Some recall the rapid development of soft, hydrophilic contact lenses in the U.S. once Bausch + Lomb introduced the first poly-2-hydroxyethyl methacrylate (polyHEMA) contact lens in 1971.¹ It was produced using a spin casting process based on the work of Otto Wichterle, whose first successful trial had occurred 10 years earlier as a Christmas day experiment in his kitchen.²

Although much work was ongoing by others using other hydrophilic monomers and processes, this manufacturing advance was the key starting point for soft contact lens wear. Today, it is estimated that more than 45 million people in the U.S.³ and 140 million people globally wear soft or rigid contact lenses.⁴

NON-HYDROGEL MATERIALS & CARE

The first soft contact lens made from polyHEMA was heat disinfected in a preserved or non-preserved saline solution nightly and replaced annually.⁵ Soon after its approval by the U.S. Food and Drug Administration (FDA), 59 new approval applications were submitted.⁶ As time progressed, the polymers used in soft contact lenses were improved by a variety of other monomers, both ionic—such as methacrylic acid (MA)—and non-ionic—such as N-vinyl pyrrolidone—to increase the water content. This was not without issues.

Deposit formation from ocular components and the interaction with preservatives used in the saline solutions filled the literature causing fouling of the lenses, and in some cases—such as use of the mercury-based preservative thimerosal, or disinfecting agents designed for use with rigid lenses—resulted in allergic reactions.⁷ Documented as early as 1984, ionic monomers such as MA interacted with lysozyme to form deposits, while preservatives, such as sorbic acid, in novel saline solutions that were developed for heat disinfection would discolor the lenses.⁸

With the developing differences in the materials and their performance and interaction with their environment, soft contact lenses were divided into groups based on water content and ionicity. The initial grouping of contact lenses proposed by Stone⁹ was accepted by the FDA, incorporated into ISO standards¹⁰ and also adopted in Japan.¹¹ The lens grouping system was developed to assure compatibility with care systems. The groupings as accepted are shown in Table 1.

The ability to chemically disinfect lenses using hydrogen peroxide, polyaminopropyl biguanide (PHMB), polyquad, alexidine, and aldox phased out heat disinfection units over time. Another approach was to avoid care products entirely by either daily replacement or extended continuous wear for up to one week.

FDA approval in the U.S. for up to 30 days of extended wear was initially dominated by the higher-water, higher-Dk materials. Later, this approval was reduced to seven days.¹² Today, it is quite common to use a multipurpose solution (MPS) for a combination of wetting, cleaning, and disinfection purposes for patient convenience.

OXYGEN PERMEABILITY AND TRANSMISSIBILITY

In 1984, Holden and Mertz reported that hydrogel polymers relying solely on water to transport oxygen was insufficient in avoiding corneal edema with overnight wear.¹³ Their study found that with daily wear, a contact lens with an oxygen transmissibility (Dk/t) of 24.1 did not cause corneal edema. This could be achieved with low-water-content polyHEMA lenses (e.g., polymacon 38%) with a Dk of 8 and a maximum thickness of 33 microns. For overnight wear with zero residual swelling shortly after awakening, this could be achieved with high-water materials with a Dk of 40 and a maximum thickness of 117 microns.

However, for overnight wear with no swelling above 4%—the level of corneal edema experienced with no lens in a closed-eye environment—only higher-Dk silicone-based materials could meet this criteria. Lower-Dk hydrogel lenses would require a thicknesses of 9 microns (low water content) or 46 microns (high water content) not achievable in manufacturing.

Hydrogel lenses with a Dk/t ranging from 10.3 to 38.1 produced 7.2% to 14.9% corneal swelling overnight, the lesser with higher-water-content hydrogels. In comparison, pure silicone materials with no water exhibited only 2.6% swelling.¹³ Also associated with this swelling effect were observations of acidosis, increased limbal hyperemia, epithelial microcysts, and endothelial responses.¹⁴ These signs were reduced with the advent of silicone hydrogels.¹⁵

WHAT WAS LEARNED FROM THE FIRST 20 YEARS OF SOFT HYDROGEL LENS WEAR?

1. Oxygen transmission to the cornea is critical for successful overnight wear, and relying on water transport alone may not be sufficient to prevent corneal edema.¹³
2. The use of charged molecules to increase water content can lead to higher levels of deposit formation and interaction with tear components (FDA Group IV).¹⁶
3. The care of contact lenses is important, and testing standards are important during the development of key approaches to disinfection. The continued use of hydrogen peroxide, and the development of other key disinfecting compounds, could provide alternative safe approaches to reusing lenses, but must be carefully evaluated with new care formulations and lens materials.
4. Overnight wear continues to be a risk factor for infection, wearing lenses during sleep periods.¹⁷
5. Swimming and showering while wearing contact lenses are risk factors for infections in contact lens wear.¹⁸

RACE TOWARD SILICONE HYDROGEL MATERIAL

The critical problem in the development of silicone hydrogels was the fact that silicone polymers are inherently hydrophobic and thus incompatible with the ocular environment. Simply co-mixing hydrophilic polymers such as HEMA or methacrylic acid often fails to produce a clear polymer.¹⁹

The earliest approaches to this problem were founded in the late 1970s. The first U.S. patent was issued to Karl F. Mueller and Eduard K. Kleiner at Ciba-Geigy Corp. in January 1979;²⁰ followed by Kyoichi Tanaka and co-workers at Toyo Contact Lens Co Ltd. in Japan, the precursor to Menicon,²¹ and then William G. Deichart and co-workers at Bausch + Lomb a few months later.²² It took another 10 years from these first patents to launch an acceptable silicone hydrogel contact lens in the U.S. market.

The first generation of silicone hydrogels were based on combining macromers with the silicone monomer, 3-[tris(trimethylsilyloxy)silyl]-propyl methacrylate, known as TRIS.²³ Lotrafilcon A (CIBA Vision, now Alcon) was approved for daily wear in May 1997²⁴ and then for overnight wear in October 2001.²⁵ It was described as containing 24% water and a surface treated fluoro-silicone containing hydrogel. It was also described as providing co-continuous water and gel phases.

In February 1999, Bausch + Lomb gained U.S. approval for balafilcon A contact lenses.²⁶ It was a copolymer of a silicone vinyl carbamate, N-vinyl pyrrolidone, a silicone cross linker and a vinyl alanine wetting polymer. It had 36% water content, a Dk of 113.3, and a Dk/t of 101 (–3D lens). Plasma treatment created “glassy islands” with a negative charge on the lens. In November 2001, these lenses were further approved for overnight wear up to seven days.²⁷ These two materials led to the rebirth of overnight wear with oxygen transmissibility recommended for overnight wear based on the criteria set by Mertz and Holden.

The second generation of silicone hydrogels began with galyfilcon A (Vistakon) with a more hydrophilic version of the silicone base patented by Tanaka and coworkers. Galyficon A had a water content of 47% and a Dk of 60.²⁷ The higher water content and lower-Dk value restricted some applications for wear. The addition of the polyvinyl pyrrolidinone provided wettability without the need for a surface treatment.

The third generation of silicone hydrogel technologies incorporated only silicone-containing macromers without added hydrophilic monomers or surface treatments.²⁸ Comfilcon A (CooperVision) had a higher water content of 48% and a Dk of 128. Note the higher water content along with a higher-Dk value. These approaches to the chemistry represent only examples of the technological advancements as we moved from the first silicone-based material, elastofilcon, with a water content of 0.2% and a Dk of 360.

It quickly became apparent that the new silicone hydrogels were not going to fit within the FDA testing groups designed for the standard hydrogel contact lens. It should be noted that these early entries were approved in the U.S. under the original FDA classification system. A fifth category was proposed and was incorporated into the FDA and International Organization for Standardization (ISO) testing groups.²⁹ As silicone hydrogels were developed, group V was expanded to reflect the chemistry of the new materials.²⁹

The classification system was expanded to include Group V in response to the differences in the chemistry of the silicone hydrogels. Hutter asked whether a single grouping (FDA Group V) was sufficient to describe silicone hydrogel performance because solution interaction can depend on the material’s pore size, molecular weight, and surface treatment.³⁰

Stone proposed an expanded Group V in 2007 that reflected many of these differences in silicone hydrogels (Table 2).²⁹ Current ISO standards now reflect some of these subgroup differences (Table 3). But as we continue to approach silicone hydrogel-evolving chemistries, we need to continue to understand the complex chemistries of the silicone hydrogels and their impact on the interactions with the environment for wear and care.

A more recent biphasic material delfilcon A (Alcon) was released as a daily disposable material with a silicone hydrogel core with a water content of 33%, and a bonded water gradient with an average water content of 80% progressing from the silicone core surface to nearly 100% at the surface.³¹ The Dk for the material is reported to be 140.³² Recently, the technology has been refined via the use of a 2-methacrylphosphoryl choline group (lehfilcon, Dk of 123).³³ The improvement provides compatibility with care systems for use as a daily wear lens as well as resistance to bacterial and lipid adhesion.³⁴ The material is designed to build a biomimetic surface and an overall structure that mimics the ocular surface.³⁵

There are currently 21 silicone hydrogel lenses on the market and 15 silicone hydrogel materials available, not including lehfilcon recently added to the market.³⁶

FINAL THOUGHTS

Silicone hydrogels have addressed the need for oxygen in maintaining corneal health, but there is continued research regarding issues of infection, compatibility of lenses with care systems, and other contact lens-related issues. Some issues during the era of silicone hydrogels have been from a lack of attention to other factors that affect lens wear. Daily disposable wear, for example, is not always daily with 10% of patients not complying with the regimen.³⁷ Swimming and showering with contact lenses remain risk factors. Good advice and follow up with patients are critical for long-term problem-free wear. CLS

REFERENCES

1. Bausch + Lomb History + Heritage. Available at https://www.bausch.com/about-bausch-lomb/history-heritage . Accessed Nov. 2, 2022.
2. Lamb J, Bowden T. The history of contact lenses. Contact lenses: Butterworth Heinemann Elsevier; 2007:1-20.
3. Cope JR, Collier SA, Nethercut N, Jones JM, Yates K, Yoder JS. Risk Behaviors for Contact Lens-Related Eye Infections Among Adults and Adolescents - United States, 2016. MMWR Morb Mortality Wkly Rep. 2017 Aug 18;66:841-845.
4. Nichols JJ, Willcox MD, Bron AJ, et al; members of the TFOS International Workshop on Contact Lens Discomfort. The TFOS International Workshop on Contact Lens Discomfort: executive summary. Invest Ophthalmol Vis Sci. 2013 Oct;54:TFOS7-TFOS13.
5. U.S. Food and Drug Administration (FDA). Premarket Approval N16895: Soflens Contact Lenses (Polymacon). 1971 Mar 18.
6. Grant NJ, Fujimoto MJ, Caroline PJ, Norman CW. History of contact lenses: A timeline celebrating the 50th anniversary of soft contact lenses. Contact Lens Spectrum (Special Edition). 2021;36:52-54.
7. Mondino BJ, Salamon SM, Zaidman GW. Allergic and toxic reactions of soft contact lens wearers. Surv Ophthalmol. 1982 May-Jun;26:337-344.
8. Stone R, Mowrey-Mckee M, Kreutzer P. Protein: source of lens discoloration. Contact Lens Forum. 1984;9:33.
9. Stone RP. Why Contact Lens Groups, Contact Lens Spectrum. 1988;3:38-41.
10. International Organization for Standardization. Ophthalmic optics — Contact lenses — Part 1: Vocabulary, classification system and recommendations for labelling specifications. 2017. Available at iso.org/standard/66338.html . Accessed Oct. 28, 2022.
11. Stone RP. Lens Groups and Lens Care. J Jpn Contact Lens Soc. 1997;39:32-38.
12. Nalley C. Material gains: 50 years of the soft contact lens. Rev Cornea Contact Lens. 2021 Apr;10-14.
13. Holden BA, Mertz GW. Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci. 1984 Oct;25:1161-1167.
14. Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J. 2002 Jan;28:12-27.
15. FDA. Premarket Approval P850068: Silsoft (Elastofilcon A) Contact Lenses. 1985 Dec 31.
16. Jones L, Mann A, Evans K, Tighe B. An in vivo comparison of the kinetics of protein and lipid deposition on group II and group IV frequent-replacement contact lenses. Optom Vis Sci. 2000 Oct;77(10):503-10.
17. Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology. 2008 Oct;115:1655-1662.
18. CDC. Healthy Contact Lens Wear and Care; Water and Contact lenses don’t mix. Reviewed 2021 May 28.
19. Chou B. The evolution of silicone hydrogel lenses. Contact Lens Spectrum. 2008 Jun;23:37-39.
20. Mueller KF, Kleiner EK. Crosslinked, addition monomer or polymer. Google Patents #US4136250A. Available at patents.google.com/patent/US4136250 . Accessed Oct. 28, 2022.
21. Tanaka K, Takahashi K, Kanada M, et al. Copolymer for soft contact lens, its preparation and soft contact lens made therefrom. 1979; US4139513. Available at patents.google.com/patent/US4139513A . Accessed Oct. 28, 2022.
22. Deichart WG, Su KC, Buren M. Polysiloxane composition and contact lens. 1979; US4153641. Available at patents.google.com/patent/US4153641A/en?oq=US4153641 . Accessed Oct. 28, 2022.
23. Szczotka-Flynn L. Looking at silicone hydrogels across generations. Optometric Management. 2008 May 1.
24. FDA. Premarket Approval K970746: lotrafilcon A. 1997 May 9.
25. FDA. Premarket Approval P980006/S004: Pure Vision™ (balafilcon A) Visibility Tinted Contact Lenses. 2001 Nov 20.
26. FDA. Premarket Approval P980006: Pure Vision Visibility Tinted Contact Lens for Extended Wear. 1999 Feb 5.
27. FDA. 510(k) Premarket Approval K032340: Vistakon (galyfilcon A) Soft Contact Lens. 2008 Oct. 16.
28. FDA. Premarket Approval P080011: Biofinity (Comfilcon A). 2008 Nov 19.
29. Stone RP. A New Perspective for Lens Care Classifying Silicone Hydrogels [Internet]. 2007. Available at http://www.siliconehydrogels.org/editorials/jun_07.asp
30. Hutter JC. FDA Group V: Is a Single Grouping Sufficient to Describe SiH Performance? Silicone Hydrogels. 2007 Nov. Available at http://www.siliconehydrogels.org/editorials/nov_07.asp . Accessed Oct. 28, 2022.
31. Thekveli S, Qui Y, Kapoor Y, Liang W, Pruitt J. Structure property relationship of delefilcon A lenses. Cont Lens Anterior Eye. 2012 Dec 1;35(Suppl 1):E14.
32. Alcon. Dailies Total1 contact lenses product information. 2012.
33. FDA. 510(d) Premarket approval. Total30 brand soft contact lenses. 2021 Apr 12.
34. Alcon. Total30 Product information. 2022. Available at myalcon.com/professional/contact-lenses/monthly/total30 . Accessed Nov. 1, 2022.
35. Ishihara K, Papas E, Pruitt J, et al. Optimizing the water gradient lens with a biomimetic surface enhancement. Contact Lens Spectrum (supplement). 2021 May:21.
36. Gulmiri A, Liao J, McNaughton L. 2022 Contact Lenses and Solutions Summary. Contact Lens Spectrum (supplement). 2022 Sep. Available at clspectrum.com/resources/class-pdfs/0922-class_final_hyperlinks . Accessed Oct. 28, 2022.
37. Dumbleton KA, Woods CA, Jones LW, Fonn D. The relationship between compliance with lens replacement and contact lens-related problems in silicone hydrogel wearers. Cont Lens Anterior Eye. 2011 Oct;34:216-222.