FDA Group V: Is a Single Grouping Sufficient to Describe SiH Performance?

Joseph C. Hutter, Ph.D., Center for Devices and Radiological Health, Food and Drug Administration Joe Hutter is currently a reviewer in the Division of Ophthalmic and Ear, Nose, and Throat Devices, where he is responsible for the review of contact lens materials and care product solution chemistry for safety and effectiveness.  He graduated from the University of Florida, BSChE, and Pennsylvania State University, MS and PhD, all in chemical engineering.

The FDA groupings for contact lens materials were initially developed to categorize their behavior in different care product solutions and interaction with protein from the tear film. [1, 2] Currently there are four groups based on differences in water content and ionic charge. [1]  These groupings have been historically successful in describing material interactions with proteins and in minimizing solution incompatibilities for conventional poly(2-hydroxyethyl methacrylate)-based hydrogels when exposed to various lens care solutions. 

The introduction of silicone hydrogel materials saw them being placed into one of these existing four groups.  Most of the lenses were placed into the FDA group I category (low water content, nonionic), with one material (balafilcon A) being assigned to the FDA group III category (low water content, ionic).  Relatively soon after these lenses came into use, solution/lens interactions resulting in corneal staining were identified. [3, 4]  Also, lens dimensional stability was affected despite established care product compatibility with conventional poly(2-hydroxyethyl methacrylate) lenses in the same FDA group. [5]  In addition, the depletion of preservatives such as alexidine from the solution in the lens case by either absorption or adsorption to the lens material were reported. [6]  This latter point is important as this may reduce disinfection effectiveness, due to less disinfectant being available for microbial disinfection.  Recently, the International Standards Organization (ISO) has recognized that silicone hydrogels do not effectively “fit” within the existing FDA materials grouping and that a further “group V” category should be added for this class of high oxygen permeability hydrogel materials. 

Although the addition of an FDA group V is a step in the right direction, a single category may not adequately differentiate lens characteristics or predict care product interactions. The interaction of any hydrogel contact lens with any specific solution component depends on many factors, including pore size of the material, molecular weight (or size) of the component in question, ionic content (or charge) of lens material and the solution component, hydrophobicity of either element, and surface treatment of the material. Water content generally correlates with material pore size, and ionic content of the material will influence the adsorption of any charged species, including those in the tears (e.g. proteins) and in the disinfecting solution, including surfactants, chelating agents and preservatives. 

It is clear from these points that the interaction of care product components with hydrogel materials is related to at least two and possibly more distinct factors.  First, the size of the water filled pores in the lens material will limit the size of the molecule in tears or care product solutions that can penetrate the lens material.  Second, the electrostatic interactions between the charge of the material and the charge of the molecule may cause selective attraction or repulsion.  Both of the above mechanisms (pore size and ionic content or charge) are important factors to consider when investigating the behavior of new silicone hydrogel materials.  In addition, the presence of more hydrophobic phases and surface treatments [7-12] add additional complexities to silicone hydrogel lens - solution interactions, that were not present to any large extent with conventional materials. 

Any new FDA group for silicone hydrogel materials will need to account for the marked differences in surface and bulk properties of these materials, which affect adsorption, absorption and transport rates of molecules.  Oxygen transfer in silicone hydrogels occurs mostly through the hydrophobic silicone phase, although some transfer does occur in the water-filled pores.  This hydrophobic phase does not interact with many of the hydrophilic components in the care product solution, but will attract lipids and other hydrophobic molecules.  Oxygen transfer through a typical silicone polymer phase is likely occurring by a solution-diffusion mechanism. [13]  In this mechanism, hydrodynamic flow cannot occur because of a barrier.  As gases move through the membrane, polymer segments move out of the way, creating holes into which the gas can diffuse.  This mechanism results in a permeability which depends on both gas solubility in the polymer, as well as diffusivity of the gas in the polymer.  In general, a form of Fick’s Law for diffusion would work well to model this process and the resulting gas flux is driven by partial pressure.  The diffusion is temperature sensitive, since molecular motion of polymer segments is temperature sensitive. 

In the water filled pores, either a sieve mechanism [13], or Maxwell-Stefan model (solution – diffusion model) would be more appropriate. [14]  Hydrophilic molecules such as preservatives, surfactants, buffers, and ions, would likely transport through the lens by this type of mechanism.  This type of mechanism also applies to transport through conventional poly(2-hydroxyethyl methacrylate) materials. 

Proteins in solution, such as lysozyme, have a positive charge in care product solutions at neutral pH (isoelectric point pI about 10).  If the lens contains an acidic monomer (such as methacrylic acid), this will create an overall net negative charge in the lens matrix, which  will attract positively charged species such as lysozyme, along with several common preservatives such as PHMB.  It is thus clear that in addition to pore size or water content, ionic charge of the lens matrix will determine how it will interact with certain solution components.  The observed high protein absorption of FDA group 4 lenses is due to a combination of high pore size (water content) and ionic charge. [15, 16]

A unique characteristic to most silicone hydrogel materials is the presence of a surface treatment or modification, [1, 7, 17] which may be a feature that controls how the lens interacts with certain solution components, regardless of the chemistry of the lens matrix or “bulk”.  When silicone is added to the hydrogel material, the hydrophobic domains lower the surface energy of the lens, making it significantly less wettable and comfortable.  These surface treatments or modifications make the surfaces of silicone hydrogel materials more hydrophilic.  Surface treatments can function to isolate pores (such as that seen in lotrafilcon A and lotrafilcon B), or add hydrophilic high surface energy sites that are dispersed on the lens surface (such as that seen in the case of balafilcon A). [11]  If the pores of a lens are blocked by a uniform surface treatment, such as that seen in the lotrafilcon A and lotrafilcon B materials, much less material is likely to penetrate into the lens interior.  This may help to explain the low protein deposition that occurs with these materials. [18, 19] 

At the current time, insufficient data are available to sort out all of these potential effects and the relative importance of each.  As more silicone hydrogel contact lenses come on the market, it is becoming more and more difficult to predict potential solution incompatibilities, unless each generic lens material is tested with each care product. 

A definitive silicone hydrogel grouping system will help predict care product interactions with these novel materials and hopefully avoid the scenario in which compatible contact lenses would need to be listed on a lens care product’s label.  It is likely that group V subcategories will be defined to better predict lens-solution incompatibilities.

The next article in this series will discuss the importance of preservative concentration in lens cases.

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