the determined and established standard Dk values of the reference materials.2,3 The final corrected and calibrated Dk values are reported in Fatt Dk units in Table 2.

TESTING THE MATERIALS INTERNALLY AT MENICON

Menicon tested its own tisilfocon A (Menicon Z) material lot against externally sourced Optimum Infinite (tisilfocon A) material samples that were supplied with a claimed Dk of 200 Fatt units. The testing, including evaluation of all relevant material properties, was conducted at Menicon’s research facilities in Japan.⁶

The Dk studies were conducted using a GTG Analyzer/Rehder Development Company, and the results are shown in the Tables 3–5 and Figure 2. As can be seen via these comparative measurements, tisilfocon A (Menicon Z) and tisilfocon A (Optimum Infinite) share a common formulation basis and exhibited similar characteristics, including a permeability of around 180+ Fatt units.

SUMMARY

Many years ago, Menicon placed a high priority on the development of a new generation RGP material that would exhibit the best possible level of clinical performance and patient health. The requirements of such material included the highest level of oxygen permeability ever achieved, optimal spectral transmissibility, and physical characteristics that would allow eye care professionals to provide an accurate, consistent, stable, and safe fitting experience for their patients. Increasing Dk levels substantially via the addition of various silicone monomers is usually associated with a softer, more malleable material that may not provide the most accurate or consistent fitting capabilities. Additionally, softer, high Dk RGP materials are harder to produce by lathing, which tends to inhibit the ability of the manufacturers to obtain the highest quality parameter tolerances and surface finishes. Menicon was able to increase the Dk substantially without compromising the optimal physical hardness and stiffness requirements.

Menicon has achieved its goals in creating a safe and high-performance RGP material and has maintained the quality and consistency of its production since the 1990s. The key criteria for achieving the highest Dk levels, without adversely affecting clinical performance, has been demonstrated with over a quarter of a century of successful patient outcomes around the world. Its choice of material design has also been validated by the introduction to the market of a product that emulates Menicon Z (Optimum Infinite), sharing both the USAN and similar Dk performance. While initially taking a conservative approach to making any permeability claims, in this report Menicon has been able to demonstrate that the intrinsic properties of the tisilfocon A (Menicon Z) RGP material has consistently exhibited Dk levels of over 180 Fatt units, thus being the RGP contact lens material with the highest Dk in the world.

Steve Newman is the Senior Technical Director for Menicon Co Ltd.

References

1. Benjamin, W.J., Cappelli Q.A., Oxygen permeability (Dk) of thirty-seven rigid contact lens materials. Optom Vis Sci. 2002 Feb;79(2):103–11. DOI: 10.1097/00006324- 200202000-00012. PMID: 11868847.
2. Benjamin, W.J., and the Dk Reference Study Group. Revised oxygen permeability (Dk) of reference materials. Investigative Ophthalmology & Visual Science 47:ARVO EAbstract 97/B385, 2006.
3. Benjamin, W.J., and the Dk Reference Study Group. Comparison of oxygen permeability (Dk) calibrations. Optometry & Vision Science 83:AAO Abstract 065294, 2006.
4. ANSI Z80.20–2016: American National Standard for Ophthalmics – Contact Lenses – Standard Terminology, Tolerances, Measurements, and Physicochemical Properties. American National Standards Institute (ANSI), Z80 Committee on ophthalmic optics.
5. ISO 18369-4:2017. International Standard, Ophthalmic optics–Contact lenses–Part 4: Physicochemical properties of contact lens materials. International Organization for Standardization (ISO).