Document ppp97mVd006e2q6VgpOjvamjE
IMPACT ASSESSMENT and ANALYSIS OF ALTERNATIVES for the potential restriction of the per and polyfluoroalkyl substances (PFAS) used in rigid gas permeable (RGP) contact lenses
SUBSTANCES: Per and polyfluoroalkyl substances (PFAS) FROM: Menicon B.V. USE: Rigid gas permeable (RGP) contact lenses DATE: 27 07 2023
PREPARED BY: EPPA SA/NV
Place du Luxembourg 2 1050 Brussels, Belgium EU transparency register: 3136750124992
PUBLIC VERSION
Impact Assessment and Analysis of Alternatives | PFAS | EU REACH
Table of Contents
1. EXECUTIVE SUMMARY
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2. AIMS AND SCOPE OF THE IMPACT ASSESSMENT
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2.1 THE PFAS RESTRICTION PROPOSAL: CONTEXT AND REGULATORY CONSIDERATIONS
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2.2 METHODOLOGY
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2.3 MENICON
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2.4 OVERVIEW OF RIGID GAS PERMEABLE CONTACT LENSES AND LENS CARE PRODUCTS
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2.4.1 QUANTITY OF RGP CONTACT LENSES AND LCPS SOLD AND SHIPPED IN THE EEA BY MENICON
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2.5 OVERVIEW OF THE RIGID GAS PERMEABLE CONTACT LENS SUPPLY CHAIN
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2.5.1 THE MANUFACTURING PROCESS OF RGP CONTACT LENSES
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3. ANALYSIS OF ALTERNATIVES
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3.1 TISILFOCON A
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3.2 RGP LENS USES
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3.2.1 IRREGULAR ASTIGMATISM
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3.3 PFASCONTAINING PRODUCTS
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3.3.1 MENICON Z LENS MATERIAL
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3.3.2 ANNUAL VOLUME OF PFAS USED
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3.3.3 RGP LENS MATERIAL: R&D PROCESS
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3.3 AI (ARTIFICIAL INTELLIGENCE) SEARCH
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3.4 ASSESSMENT OF SHORTLISTED ALTERNATIVES
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3.4.1 ALTERNATIVE 1: SILICONE BASED SUBSTANCES
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3.4.2 ALTERNATIVE 2: SILICONE NANOPARTICLES
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3.4.3 ALTERNATIVE 3: TITANIUM NANOPARTICLES
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3.4. ALTERNATIVE 4: CHITOSAN
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3.4.5 CONCLUSION ON SHORTLISTED ALTERNATIVES
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4. ECONOMIC AND SOCIAL IMPACTS
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4.1 ECONOMIC IMPACTS
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4.1.1 QUANTITY OF PFAS USED IN RIGID GAS PERMEABLE CONTACT LENSES AND WASTE MANAGEMENT
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4.1.2 BUSINESS IMPACTS ON MANUFACTURERS OF RIGID GAS PERMEABLE CONTACT LENSES
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4.1.3 MARKET IMPACTS
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4.2 SOCIAL IMPACTS
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4.2.1 IMPACTS ON UNEMPLOYMENT
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4.2.2 IMPACTS ON RGP CONTACT LENS USERS
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5. CONCLUSION
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C O N F I D E N T I A L
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Impact Assessment and Analysis of Alternatives | PFAS | EU REACH
ANNEX I - LIST OF STANDARDS AND REGULATIONS APPLICABLE TO RGP CONTACT LENSES AND
PRODUCTS TARGETED BY THE POTENTIAL PFAS RESTRICTION
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MEDICAL DEVICES DIRECTIVE
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QUALITY MANAGEMENT SYSTEM
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RISK MANAGEMENT
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MEDDEV'S
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INCOMING INSPECTION
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CLINICAL EVALUATION / CLINICAL INVESTIGATION
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LABELING AND INFORMATION
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SHELF LIFE
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CONTACT LENSES GENERAL
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COMPATIBILITY OF CONTACT LENSES
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BIOLOGICAL EVALUATION
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TRIAL LENSES
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STERILITY
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CLEANROOMS
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VIGILANCE
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USABILITY
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INTERNAL AUDITS
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ANNEX II - OVERVIEW OF THE KEY STUDIES ON GASPERMEABILITY IN CONTACT LENSES
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ANNEX III - OVERVIEW OF THE KEY STUDIES ON THE USE OF CONVENTIONAL RGP LENSES AND
SCLERAL RGP LENSES IN PATIENTS WITH CORNEAL ISSUES
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Impact Assessment and Analysis of Alternatives | PFAS | EU REACH
Abbreviations
AI: Artificial Intelligence CAGR: Compound Annual Growth Rate CAR: Competent Authority Report CAs: Competent Authorities CLs: Contact Lenses DLS: Dynamic Light Scattering Dk: Oxygen Permeability Dpt: Diopter EBIT: Earnings Before Interest and Taxes EC: European Commission ECHA: European Chemicals Agency EEA: European Economic Area EU: European Union EUR: Euro (currency) EWP: Equilibrium Water Content GWP: Global Warming Potential IP: Intellectual Property j: Oxygen Flux LCPs: Lens Care Products LRTP: LongRange Transport Potential NPV: Net Present Value OECD: Organization for Economic Co operation and Development OrthoK: Orthokeratology MTO: MadeToOrder NLP: Natural Language Processing PMT: Persistent, Mobile and Toxic PFAS: Per and Polyfluoroalkyl Substances QOL: Quality of Life QOV: Quality of Vision RAC: Committee for Risk Assessment
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REACH: Registration, Evaluation, Authorisation and Restriction of Chemicals RAs: Registration Authorities RGP: Rigid Gas Permeable R&D: Research and Development SA: Silicone Acrylate SEAC: Committee for SocioEconomic Analysis SEM: Scanning Electron Microscope SVHC: Substance of Very High Concern TEM: Transmission Electron Microscope vPvM: very Persistent and very Mobile
Impact Assessment and Analysis of Alternatives | PFAS | EU REACH
List of Tables
Table 1: Key technical characteristics of RGP lens materials available on the market
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Table 2: AI Search Phase I
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Table 3: AI Search Phase II
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Table 4: AI Search Phase III
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Table 5: Shortlisted alternatives
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Table 6: Duration of unemployment in EU-27
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List of Figures
Figure 1: The global supply chain of RGP contact lenses
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Figure 2: The manufacturing process of RGP raw contact lenses material
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Figure 3: A comparison of material versus lens production
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Figure 4: The carving of an RGP lens
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Figure 5: Tisilfocon
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Figure 6: An overview of the most important physical properties of a contact lens
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Figure 7: Shore hardness scales
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Figure 8: An advanced case of keratoconus
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Figure 9: Maturity radar
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Impact Assessment and Analysis of Alternatives | PFAS | EU REACH
1. Executive Summary
Purpose
On 13 January 2023, the Competent Authorities (CAs) of the Netherlands, Germany, Sweden, Denmark, and Norway submitted a joint proposal to ECHA for a broad restriction under REACH of a group of fluorinated substances, namely PFAS (Per and Polyfluoroalkyl Substances). PFAS is a group of more than 10,000 synthetic (i.e., manmade) chemicals that are ingredients in various consumer and industrial products. The use of PFAS is prevalent in the rigid gas permeable (RGP) contact lens industry.1
This report focuses on the social and economic impacts on the European market of the potential PFAS restriction based on a large manufacturer of RGP contact lenses. It also briefly considers the impact on RGP contact lens wearers in a qualitative manner. It has been performed by EPPA2 at the request of Menicon, in view of providing regulators with strong evidencebased findings on the expected social and economic impacts that are expected to occur should these substances be restricted under REACH. The report also includes the analysis of alternatives, which discusses the technical performance of PFAS in RGP contact lenses and highlights the lack of technically suitable alternatives.
Menicon is positioned as an industry leader and pioneer in contact lens production. The company's main business areas are contact lenses, contact lens care products (LCPs), medical instruments and supplies, and intraocular lenses. This assessment evaluates the impacts of a potential PFAS restriction from Menicon's entities that are located within the EEA, namely in the Netherlands, France, Germany, Italy, and Spain. As noted below, a potential PFAS restriction would affect the distribution of Menicon's goods and would therefore also affect Menicon's distributors and downstream customers, which are also located in the EEA.
Methodology
The assessment of the social and economic impacts in this report has been conducted in accordance with the existing official guidance from ECHA under REACH.3 It is based on information and data gathered from Menicon, a manufacturer of RGP contact lenses that uses PFAS, covering a market
1 Gas permeable contact lenses are rigid lenses that allow oxygen to pass through the lens. They are also called GP lenses, rigid gas permeable lenses, RGP lenses and oxygen permeable lenses. RGP lenses are special because they are made from a firm and durable plastic material, which allows them to retain their shape and ensure sharp vision. 2 www.eppa.com 3 The ECHA Guideline for an ECHA Guidance for an SEA for the restriction proposals is available at: https://echa.europa.eu/documents/10162/23036412/sea_restrictions_en.pdf/2d7c8e06b5dd40fcb646 3467b5082a9d
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share of approximately 40% of the EEA RGP contact lens market. The market share of 40% is a high level estimation based on approximations made by industry professionals; there is no data available about the size of the niche RGP contact lens market. Based on this, we conservatively decide to not use this percentage to extrapolate the economic and social impacts to the EEA market.
This impact assessment gathers economic information to describe, in both qualitative and quantitative terms, the (order of magnitude of) social and economic impacts on the EEA RGP contact lens industry and society are expected to face from the ban of PFAS. The report also covers the analysis of alternatives which highlights the lack of technically suitable alternatives, as well as the technical difficulties associated with the substitution of PFAS via alternatives.
The assessments presented in this report are as close to real data or to perception of future changes as possible to have conservative estimates, always putting the protection of human health and the environment upfront.
Main findings
Menicon, founded in 1951, is positioned as an industry leader and pioneer in contact lens production. The company's main business areas are contact lenses, LCPs, medical instruments and supplies, and intraocular lenses. Menicon is the only manufacturer in the world that is dedicated to all areas of the contact lens industry, encompassing research and development, material development, lens design, and the manufacturing of contact lenses and care solutions. The company also engages in the marketing, sales, distribution, import, and export of contact lenses and other medical products. Menicon's entities in the EEA are located in the Netherlands, France, Germany, Italy, and Spain.
Menicon uses PFAS to manufacture RGP contact lenses in the EU. PFAS are present as a raw material and as a part of a mixture intended for polymerisation used for manufacturing RGP lenses. The proposed PFAS restriction would consequently affect RGP contact lenses and RGP LCPs. PFAS are not used in any other products made by Menicon, and have no other part in the manufacturing processes. The primary functions of PFAS in RGP contact lenses are to secure oxygen permeability of the finished product and to protect it from fouling. Other critical functions include surface characteristics/wettability and hardness.
In Menicon's experience, it takes from 10 to 13 years to place a new RGP product on the market if it is based on a new combination of PFAS compounds and silicone compounds (new lens material). The usual steps include the development of a new mixture (with accompanying testing and validation stages), lens design, manufacturing process testing validation stages, biosafety certification, clinical study, shelflife determination, and market approval. However, all the RGP projects accomplished by Menicon up to now have been based on availability of fluorinated compounds. If there is no derogation for PFAS use in RGP contact lenses, it is difficult to predict how long a quest for substitution will take. Evidently, it will be more than 13 years we currently need.
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Menicon asked FINDEST, a company specialized in AIenabled technologies/innovations scouting, to conduct an artificial intelligence (AI) study, with the goal to identify potential alternatives. The goal of the AI study was to identify alternative materials based on key material requirements of the PFAS compound. The AI scouting procedure was designed so as not to overlook any potential substitute, be it substance, additive, component, technology, or combination of the previously mentioned.
The analysis of alternatives concludes that no viable substitute is available now or will be available in the foreseeable future. The AI search specially designed to explore all available scientific literature and patents for a possible substitution did not reveal newly appeared options which would be worth investigating at the current stage.
As a consequence, in the most likely "nonuse" scenario, Menicon will have no other option but to halt the production and imports of RGP lenses in the EEA. This is because the PFAS used are integral components for the lens blanks that are used to manufacture RGP contact lenses. The market for RGP contact lenses will therefore become minimal and have no prospects for the future as a consequence of a PFAS ban.
A potential broad restriction would have disproportionate socioeconomic implications on the EEA RGP contact lens industry. In the restriction scenario, Menicon would shift its focus fully on madeto order soft lenses and disposable lenses instead. Overall, the total impact of a PFAS restriction is monetised as more than 50 M EUR for Menicon, including 5 to 10 M EUR of social impacts from unemployment in the EEA, 5 to 10 M EUR of substitution costs, and 30 to 40 M EUR of economic impacts (EBIT loss). This is a conservative estimate (lower bound), based on the understanding that this is not the sole injury likely to be suffered in the EEA. The market share covered by this impact assessment is approximately 40% of the whole EEA RGP contact lens market. The market share of 40% is a highlevel estimation based on approximations made by industry professionals; there is no data available about the size of the niche RGP contact lens market. Based on this, we conservatively decide to not use this percentage to extrapolate the economic and social impacts to the EEA market.
A potential PFAS restriction would affect the distribution of Menicon's goods and would therefore also affect Menicon's distributors and downstream customers, which are located in other EEA countries. Menicon's entities in the EEA have 20,000 to 25,000 downstream customers that purchase RGP contact lenses (containing PFAS) or LCPs for RGP contact lenses. These downstream users include online retailers and optical stores, as well as eye care practitioners, opticians, and optometrists. In the restriction scenario, Menicon's distributors would also fully focus on madetoorder soft lenses and disposable lenses. In addition, there would likely be a negative impact on investments in R&D and on the competitiveness of the RGP contact lens market in the EEA.
The qualityoflife reductions for RGP contact lens users would be large in case of a potential PFAS restriction. A large group of RGP contact lens users with specific medical and eye conditions, such as myopia, hyperopia, presbyopia, and astigmatism, would be adversely
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affected in case of a potential PFAS restriction. A large group of current users cannot switch to alternatives such as soft lenses because they do not sufficiently correct visual acuity.
Based on the evidencebased considerations below, the impact assessment and analysis of alternatives performed conclude that a broad restriction for the use of PFAS in rigid gas permeable (RGP) contact lenses will have disproportionate negative impacts on the European economy and society, as well as on the qualityoflife of RGP contact lens users. The analysis presented in this report reasonably justifies the request for a timeunlimited derogation for the use of critical PFAS in RGP contact lenses.
2. Aims and Scope of the Impact Assessment
2.1 The PFAS restriction proposal: context and regulatory considerations
On 13 January 2023, the Competent Authorities (CAs) of the Netherlands, Germany, Sweden, Denmark, and Norway submitted a joint REACH restriction proposal for a broad group of fluorinated substances in Annex XVII of REACH, to limit the risks to the environment and human health from the manufacture and use of a wide range of PFAS. It is based on the persistent/very persistent (P/vP) criteria according to REACH Annex XIII and the inability to degrade under environmental conditions. All PFAS in scope of this restriction proposal are either persistent themselves or degrade to other persistent PFAS. Additionally, supporting concerns emphasised by ECHA are mobility (M) of compounds, resulting in potential (bio)accumulation and toxicity in animals, as well as longrange transport potential (LRTP), accumulation in plants, and global warming potential (GWP). The opinion making phase at ECHA takes 12 to 15 months. After this, the proposal, and the opinions of RAC and SEAC are forwarded to the European Commission (EC) for decisionmaking by the EC with the Member States (the entry into force of a potential restriction is anticipated to take place in 2025 and become effective in 2026/2027).
In the proposed restriction, PFAS are defined as any substance containing at least one fully fluorinated methyl (CF3) or methylene (CF2) carbon atom (without any hydrogen, chlorine, bromine, or iodine attached to it). The definition is based on the OECD definition of PFAS published in 2021 and covers over 10,000 PFAS, including some fully degradable subgroups. In May 2017, the German authorities proposed criteria for identifying such chemicals in the regulatory context of EU REACH Regulation (EC) No 1907/2006. Substances meeting these criteria are referred to as either persistent, mobile, and toxic (PMT) or very persistent and very mobile (vPvM) substances. Recently, the EC has published a Delegated Regulation amending CLP Regulation, which sets out new hazard classes and criteria for the classification, including of PMT and vPvM substances and mixtures. 4
4 COMMISSION DELEGATED REGULATION (EU) 2023/707 of 19 December 2022 amending Regulation (EC) No 1272/2008 as regards hazard classes and criteria for the classification, labelling and packaging of substances and mixtures (OJ, 31/03/2023, L 93/7).
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Many PFAS are efficient surfactants or surface protectors because of the perfluoroalkyl moiety's high chemical and thermal stability as well as its ability to repel water and oil. As a result, they have been produced in large quantities and used in a variety of industrial, commercial, and consumer applications since the late 1940s.5, 6, 7
Certain members of the PFAS chemical family have already been (or are currently in the process of being) restricted under REACH: PFOA, PFHxA, PFHxS, C9C14 PFCA. Other members of the group are under authorisation procedures (HFPODA, PFDA, PFNA), or recognised as a Substance of Very High Concern (SVHC) (PFBS). Measures on certain members of the PFAS group are in place also under the POPs Regulation, Food Contact materials legislation, new Drinking Water legislation and FGas Regulation. The aim of the broad restriction is to move away from this "piecemeal approach", which has led to "regrettable substitution" of restricted substances by other members of the PFAS chemical family.
2.2 Methodology
This impact assessment aims to identify and to assess in both qualitative and quantitative terms the socioeconomic impacts that are expected to occur in case of a REACH restriction to this group of substances. The impact assessment covers the use of PFAS in RGP contact lenses.
The market share covered by this impact assessment is approximated to be 40% of the EEA RGP contact lens industry. The estimates reported in this impact assessment should be considered as a minimum (lower bound) of the expected impacts of a PFAS restriction for European manufacturers of RGP contact lenses produced with PFAS.
From a geographical perspective, this analysis focuses on the European Economic Area (EEA) territory, consisting of the European Union (EU27), Iceland, Liechtenstein, and Norway. For the purposes of estimating economic impacts, it has been decided to use a 4year time horizon, which is the time period suggested by SEAC when there is no alternative available in general (SAGA).8, 9
5 Banks, R.E., Smart, B.E., Tatlow, J.C., 1994. Organofluorine chemistry: Principles and commercial applications. New York (NY): Plenum. 670 p. ISBN 9781489912022.
6 Kissa, E., 2001. Fluorinated Surfactants and Repellents, 2nd Edition, CRC Press. ISBN 9780824704728.
7 Buck, R.C., Franklin, J., Berger, U., Conder, J.M., Cousins, I.T., de Voogt, P., Jensen, A.A., Kannan, K., Mabury, S.A., van Leeuwen, S.P., 2011. Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins. Integr. Environ. Assess. Manag. 7, 513-541.
8 European Commission, 2020. Assessment of alternatives: Suitable alternative available in general & requirement for a substitution plan. Available at: https://echa.europa.eu/documents/10162/13637/ec_note_suitable_alternative_in_general.pdf/5d0f551b 92b531578fdff2507cf071c1
9 ECHA, 2021. SEAC's approach to assessing changes in producer surplus. Available at: https://echa.europa.eu/documents/10162/0/afa_seac_surplusloss_seac52_en.pdf/5e24c796d6fad8cc 882cdf887c6cf6be?t=1633422139138
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In other terms, the impact assessment accounts for the costs to the EEA society in the event PFAS substances are prohibited from being manufactured, used, and placed on the market, and/or for the socioeconomic costs of a complete ban (REACH restriction) starting from the year 2027 (year of the entry into force of the proposed restriction plus 18 months of transition period).
Future monetary values have been estimated by using the concept of net present value (NPV), adopting a 3% annual discount rate, which is the standard discount rate adopted by the European Commission and European agencies (e.g., ECHA) in impact assessments.10 All monetised values have been adjusted to a base year, assumed to be 2027. Information and data have been aggregated and anonymised. Statements and estimations from the participating company are as close to real data or to perception of future changes as possible.
The assessment has been conducted in accordance with the existing official guidance from ECHA under REACH. ECHA has developed a solid methodology for monetising economic and social impacts in the context of the REACH Regulation, with the support of a dedicated committee (SEAC). More specifically, the methodologies for monetising economic and social impacts in this report is consistently applied for REACH applications for authorisation of SVHC, and REACH restrictions, with a view of forecasting the impacts of different regulatory options.
2.3 Menicon
Menicon, founded in 1951, is positioned as an industry leader and pioneer in contact lens production. The company's main business areas are contact lenses, contact lens care products, medical instruments and supplies, and intraocular lenses. Menicon is the only manufacturer in the world that is dedicated to all areas of the contact lens industry, encompassing research and development, material development, lens design, and the manufacturing of contact lenses and care solutions. The company also engages in the marketing, sales, distribution, import, and export of contact lenses and other medical products. Menicon's products, which includes disposable contact lenses, RGP contact lenses, and lens care products (LCPs), etc., are distributed in more than 80 countries.
Menicon has numerous affiliated companies that are located within the EEA. The social and economic impacts in this impact assessment consider the impacts from Menicon's entities that are located within the EEA, namely in the Netherlands (Menicon Holdings B.V. and Menicon B.V.), France (Menicon SAS and Menicon Pharma SAS), Germany (Menicon GmbH), Italy (SOLEKO S.p.A), and Spain (Menicon Iberia S.L.).
The overall company revenue in the EEA in the fiscal year 20212022 was 70 to 75 M EUR.11 RGP contact lenses and RGP LCPs account for approximately 50% to 60% of the overall revenue. Menicon employs 501 employees within the EEA, 75 to 100 of which are directly related to RGP contact lenses
10 European Commission, 2021. Better Regulation Guidelines and Toolbox. https://commission.europa.eu/document/download/9c8d21898abd4f2984e9 abc843cc68e0_en?filename=br_toolboxnov_2021_en.pdf
11 Using the average ECB exchange rate between 1 April 2021 to 31 March 2022 (1 EUR = 130.53 JPY) based on [CONF.] JPY.
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and RGP LCPs. The employees that are directly related to RGP contact lenses and RGP LCPs are either engaged in the production of these products or are supporting staff.
Standards and regulations applicable to Menicon's business
Annex I of this report provides a comprehensive overview of all standards and regulations applicable to RGP contact lenses and all products targeted by the potential PFAS restriction, ranging from those targeting medical devices and biological evaluation to risk management and shelflife.
2.4 Overview of rigid gas permeable contact lenses and lens care products
Rigid gas permeable (RGP) contact lenses
Menicon reported that all RGP contact lens design families would be affected in case of a restriction. A lens design family consists of multiple lens modalities for specific eye conditions (e.g., myopia, hyperopia, presbyopia, astigmatism) and medical conditions or combinations of the aforementioned conditions. A nonexhaustive list of examples of RGP contact lenses, that are manufactured and placed on the market by Menicon, is provided below:
Corneal contact lenses; (Mini and full) scleral contact lenses; Daytime contact lenses; Orthokeratology contact lenses.
Lens care products (LCPs)
Menicon further reported that accompanying LCPs with varying functions would also be affected in case of a PFAS restriction. LCPs are essential and indispensable products for the successful use of RGP lenses. Therefore, in the event that RGPs would not be able to stay on the market due to the PFAS restriction, LCPs specifically designed for RGPs would face a significant risk of disappearance as well. A nonexhaustive list of examples of LCPs, that are manufactured and placed on the market by Menicon, is provided below:
Cleaning solutions and sprays to remove proteins and dirt and to disinfect, for example, hydrogen peroxide solutions
Other solutions with differing or multiple purposes for endconsumers and practitioners. Examples of these purposes include rinsing, soaking, cleaning, conditioning, maintaining/enhancing wettability, maintaining/enhancing comfort, disinfecting, preserving, diluting, and storing
Products for myopia correction, control, and management Products for irregular corneas Starter and travel kits Cases and boxes Suction cups Holders Vials.
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2.4.1 Quantity of RGP contact lenses and LCPs sold and shipped in the EEA by Menicon A total of 400,000 to 600,000 PFAScontaining RGP contact lenses were shipped in the EEA market in 2022 by Menicon's entities in the Netherlands, France, and Italy. These include corneal and (mini and full) scleral lenses. In 2022, Menicon's turnover from the total sales of RGP contact lenses was 25 to 30 M EUR in 2022 and the turnover from the total sales of RGP LCPs was 15 to 25 M EUR in the same year. This amounts to a total turnover from the total sales of 40 to 55 M EUR for these products in 2022.
2.5 Overview of the rigid gas permeable contact lens supply chain
The global supply chain of RGP contact lenses is illustrated in Figure 1 below. Menicon's role in this supply chain encompasses supplying the material, manufacturing RGP contact lenses, and distributing RGP contact lenses.
Figure 1: The global supply chain of RGP contact lenses.
Material supply
Lens manufacturing
Distribution
Retail
Enduser
The steps of this supply chain are described below:
1. Material supply: the materials (polymers) that are used to manufacture RGP contact lenses are produced and supplied. The polymers that contain PFAS are lens blanks (also called buttons). The blanks are manufactured in Japan and are then exported to Menicon's subsidiaries and labs in the EEA.
2. Lens manufacturing: lens manufactures utilise the sourced materials to produce RGP contact lenses. See `the manufacturing process of RGP contact lenses' (section 2.5.1).
3. Distribution: the RGP contact lenses are distributed to downstream retailers.
4. Retail: endusers can purchase RGP contact lenses. The retailers in the EEA include online retailers, optical stores, etc.
5. End user: users wear RGP contact lenses for various reasons, including but not limited to vision correction and eye condition treatment. See `impacts on contact lens users' (section 4.2.2).
2.5.1 The manufacturing process of RGP contact lenses
This section describes the manufacturing process of RGP contact lenses, and the role of PFAS in this process. The manufacturing process of RGP contact lenses is illustrated in Figure 2 and is described below. RGP contact lenses are manufactured in the Netherlands and France. RGP LCPs are manufactured in France and Italy.
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Figure 2: The manufacturing process of RGP raw contact lenses material.
Globally, Menicon only uses PFAS as a raw material for lens blanks (also called buttons). Lens blanks are manufactured outside the EU. There are no other PFAS used in any other process. As illustrated In Figure 2, after raw materials pass the relevant inspection, PFAS and other materials are used in mixing and consequently in polymerisation. During polymerisation, PFAS monomers are polymerised with other materials to generate solid polymer rods. These rods are consequently lathed down into polymer lens blanks. Lens blanks are subsequently used to produce the finished RGP contact lens. The steps involved in cutting and lathing lens blanks into lenses are as follows:
1. Raw material precut lens blank is lathed to create the back surface of the lens 2. Backsurface polishing 3. Blocking/gluing on a new carrier (mounting base) 4. Front surface lathing 5. Laser engraving unique identifier 6. Front surface polishing 7. Deblocking from carrier/mounting base 8. Inspection of all ISO specifications 9. Oxygen vacuum plasma surface treatment 10. Soaking in packaging/shipping solutions (disinfectant) 11. Packaging in blister case and sealed by aluminium seal.
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In summary, liquid monomers are used to produce solid polymer rods. Solid polymer rods are subsequently used to produce polymer lens blanks. Polymer lens blanks are subsequently used to produce the finished RGP contact lens.
3. Analysis of Alternatives
Menicon uses fluorinated polymers Tisilfocon A and Tolofocon A to manufacture rigid gas permeable contact lenses. 12 PFAS are present in the material used for manufacturing RGP lenses, and, consequently, in these lenses. PFAS are not used in any other products made by Menicon, and have no other part in the manufacturing processes.
The specific fluorinated monomers polymerised to produce a matrix are: HFPM (hexafluoroisopropyl methacrylate) TFEM (trifluoroethyl methacrylate) BHI (Bishexafluoroisopropyl itaconate)
All these monomers are liquids that are manufactured outside the EU. Their primary functions are to secure oxygen permeability of the finished product and to make protect it from fouling. PFAS are only used as a raw material and as a part of a mixture intended for polymerisation. There are no other PFAS or PFAScontaining compounds used in any other production processes.
The PFAScontaining mixture is used to produce polymer rods, which are then cut into standardsized buttons. This is done outside the EU. The buttons are then imported within the EU, where they are cut into lenses, with material carved into a lens and then polished.
12 Gas permeable contact lenses are rigid lenses that allow oxygen to pass through the lens. They are also called GP lenses, rigid gas permeable lenses, RGP lenses and oxygen permeable lenses. RGP lenses are particular because they are made from a firm and durable plastic material, which allows them to retain their shape and ensure sharp vision.
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Figure 3: A comparison of material versus lens production
Figure 3 above shows that lens materials are manufactured outside the EU, and the lenses are produced in the EU.
When the button is lathed into a lens, it is a highprecision operation. On the average, the overall buttontolens ration is 5%. It is by necessity, because the lens is curved. The usual form of a button is a cylinder with diameter of 11.6 mm and a thickness of 4.5 mm. As a specific example, when a lens is 10 mm diameter with a thickness of 0.25 mm, the ratio is 4%.
Figure 4 below shows, in a simplified way, how the carving is done and why it is possible to make RGP lenses suited to individual needs of a patient. In computerdirect lathes, the plastic buttons are carved from which rigid gaspermeable lenses and some soft lenses are made. Technicians direct this carving using a topographic map of the patient's eye.
Figure 4: The carving of an RGP lens
3.1 Tisilfocon A13
Monomer
Material production - Outside EU
Polymerizatio n
Strain removal
Blank lathing
Release inspection
Lathing
Polishing
Lens production - Inside EU
Inspection
Surface processing
Storage, filling, packaging
Release inspection
The key material Menicon uses for manufacturing RGP lenses is Tisilfocon A. Tisilfocon A has a molecular formula of C57H83F6NO14Si4 and a molecular weight of 1232.6 g/mol. Figure 5 below illustrates the Tisilfocon A molecules.
13 https://pubchem.ncbi.nlm.nih.gov/compound/TisilfoconA 15
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Figure 5: Tisilfocon A
The component compounds of Tisilfocon A molecules are:
CID 16051823 (pVinylphenyltris(trimethylsiloxy)silane)
CID 7355 (Glycol Dimethacrylate)
CID 76469 (Hexafluoroisopropyl methacrylate)
CID 4093 (Methacrylic Acid)
CID 14794067 ((4Ethenylphenyl)methyl 2methylprop2enoate)
CID 6917 (NVinyl2pyrrolidone)
Tisilfocon A is compliant to all technical requirements to contact lenses and contact lens care products. Mandatory requirements to CLs are outlined in ISO 14534:2011 "Ophthalmic optics -- Contact lenses and contact lens care products -- Fundamental requirements".14 Accordingly, the performance of contact lenses shall be demonstrated by an evaluation of existing information and history of human use, together with, if necessary, preclinical and clinical testing.
In assessing safety and performance, each of the following shall be considered and the decisions shall be documented:
Functional characteristics, intended purpose, and conditions of use;
14 The following key international standards complement this one (a full list available in Annex I): ISO 11978, Ophthalmic optics -- Contact lenses and contact lens care products -- Information supplied by the manufacturer; ISO 11980, Ophthalmic optics -- Contact lenses and contact lens care products -- Guidance for clinical investigations; ISO 11987, Ophthalmic optics -- Contact lenses -- Determination of shelflife; ISO 13212, Ophthalmic optics -- Contact lens care products -- Guidelines for determination of shelflife; ISO 14155, Clinical investigation of medical devices for human subjects -- Good clinical practice; ISO 14971, Medical devices -- Application of risk management to medical devices; ISO 152231, Medical devices -- Symbols to be used with medical device labels, labelling and information to be supplied -- Part 1: General requirements; ISO 183691, Ophthalmic optics -- Contact lenses -- Part 1: Vocabulary, classification system and recommendations for labelling specifications; ISO 183692, Ophthalmic optics -- Contact lenses -- Part 2: Tolerances.
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Specific requirements for rigid contact lenses and hydrogel contact lenses as specified in ISO 183692 (the tolerance limits of the principal optical and physical parameters of rigid corneal, rigid scleral and soft contact lenses at the time of manufacture};
Microbiological properties, including bioburden, sterility, contact lens disinfection, and preservation activities;
Biocompatibility, including extractable substances, cytotoxicity, irritation, sensitization, sterilization residues, and degradation products -- the relevant requirements of ISO 109931 shall apply 15;
Clinical evaluation; Physical and chemical compatibility (including any preservative uptake and release) between
contact lenses and contact lens care products, and other accessories for contact lenses as specified in ISO 1198616; Stability, including shelflife and discard date; Other intended purposes, e.g., cleaning efficacy or measuring function.
To satisfy the conditions listed above, materials used for and during the manufacture of contact lenses shall be chosen with regard to the properties necessary to meet the requirements for safety, performance, manufacture, handling, and compatibility with other materials with which they may come into contact, and the reasons for choosing the selected materials shall be documented.
All contact lenses placed on the EU market are ISOcompliant. This means they are made from materials that had been evaluated to prove their safety, biocompatibility, lack of cytotoxicity, stability and performance.
To be usable, a contact lens should possess a combination of several physical properties. Figure 6 below shows the most important ones.17 It also shows that a specific lens is always a result of a trade off. For instance, a lens cannot be both rigid, and consequently suited to fitting an individual eye exactly so as to deliver an excellent visual acuity even for patients with complicated corneal issues, and to have a highwater content at the same time. Typically, the water content of an RGP lens is less than 1%.
15 ISO 109931, Biological evaluation of medical devices -- Part 1: Evaluation and testing within a risk management process. 16 ISO 11986, Ophthalmic optics -- Contact lenses and contact lens care products -- Determination of preservative uptake and release. 17 Musgrave, C. (2022). Contact Lens Materials - A Materials Science Perspective. Available at: https://encyclopedia.pub/entry/18834 (Accessed in July 2023).
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Figure 6: An overview of the most important physical properties of a contact lens
The two main categories of contact lenses are soft contact lenses, primarily represented by lenses made using (silicon) hydrogel material, and rigid contact lenses, now represented almost exclusively by RGP contact lenses.
As defined by the relevant ISO standard, soft contact lens is a contact lens, which is easily deformable and may not retain its form without support while rigid contact lens is a contact lens, which, in its final state and under normal conditions, retains its form without support and has a water content up to 10%.18 While soft lenses are made from hydrogel (usually) and nonhydrogel (rarely) materials, rigid contact lenses are made of nonhydrogel rigid materials, which can flex slightly but do not substantially conform to the shape of the cornea when on the eye.
By definition, rigid gaspermeable (RGP) contact lens is a contact lens manufactured from a rigid material containing one or more gaspermeable compounds in sufficient concentrations to facilitate transport of oxygen through the lens and having a Dk equal to or greater than 10 Dk units.19 And oxygen permeability (Dk) is oxygen flux (j), under specified conditions through contact lens material of unit thickness when subjected to unit pressure difference. This is the most commonly used gas
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permeability for contact lens materials.
Oxygen permeability is expressed in units of 10-11 (cm2/s) [ml O2/(ml mmHg)]. For simplicity, the units for Dk are referred to as Barrer or "Dk units". Oxygen permeability is a physical property of the material and is not a function of the shape or thickness of a contact lens or material sample.
18 ISO 183691:2017 19 Idem. 20 oxygen flux (j) is net volume of oxygen gas passing through a unit area of sample contact lens material per unit time under specified conditions, including temperature, sample thickness and partial pressures of oxygen on both sides of the sample.
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Oxygen Permeability
High oxygen permeability is one of the critical functions for the contact lenses intended for prolonged wear. The lack of oxygen permeability was a major problem with PMMA, which was the first material used in contact lenses. PMMA lens wear acidifies epithelial cells by preventing CO2 emissions and inducing hypoxia, leading to serious conditions like corneal edema. It was clinically proven that fluorinated components significantly reduce adverse reactions and wearinduced eyes infection during various studies conducted at the stage of transition from PMMA to oxygen permeable materials.
There is wide scientific evidence that increasing the oxygen permeability of lenses reduces the harm to the corneal epithelium and that the amount of oxygen deficiency in the cornea decreases with the increase in lens oxygen permeability. Both experimental and observational studies conducted since the end of 1980s confirmed the connection between gas permeability and corneal sensitivity.21 There are also some recent studies that demonstrate that the harm done to cornea by lowpermeability lenses might be partly reversible by fitting the patients with RGP lenses.
To summarize, gaspermeability is a fundamental characteristic, because the higher it is, the more patients are protected from eye infections and corneal degradation. From the technical point of view, there is an upper limit on the gas permeability achievable by soft contact lenses, above which only RGP lenses, made in a different way and from different polymers, can go. Therefore, RGP lenses are more suited for prolonged wear, and the socalled "night lenses" (worn overnight only), or orthokeratology lenses, which are meant to improve or contain myopia through corneal reshaping, cannot be made from soft lens materials.
Inert Surface
The process of accumulating deposits starts as soon as lenses come in contact with the eye and the environment. Protein and lipid deposits, in particular, are known to impact visual acuity, diminish wear comfort and lead to various ocular infections, including papillary conjunctivitis, punctate keratitis, corneal inflammatory events and even microbial keratitis. 22,23
Proteins are present in the tear film, and are useful components thereof. But when on a contact lens, proteins are prone to denaturation, losing their natural protective function and altering surface of a lens. This makes it easy for bacteria to attach to a lens surface and produce an eye infection. Lipids in this situation are predisposed to oxidation and degradation, which also distorts a lens surface, creating conditions for bacteria binding to it. To prevent this, the lens surface should be inert, meaning "not chemically reactive".
21 An overview of the key studies is represented in Annex II. 22 Cope, J.R., et al., 2017. Risk behaviors for contact lens-related eye infections among adults and adolescents-- United States, 2016. Morbidity and Mortality Weekly Report, 66(32), p.841. Doi: 10.15585/mmwr.mm6632a2 (Acessed in June 2023).
23 Aswad, M.I., et al., 1990. Bacterial adherence to extended wear soft contact lenses. Ophthalmology, 97(3), pp.296302. Doi: https://doi.org/10.1016/S01616420(90)325964 (Accexxed in June 2023).
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Fluorinated compounds are necessary to achieve inert surface. The surface energy of fluorinated compounds is very low and inert, which reduces adhesion to both proteins and lipids. The surface energy of silicones is also low, but lipophilic.24 First contact lenses, made from PMMA, were deposit resistant, but impermeable to oxygen. Then, silicone was added to the lens material to create silicone acrylate (SA) lens materials. This resulted in some increase in oxygen permeability. However, silicone monomers used at this stage could not provide high oxygen permeability, which is necessary especially for patients with irregular corneas or postoperative. The introduction of 3[tris (trimethylsilyloxy)silyl]propyl methacrylate(TRIS) was the turning point, but it also led to a decrease in hardness of a finished lens and to lipid deposits. The fluorinated compounds were introduced to solve those issues while keeping oxygen permeability high and, later, ultrahigh.
Lens deposits create many safety and usabilityrelated concerns for contact lens wearers. The presence of a fluorinated compound in RGP lenses addresses these concerns, because it has only negligible interactions with biological materials, including lipids and proteins, due to its chemical inertness. Thus, any potential alternative should also ensure comparable surface characteristics to grant patients a comparable level of safety.
Hardness
Hardness might seem not to be a sophisticated characteristic for a material per se, but when it is necessary to combine it with a high gaspermeability and an adequate wettability, this becomes a challenge. To be rigid, the lens material should have Shore D hardness of at least 70.
Figure 7 shows scales of Shore D hardness in comparison to domestic objects.25
Figure 7: Shore hardness scales
All modern RGP lenses applications are grounded in their rigidity. That property allows to achieve satisfactory acuity in patients with cornea conditions. It also allows to manufacture individually fitted lenses suited to needs of a specific patient. Soft contact lenses are not able to conserve their shape
24 A high surface energy means a strong molecular attraction, therefore easier to bond, whereas a low surface energy means a weak molecular attraction, therefore harder to bond. To prevent fouling, a surface should be both nonadhesive, or low energy, and inert, or not chemically reactive. 25 Smoothon, Durometer shore hardness scale. Available at: https://www.smoothon.com/page/durometer shorehardnessscale/ (Accessed in June 2023).
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because they are designed to adapt to an average patient's eye, and in patients with some eye conditions this suppleness is counterproductive.
Rigidity of RGP lenses causes a reshaping of the cornea, thus making them useful for postsurgery treatment. RGP contact lens are regarded as the most suitable nonoperative management option for patients with keratoconus, a chronic progressive disease characterized by thinning and expansion of the cornea, which protrudes forward in a conical shape.26,27 They are also the firstchoice treatment for correcting irregular astigmatism after corneal transplantation.28
Orthokeratology (orthok), the process of deliberately reshaping the anterior cornea by specialty contact lenses worn overnight, is being more and more used to slow the progression of myopia in children. This treatment utilizes reverse geometry lens designs, which can only be produced with highly oxygen permeable and rigid materials.29
Figure 8 on the next page contains a list of materials commonly used for manufacturing RGP contact lenses and specialty lenses. The materials listed are ranged according to their oxygen permeability (Dk). All these materials include fluorinated components.
26 Vincent, S.J., AlonsoCaneiro, D. and Collins, M.J., 2014. Corneal changes following shortterm miniscleral contact lens wear. Contact Lens and Anterior Eye, 37(6), pp.461468. Available at: https://doi.org/10.1016/j.clae.2014.08.002 (Accessed in June 2023). 27 Zhang, X.H. and Li, X., 2020. Effect of rigid gas permeable contact lens on keratoconus progression: a review. International Journal of Ophthalmology, 13(7), p.1124. Available at: https://doi.org/10.18240%2Fijo.2020.07.17 (Accessed in June 2023). 28 Gao, H., Chen, X.N. and Shi, W.Y., 2019. Analysis of the prevalence of blindness and major blinding diseases in China. [Zhonghua yan ke za Zhi] Chinese Journal of Ophthalmology, 55(8), pp.625628. Available at: http://dx.doi.org/10.18240/ijo.2020.07.17 (Accessed in June 2023). 29 Vincent, S.J., Cho, P., Chan, K.Y., Fadel, D., GhorbaniMojarrad, N., GonzlezMijome, J.M., Johnson, L., Kang, P., Michaud, L., Simard, P. and Jones, L., 2021. BCLA CLEAROrthokeratology. Contact Lens and Anterior Eye, 44(2), pp.240269. Available at: https://doi.org/10.1016/j.clae.2021.02.003 (Accessed in June 2023).
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Table 1: Key technical characteristics of RGP lens materials available on the market30
30 Available at: https://lensmaterial.info/gpmaterialsallproperties (Accessed in June 2023). 22
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3.2 RGP lens uses
All rigid gas permeable contact lenses currently manufactured contain PFAS, because only use of PFAS allows to combine properties necessary to satisfy therapeutic needs of wearers of RGP lenses. While is it possible, though complicated, to manufacture PFASfree soft lenses, RGP lenses should be highly oxygenpermeable, which is not achievable with siliconehydrogel solutions. Rigid lenses maintain their own shape, while soft contact lenses are easily deformable and require support for proper shape. As of 2017, 14% of all contact lenses wearers in the USA were fitted with RGP lenses.31
PMMA (not permeable) hard lenses are still manufactured, but in negligible quantities. As of 2017, PMMA CLs occupied a market share of about 1%.32 Their sole application is for treating patients with extreme tear film issues.
While soft contact lenses are superior to RGP lenses in terms of comfort, RGP lenses have higher oxygen permeability and tear exchange rate and therefore are safer. That's why RGP lenses are recommended by medical professionals to their patients.33 RGP lenses also outperform soft lenses as regards quality of vision (QOV), and there are contact lens wearers who prefer RGP lenses because of that. RGP contact lenses, as a rule, cost more per lens than soft lenses, bus as they are extremely durable, they are less expensive longterm.
Typically, RGP lenses are used by patients who are unable to achieve an acceptable level of visual acuity with glasses or soft contact lenses. They are:
Patients who need astigmatism correction; Patients with keratoconus and other irregular cornea issues; Postsurgery patients; Patients with presbyopia who need bifocal correction.
RGP lenses are also used in orthokeratology. Orthokeratology is a noninvasive and nonsurgical process, during which specially designed RGP lenses are fitted to a patient. This process temporarily reshapes the cornea to improve vision. Children and teenagers with myopia, which are usually not eligible for refractive surgery, can benefit from orthokeratology (myopia correction) and myopia management to inhibit the myopia progression in children.
3.2.1 Irregular astigmatism
Irregular astigmatism is an umbrella eye condition occurring when the curvature of the eye's surface is not only not rotational symmetric, as in regular astigmatism (rugby ball versus football shape), but when this surface is also uneven, or curved in multiple directions. In cases of irregular astigmatism glasses or soft contact lenses are typically unable to provide satisfactory visual correction due to
31 Musgrave, C. (2022). Contact Lens Materials - A Materials Science Perspective. Available at: https://encyclopedia.pub/entry/18834 (Accessed in July 2023). 32 Idem 33 Tear exchange is the fluid circulation between the pre and the postlens tear film. This exchange, which facilitates the fluid replenishment, is considerably lower during the wear of soft lenses compared with rigid lenses.
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irregularity of the corneal surface. Fitting patients with RGP lenses, including coneshaped cornea lenses and scleral lenses, is a way to provide better visual acuity and comfort, making them an effective option to improve the QOV (quality of vision) and QOL (quality of life) for patients. Figure 9 represents an advanced case of keratoconus.
Figure 8: An advanced case of keratoconus
The causes of irregular astigmatism include, for example: Keratoconus; Pellucid marginal degeneration; The effects of corneal transplantation; The effects of refractive corrective surgery; Severe dry eye.
Conventional RGP lenses are the firstchoice treatment for irregular astigmatism. If they fail, the next option is a scleral lens, which is larger than a conventional RGP lens and rests either between the cornea and the sclera or on the outer sclera. Scleral lenses, also called specialty lenses, proved successful when treating most patient with distorted corneas that are intolerant to other forms of vision correction.34
3.3 PFAScontaining products
The products produced from the fluorinated matrix are rigid gas permeable contact lenses marketed under the brands Menicon Z, Menicon EX, Menicon Tinu and ROSE K. Menicon has two RGP lenses producing plants in the EU, one in Emmen (the Netherlands) and one in France. RGP lenses produced in the EEA are sold in the EEA, the USA, China and Singapore.
Each lens manufactured by Menicon belongs to a lens design family. The main lens design families are Exact, Daytime, GeniuS, Flexi, Conform, RoseK, and Time. Each lens design family contains products for different applications and/or combinations, including Single Vision, Toric (Astigmatism), Presbyopia and medical applications.
34 An overview of scientific literature is represented in Annex B 24
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Product name: Single vision lenses:
Exact Daytime Genius Flexi BC Flexi TC Flexi FLTC (keratoconus) Menicon Z (lens design) Menicon Ex (lens design) Menicon Zalfa (lens design) Toric lenses: Daytime Toric Daytime CEbitoric Exact CEbitoric Exact Fronttoric Exact SEbitoric Genius CEbitoric Genius SEbitoric Genius Fronttoric FLTC CEbitoric FLTC SEbitoric FLTC Fronttoric FLTC SEbitoric Presbyopic lenses Daytime Oblong Daytime Oblong Forte Daytime Oblong Inverse Daytime Prepair Exact Longline Exact Oblong Exact Oblong Forte FLTC Longline Genius Longline Genius Oblong Genius Oblong Forte Genius Oblong Inverse Genius Prepair Presbyopic Toric lenses Daytime Toric Oblong Daytime Toric Prepair Daytime CEbitoric Oblong
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Daytime CEbitoric Prepair Exact CEbitoric Oblong Exact CEbitoric Oblong Forte Exact SEbitoric Oblong Exact SEbitoric Oblong Forte Genius CEbitoric Oblong Genius CEbitoric Oblong Forte Genius CEbitoric Prepair Genius SEbitoric Oblong Genius SEbitoric Oblong Forte Genius SEbitoric Prepair Conform Conform Conform 360 Conform Oblong Conform 360 Oblong Conform Oblong Forte Conform 360 Oblong Forte Menifocal Medical applications: Rose K Rose K2 Rose K PG Rose K IC Rose K NC Ortho K Nachtlens Nachtlens 2 Nachtlens 2 Toric Nachtlens PRO Toric Menicon Bloom Night Menicon Bloom Night Toric Scleral lenses Sclera B TimeXL TimeXL BT TimeXL Multifocal TimeXL BT Multifocal TimeXXL TimeXXL BT TimeXL passet
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Most of the lens designs listed above are offered in different lens materials provided by different suppliers. These materials have, for instance, different handling tints, for contrast between the lens and the surface. Materials used are Menicon Z, Menicon EX, Optimum Comfort/Extra/Extreme, Paragon HDS, and Boston ES.
3.3.1 Menicon Z lens material
Menicon Z (tisilfocon A) is applicable for spherical, aspheric, prism ballast toric and prism ballast multifocal lenses are indicated for daily wear for the correction of refractive error (myopia, hyperopia, presbyopia and/or astigmatism) in aphakic and nonaphakic persons with diseased and nondiseased eyes as is described in the above list of products.35
Especially the lenses with a medical application (Rose K and Scleral lenses) may be prescribed for daily wear in otherwise nondiseased eyes that require a rigid contact lens for the management of irregular corneal conditions such as keratoconus, pellucid marginal degeneration, or following penetrating keratoplasty or refractive (e.g., LASIK) surgery.
Lenses may be prescribed in spherical and aspheric powers ranging from 35.00 D to +35.00 D. Toric lenses are designed to correct up to 10.00 D of astigmatism and multifocal lenses to provide up to +5.00 D of reading add power. These are optical parameters. Besides, there is a range of specific parameters as regards fitting characteristics.
The Menicon Z lens material, tisilfocon A is a thermoset copolymer derived from fluoromethacrylate and siloxanylstyrene, bound by crosslinking agents. This chemical structure results in excellent mechanical properties, allowing the lens to be made significantly thinner than a typical rigid gas permeable lens. Historically, the strength of gas permeable materials would decrease as oxygen permeability increased. However, Menicon has worked to create a new material with both enhanced strength and hyper oxygen permeability, which allows for lenses to be made thinner and improves comfort.
The oxygen permeability (Dk 163 ISO /189 Fatt) of Menicon Z exceeds all other GP materials. Menicon Z is the first material to be classified in the "hyperoxygen transmissibility" category by a leading expert in the field of oxygen permeability research.36
Menicon Z impact on corneal endothelial morphology was tested in a comparative study by Barr et al., and the results were published in 2003.37 There were no significant endothelial cell morphology changes after 1 year of nearly continuous contact lens wear, even if the RGP wearers in the study were
35 Aphakia is the absence of the lens of the eye produced by surgery, accident or erforating wound or ulcer, or congenital anomaly. 36 Benjamin WJ. EOP and Dk/L: the quest for hyper transmissibility. J Am Optom Assoc. 1993 Mar;64(3):196 200. PMID: 8454837. 37 Barr JT, Pall B, Szczotka LB, Mitchell GL, Gleason W. Corneal endothelial morphology results in the Menicon Z 30day continuouswear contact lens clinical trial. Eye Contact Lens. 2003 Jan;29(1):146. doi: 10.1097/0014006820030100000004. PMID: 12769149. https://pubmed.ncbi.nlm.nih.gov/12769149/
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older by an average of 10 years (mean age approximately 40) and had worn their contact lenses an average of almost 10 years longer than the soft contact lens wearers.
The evaluation was conducted as part of a protocol entitled Evaluation of the Menicon Z Rigid Gas Permeable Contact Lens for up to 30 Days Extended Wear. The purpose of the protocol was to compare corneal endothelial morphology changes after wearing rigid gaspermeable (RGP) Menicon Z contact lenses, continuously for up to 30 days, with ACUVUE (Johnson & Johnson Vision Care) hydrogel contact lenses, worn for up to 6 nights of extended wear.
Sixty patients, who were adapted to RGP daily wear and soft contact lens daily wear, were recruited at two study sites. The thirty subjects who wore RGP daily wear lenses were fitted with the Menicon Z (tisilfocon A, oxygen permeablility [Dk] = 163) RGP contact lens comprised the test group. The control group subjects (n = 30 former users of daily wear soft contact lenses) were fitted with ACUVUE (etafilcon A, Dk = 28) hydrogel contact lenses. After a 2week adaptation period of daily wear, subjects began extended wear. The hydrogel lens group was instructed to wear their lenses for 7 days and 6 nights before discarding the lenses and to sleep with no lenses on the seventh night. The RGP group was permitted to wear the lenses for up to 30 days and 29 consecutive nights before removing the lenses for cleaning and overnight soaking.
Menicon Z has also proved its efficacy for patients with keratoconus. In 2008 SzczotkaFlynn et al.38 fitted Menicon Z lenses with a design for keratoconus in 33 eyes of 20 keratoconus patients and 31 eyes of 23 patients with irregular corneas (21 eyes postcorneal surgery, 1 eye with ocular cicatricial pemphigoid, and 2 eyes with chronic bacterial keratitis) with the treatment goals of safety (corneal physiology), comfort, and visual satisfaction. Except for six eyes, the patients had used lenses other than Menicon Z (other RGP, SCL, no correction, etc.) before the study. The success rate of the comprehensive evaluation of treatment goals was 82% (27/33 eyes) in the keratoconus group and 74% (23/31 eyes) in the irregular cornea group (surgical and ocular surface diseases), demonstrating high patient satisfaction. Among the six eyes that failed to succeed in the keratoconus group, four eyes had been previously fitted with other RGP materials, indicating that over 90% of the patients obtained therapeutic effects from RGP lenses.
When registering in the US, Menicon claimed substantial equivalence of the Menicon Z (tisilfocon A) to Rose K Post Graft Rigid Gas Permeable Contact Lenses, Boston XO (hexafocon A), Boston EQ (enflufocon B) and Boston ES (enflufocon A) Rigid Gas Permeable Contact Lenses.
3.3.2 Annual volume of PFAS used
The average annual volume of materials used to produce RGP lenses is 400 kg. The exact amount of PFAS processed in 2022 was 157.16 kg, including 5.1 kg used in lenses (Equivalence: 100.000 lenses per kg PFAS) and 152.06 kg of PFAS waste.
38 SzczotkaFlynn LB, Patel S. Menicon Z rigid gas permeable lenses for keratoconus and irregular corneas: a retrospective case series. Eye Contact Lens. 2008 Sep;34(5):25460. doi: 10.1097/ICL.0b013e31817f6db0. PMID: 18779664.
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3.3.3 RGP lens material: R&D process
Rigid lens materials have played an important role in the development of contact lens materials generally, because the first contact lenses on the market were rigid. The original rigid contact lens material was polymethyl methacrylate (Perspex). This material was nontoxic, biologically inert, hard and transparent. Importantly, it could be easily molded to fit individual needs of the patient. On the downside, its oxygen permeability was extremely low, and that's why it was phased out as soon as alternatives emerged.
The invention of highly oxygen permeable fluorosilicone acrylate materials was a major breakthrough. In particular, it made orthokeratology (night lenses) possible as these lenses facilitate acceptable levels of corneal oxygen permeability for healthy overnight wear.
Menicon's founder Kyoichi Tanaka set up the Japan Contact Lens Research Institute in 1952. Since then, Menicon has been conducting R&D activities in all areas related to contact lenses, including CL materials. The R&D activities related to RGP CL materials are conducted in Japan. The R&D Center for RGP optical design has been established in the Netherlands.
In Menicon's experience, development of a new mixture to be used for producing contact lens material, even in a case when only one substance is new, is estimated to take at least 24 years, including testing and validation stages. First of all, it is necessary to test all specific properties of a new material. After that, the manufacturing process needs validation on at least 3 material batches.
When a new material becomes available for contact lenses, the lens manufacturer needs to design a new lens based on the specific material characteristics. After design phase, manufacturing testing and validation is needed. Biological safety needs to be proven of the final product.
When biological safety is confirmed, efficacy needs to be proven by a clinical study, starting with an approval from the ethical committee, recruitment of patients, test phase and reporting. The time needed to conduct a clinical study can vary from 1 to 3 years (conservative estimate), depending on the claims and lifetime product. Shelf life (typical 1 to 2 years depending on application) also needs to be determined through realtime and accelerated testing.39 Only after going through all these steps to confirm safety and efficacy of a new lens, an application could be submitted for market approval to a notified body.
On the average, between 5 and 8 years are needed to get a new article on the market. The key stages are:
Lens design stage - 612 months; Manufacturing process validation - 612 months; Biosafety testing - 6 18 months;
39 Shelf life is commonly estimated by two different stability testing procedures: realtime tests and accelerated tests. Shelf life studies conducted at ambient temperature are considered realtime while accelerated testing is done at a higher temperature. In particular, according to the relevant ISO standard 11987 "Ophthalmic optics -- Contact lenses -- Determination of shelflife", accelerated shelflife testing conducted at 35C reduces time by factor of 2.
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Clinical study - 1236 months; Shelflife determination - 612 months; Market approval - 1236 months from the date of submission.
All the estimates above are made for a situation when a new material is available and its ISO compliance has been already confirmed. Reflecting on past RGP projects, Menicon needs 1013 years to place a new RGP product on a market if it includes developing a new material. However, all the RGP projects accomplished by Menicon up to now have been based on availability of fluorinated compounds.
Menicon has stateoftheart research facilities focused on three functions: 1) product development, including research on materials and designs; 2) clinical research for clinical evaluation of eye safety and product efficacy; and 3) research on technologies that enable efficient mass production of high quality products. The Company has patented groundbreaking inventions related to CLs, CL manufacturing methods, polymer materials and disinfection systems. Still, at the moment Menicon does not have in its pipeline any research projects involving fluorinefree RGPs. That is the reason why Menicon asked FINDEST, a company specialized on AIenabled technologies/innovations scouting, to conduct an artificial intelligence study, with the goal to identify potential alternatives.
3.3 AI (Artificial Intelligence) search
Human intelligence is always subjective, and biased by its very nature. Artificial intelligence works without prejudice, and it is only limited by explicitly set constraints, free to explore any avenues. The IGOR AI searchalgorithm, developed by FINDEST, reads and interprets technology descriptions in science using natural language processing (NLP). This enables IGOR AI to acquire functional technological knowledge directly from scientific articles and patents.
AI scouting procedure was designed so as not to overlook any potential substitute, be it substance, additive, component, technology or combination of the previously mentioned. At the initial stage, technical constraints imposed were minimal, to broaden the scope for potential alternatives as much as possible, and even at the final stage not all properties, which are necessary in a reallife lens, were imposed as constraints.
To identify possible alternatives, three rounds of AI search were performed, with the following requirements used:
Transparency > 88 % Mechanical properties (hardness Shore D >70, Youngs modulus > 1300MPa) Gas permeability Biocompatibility (safety for use in humans) Wettable surface Polymeric material
The AI search focused on the identification of PFAS alternatives in its application in rigid contact lenses. The goal was to identify alternative materials based on key material requirements of the PFAS compound.
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The first phase mapped materials which meet the first criteria needed for lenses, transparency, with light transmission >88% visible light. The second phase focused on agents that can increase the gas/oxygen permeability of lenses. This phase listed the substances that have been claimed to contribute to increase permeability in the context of lenses in general, not only rigid contact lenses. The search included both scientific and patent databases. The third phase focused on potential solutions which might combine high oxygen permeability and antifouling properties (hydrophobicity/wettability).
Phase I From the first AI search round (transparency), no leads have been identified as being substitutes to PFAS. This search yielded the following results, all of which were reviewed by Menicon's experts and found wanting:
Table 2: AI Search Phase 1
1. Polymers (general 2. Copolymers
1.1. Polymethyl methacrylate (PMMA) 1.2. Silicones 1.3. Polycarbonate (PC) 1.4. Polylactic acid (PLA) 1.5. Polyurethane (PU) 1.6. Polyethylene (PE) 1.7. Polyethylene terephthalate (PET) 1.8. Polyethylene naphthalate (PEN) 1.9. Polystyrene (PS) 1.10. Styrene Acrylonitrile (SAN) 1.11. Polymethylpentene (PMP, TPX) 1.12. Polyetherimide (PEI) 1.13. Polyamide (PA) 1.14. Polyphthalamide (PPA) 1.15. Polysulfones (PSU) 1.16. Polyvinyls 1.17. Polyesters general 1.18. Epoxies (thermoset) 1.19. Polyvinyl butyrate (PVB) 2.1. Thermoplastic polyurethane elastomers (TPUs) 2.2. Methyl methacrylateacrylonitrilebutadienestyrene (MABS) 2.3. Acrylonitrilestyreneacrylate (ASA) 2.4. Styrene methyl methacrylate (SMMA/MBS/MMBSMBS/MMBS) 2.5. Styrene Maleic Anhydride (SMA) 2.6. Ethylene Vinyl Acetate (EVA) 2.7. Cyclic olefin copolymer (COC) 2.8. Styrene Butadiene Block Copolymer (SBC) 2.9. Acrylonitrile butadiene styrene (ABS) 2.10. Polyolefin Plastomer (POP) 2.11. Ionomers
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3. Copolyesters
4. Fluor/ chlorinated polymers
3.1. Polyethylene terephthalate glycol (PETG) 3.2. Poly(cyclohexylene dimethylene cyclohexanedicarboxylate) (PCCE) 3.3. Poly(cyclohexane dimethylene terephthalate) (PCTG) 3.4. Poly(cyclohexane dimethyleneco2,2,4,4tetramethyl cyclobutylene terephthalate) (PCcBT) 3.5. Other copolyesters 4.1. Fluorinated Ethylene Propylene (FEP) 4.2. Ethylene tetrafluoroethylene (ETFE) 4.3. Perfluoroalkoxy alkane (PFA) 4.4. Chlorotrifluoroethylene (CTFE) 4.5. Polyvinyl chloride (PVC)
5. Biobased and bio polymers
6. Other
5.1. Cellulose acetate (CA) 5.2. Cellulose acetate butyrate 5.3. Other cellulosebased materials 5.4. Chitosan 5.5. Starchbased 6.1. Hydrogels (general)
The materials listed at this stage have been identified through 2 main search approaches: Due to their transparent nature: commercial suppliers claim transparencies above 88% Mention in connection to contact lenses: these leads have been identified in patents/science due to their use in contact lenses.
While the AI identified PMMA, a material which was actually widely used in contact lenses before the advent of RGP, and some materials currently used to manufacture soft contact lenses, no workable results were produced, and many proposed options were "fluorinated". At the second stage the approach was changed and became narrower, to exclude materials that are clearly unsuited to use in contact with a cornea.
Phase II The goal was to identify substances that act as agents to increase the oxygen permeability and either are used in contact lenses or are researched for use in a contact lens material. Technologies for improving oxygen permeability were also covered. This round brought many viable solutions, but all of them were related to manufacturing of soft siliconehydrogel or hydrogel contact lenses.
The list of substances and technologies proposed by the AI at this stage was as follows:
Table 3: AI Search Phase 2
1. Siliconbased substances
1.1. Siloxanes 1.2. Silanes 1.3. Silica sol 1.4. Silyl 1.5. Silicone compounds for contact lenses
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2. Inorganic (nano)particles
2.1. Silicone nanoparticles (SiNPs) 2.2. Cobalt oxide nanoparticles 2.3. Titanium nanoparticles 2.4. Chromium oxide nanoparticles 2.5. Gold nanoparticles 2.6. Perovskite oxides 2.7. Zirconium oxide and antimony tin oxide
3. Other substances
4. Fluorinerelated substances and methods 5. Other methods
3.1. Gelatin 3.2. Glycerol 3.3. Glycols as crosslinkers 3.4. NVinylpyrrolidone (NVP) and Polyvinylpyrrolidone (PVP) 3.5. Plasticizers (general) 3.6. Derivatives from itaconic acid 3.7. Polymerization with organosulfone monomer 3.8. Polymerizable hydrophobic monomer (unspecified) 3.9. Urethane 3.10. Hydroxyethyl methacrylate (HEMA) 3.11. Divinylbenzene as crosslinker 3.12. Vinyl bondcontaining monomer 3.13. Chitosan 4.1. Lenses containing fluorinated substances 4.2. Purging with fluorinecontaining gas 5.1. Porosity/freevolume and its impact on gas permeability 5.2. Curing process of lens to increase oxygen permeability 5.3. Local thickness changes to increase gas transmission in lenses 5.4. Water content and gas permeability of contact lenses 5.5. Lenses containing microchannels 5.6. Ion implantation to improve permeability 5.7. Supercritical fluid treatment 5.8. Electron Beam fabrication method
Silicones and siliconebased substances were featuring prominently at this stage, because they are used in soft contact lenses.
Phase III From the gas permeability agents mapping, a deep dive was performed. In this deep dive, further information and properties were extracted as to provide a means of direct comparison with PFAS. The result was a list including chemical agents, but not technologies, because all technologies identified earlier either assumed the use of fluorinated components or were suitable exclusively for manufacturing hydrogel CLs.
As a result, the following long list of potential alternatives was provided:
Table 4: AI Search Phase 3
Alternative
Used to enhance Used in RGP Hydrophobic? gas permeability contact lenses?
Shore Hardness D
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1. Fluorinated substances (benchmark) 2. Siliconebased substances
3. Silicone nanoparticles
(SiNPs)
4. Chromium
oxide
nanoparticles
5. Titanium nanoparticles
6. Cobalt
oxide
nanoparticles
7. Zirconium oxide and
antimony tin oxide
8. Perovskite oxides
9. Gold nanoparticles
10. Gelatin
11. Glycerol
12. Glycols as crosslinkers
13. NVinylpyrrolidone
(NVP)
and
Polyvinylpyrrolidone (PVP)
14. Derivatives
from
itaconic acid
15. Polymerization with
organosulfone monomer
16. Divinylbenzene as
crosslinker
17. Urethane
18. Hydroxyethyl methacrylate (HEMA) 19. Chitosan
agent in lenses? +
+
+
+
+ +
+
41
+
As an additive as well as main hydrogel component (gelatine hydrogel) +
As a crosslinker
+
+
+
As a crosslinker
+ Substituted into silicone To a degree
+
+
In combination with fluorinated substances
in hydrogels + in hydrogels in hydrogels in hydrogels In soft lenses Gelatine hydrogels
in hydrogels in hydrogels In siliconebased lenses In hard and semi hard lenses N/a
In hydrogels
+
+
+ +
amphiphilic40 n/a +
N/a
above 75 + +
n/a n/a n/a n/a n/a n/a n/a
n/a n/a n/a
+ + n/a +
+ n/a
40 The ratio of silicone to silica in silicon NPs studied for the use in CLs was 57.4% to 42,6%. Silicone is
hydrophobic, and silica is hydrophilic, and that results in the nanoparticles being amphiphilic. 41 The perovskite oxides studied for the use in CLs are based on silicone. The hydrogel containing 64.3 wt% of SiNPs demonstrated the oxygen permeability of about 76 barrer.
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Based on the information presented above, a maturity radar was generated to represent the key findings of the AI search in a simplified way. Information on application in contact lenses and number of documents (especially patents) found on the topic were also taken into account when visualizing the data. Please find below in Figure 9 the maturity radar.
Figure 9: Maturity radar
The main objective of the radar presented in this project is to visually display the relative match of the substances found when compared to the project topic of substitution of PFAS in RGP contact lenses. Substances found to be used in RGP as well as have a positive impact of gas permeability and antifouling properties are rated higher (close to the centre of the radar) than substances which do not meet these criteria. Substances which are used for gas permeability enhancement but are only used in hydrogel lenses are rated low and can be found on the outskirts of the radar.
The central white circle on the radar symbolizes market access. External layer of the scheme represents theoretical stage; the darker the color, the closer to "reallife" application. For an alternative to be considered mature (commercial stage), it should be located in the internal blue circle, next to the benchmark (1.1. Fluorinated substances). For instance, as regards siliconebased substances, their place on the radar suggests that they are both available and commercially used in a relevant area, but not as a substitute, because otherwise they would be adjacent to the central white circle.
This visualization demonstrates that while a comprehensive AI search failed to provide any promising notfluorinated alternatives, it was still possible to shortlist some tentative options for further analysis and discard those that are purely theoretical.
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3.4 Assessment of shortlisted alternatives
From the list provided by the deep dive (Stage 3 of AI search) most options already used (in combination with PFAS) were excluded, as well as completely immature alternatives (most nanoparticles) and the items lacking key properties (unable to prevent surface deposits).
Number Alternative name
Table 4: Shortlisted alternatives
CAS or EC Number (where applicable)
Material available?
1
Siliconebased substances
2
Silicone nanoparticles
3
Titanium nanoparticles
4
Chitosan
7440213
Yes
(Silicone)
7631869
Yes
13463677 Yes
9012764
Yes
Material
cleared for
use
in
medical
devices?
Yes
Yes Yes Yes
3.4.1 Alternative 1: Silicone based substances Siliconebased substances are polymers made up of siloxane (-R2Si-O-SiR2-, where R = organic group). Siloxane is a functional group in organosilicon chemistry with the Si-O-Si linkage. The parent siloxanes include the oligomeric and polymeric hydrides with the formulae H(OSiH2)nOH and (OSiH2)n. Siloxanes are manmade and have many commercial and industrial applications, including healthcare sector due to their biocompatibility, low thermal conductivity, and high flexibility. There are many applications of these polymers in antifog coatings due to their hydrophobicity. It means that water on the siicon coated surface becomes droplets and fall down, e.g., from a car window.
They are easily available on the market and are costeffective. They are also widely used as a component of lens materials, siliconebased hydrogels being the most common type of CL material today.
Technical feasibility Siloxane monomers are already used in RGP lens materials in combination with fluorinated monomers. Substitution of fluorinated components by silicone based ones would make the lens nonrigid, basically resulting in a different article, namely a soft contact lens. Soft lenses, while dominating the CL market, are not suited to the needs of patients with eye conditions demanding reshaping of cornea, and cannot be regarded as a substitute. Another issue with siloxane monomers is they don't prevent lipid deposition, which is critical for prolonged wear lenses.
Economic feasibility and economic impact Not evaluated seeing as technical feasibility is not achieved.
Availability Available.
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Hazard and risk Not applicable.
Conclusion Siliconebased substances cannot be seen as an alternative because they are unable to ensure the combination of properties necessary for patients with corneal issues or postsurgery.
3.4.2 Alternative 2: Silicone nanoparticles
Silicon nanoparticles (SiNPs) are biologically compatible, metalfree quantum dots that exhibit size and surface tailorable photoluminescence. In a 2020 study, silicone nanoparticles (SiNPs) were prepared from polydimethylsiloxane (PDMS) and tetraethyl orthosilicate (TEOS) via the solgel process.42 The resultant SiNPs were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and scanning electron microscope (SEM). These SiNPs were then blended with 2hydroxyethylmethacrylate (HEMA) and 1 vinyl2pyrrolidinone (NVP) before polymerizing into hydrogel contact lenses. All hydrogels were subject to characterization, including equilibrium water content (EWC), contact angle, and oxygen permeability (Dk). The average diameter of SiNPs was 330 nm. The results indicated that, with the increase of SiNPs content, the oxygen permeability increased, while the EWC was affected insignificantly. The maximum oxygen permeability attained was 71 barrer for HEMANVP lens containing 1.2 wt% of SiNPs with an EWC of 73%. These results demonstrate that by loading a small amount of SiNPs, the Dk of conventional hydrogel lenses can be improved greatly. It is possible that similar results could be achieved in the future with rigid lenses.
Technical feasibility SinNPs increase oxygen permeability. They are amphiphilic, with the ratio of silicone (hydrophobic) to silica (hydrophilic) as 57.4% to 42.6%. The resulting transparent material has a water content of a. 70%, which makes it not suited to RGP lens applications. Silicone nanoparticles segregate when added to the monomer mixture intended for RGP, making it inhomogeneous and therefore unusable. There is currently no technology allowing to prevent segregation of SinNPs,
Economic feasibility and economic impact Not evaluated seeing as technical feasibility is not achieved.
Availability Available (smallscale production).
Hazard and risk Not applicable.
42 Tran, N.P.D.; Yang, M.C. The Ophthalmic Performance of Hydrogel Contact Lenses Loaded with Silicone Nanoparticles. Polymers 2020, 12, 1128. https://doi.org/10.3390/polym12051128
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Conclusion Silicone nanoparticles need a technology breakthrough for being used in manufacturing of rigid lenses. As of now, the segregation issue precludes their use for potential substitution of fluorinated components.
3.4.3 Alternative 3: Titanium nanoparticles There is a recent study proposing a solution for high oxygen permeable ophthalmic lens materials involving SiNPs. Lee et al. used 2(Trimethylsiloxy)ethyl methacrylate (2T), 3 [Tris(trimethylsiloxy)silyl]propyl methacrylate (3T), [(1,1Dimethyl2propynyl)oxy]trimethylsilane (TMS), Poly(ethylene glycol) methyl ether methacrylate (PEGMA), Nvinyl2pyrrolidone (NVP) and titanium carbide nanoparticles as additives for the basic combination of synthesized silicone monomer (SiD) and N,NDimethylacetamide (DMA).43 And also, the materials were copolymerized with ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, azobisisobutyronitrile (AIBN) as the initiator. The copolymerization with a small amount of silane of about 1% increased the oxygen permeability to 30.3~33.52(cm2/sec)(mlO2/mlmm Hg)10-11, and in particular, the addition of titanium carbide nanoparticles was found to increase to 46.38 (cm2/sec)(ml O2/mlmm Hg)10-11. Surface modification was possible with various wetting agents. Especially, simultaneous use with titanium carbide nanoparticles increased the wettability while maintaining water content.
Technical feasibility It is impossible to add titanium nanoparticles to a monomer mixture so as to achieve a homogeneous material. No technology allowing to prevent segregation was identified during the AI search.
Economic feasibility and economic impact Not evaluated seeing as technical feasibility is not achieved.
Availability Available (medium to largescale production).
Hazard and risk Not applicable.
Conclusion Titanium nanoparticles might have been a great substitute, if there were a solution for the problems with segregation.
3.4. Alternative 4: Chitosan
43 Lee, MinJae; Sung, AYoung. Copolymerization of Acrylic Monomers and Silane Group Containing Titanium Carbide Nanoparticles for Application to Ophthalmic Lens Materials. Journal of Nanoscience and Nanotechnology, Volume 21, Number 8, August 2021, pp. 43884393(6). doi: https://doi.org/10.1166/jnn.2021.19432
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Chitosan is a naturally derived polymer (from chitin) with high bioavailability originating from the hydroxyl and amine groups within the structure, lending itself to lens modification. There have been recent experiments to improve the surface wettability of silicone hydrogel films by selfassembled hydroxypropyltrimethyl ammonium chloride chitosan mixed colloids. Chitosan does not improve oxygen permeability or mechanical properties. Menicon in 2014 has patented an RGP contact lens having a coating comprising a hydrogel, wherein the hydrogel is a quaternized chitosan hydrogel produced by a method comprising a step of polymerizing a polymerizable composition comprising a quaternized chitosan derivative having the following formula, wherein R and R are independently selected from the group consisting of optionally substituted C1 C18 alkyl, m is 2 or 3, n is 1 to 20.
Technical feasibility Chitosan is being researched as a potential therapeutic or antifouling coating (film) for ophthalmic and contact lenses, including RGP lenses. No commercial products using chitosan are available. It is insoluble in the monomer mixtures, so it is not possible to embed it into a monomer mixture intended for manufacturing of contact lenses.
Economic feasibility and economic impact Not evaluated seeing as technical feasibility is not achieved.
Availability Available (medium to large scale).
Hazard and risk Not applicable.
Conclusion Chitosan's use in contact lenses is at an experimental stage. All studies identified through AI search regard its potential applications in lens coatings, in particular for delivery of a medicinal product. The researchers have been using it to modify the surface of a lens, not in a potential lens material. The major concern, however, is that chitosan is of animal origin and consequently could provoke allergy reactions.
3.4.5 Conclusion on shortlisted alternatives
Any viable substitute for fluorinated compound should be able to produce the same key lens properties that are now provided by these compounds. The key contributions of fluorine compounds to RGP lens materials are oxygen permeability, mechanical properties (Share D, Young's Modulus) and antifouling properties. These contributions are derived from the unique properties of fluorine, which is the most electronegative of all the elements.
Siliconebase materials can achieve high oxygen permeability. The problem with all siliconebased lens materials, however, is that they are extremely prone to lipophilic deposits, which causes clinical issues. It is a critical disadvantage of these materials, and the fluorine compounds are the sole available solution to overcome it. This deposit issue cannot be avoided as long as silicone is used in RGP lens
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materials. It means that the future fluorinefree RGP material should be developed without silicone or almost without silicone while maintaining high oxygen permeability.
The analysis of alternatives concludes that no viable substitute is available now or will be available in the foreseeable future. An AI search specially designed to explore all available scientific literature and patents for a possible substitution did not reveal newly appeared options which would be worth investigating at the current stage. But even if there had been a potential replacement for fluorinated compounds, at the very least 2 years would be necessary to make it into a mixture suitable for lens production and another 5 years or more would be required to develop, assess and certify a new RGP lens. As a consequence, in the most likely "nonuse" scenario, Menicon will have no other option but to halt the production and sales of RGP lenses and correspondent LCPs in the European Union.
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4. Economic and Social Impacts
4.1 Economic impacts
The sections below provide a general overview of the economic impacts, including the business impacts on manufacturers of RGP contact lenses (i.e., EBIT loss and substitution costs) and the market impacts (i.e., on the product market). The economic impacts presented below consider Menicon's activities in the Netherlands, France, Germany, Italy, and Spain.
The market share covered by this impact assessment is approximately 40% of the EEA RGP contact lens market. As noted above, the market share of 40% is a highlevel estimation based on approximations made by industry professionals; there is no data available about the size of the niche RGP contact lens market. Based on this, we conservatively decide to not use this percentage to extrapolate the economic and social impacts to the EEA market.
4.1.1 Quantity of PFAS used in rigid gas permeable contact lenses and waste management Menicon has declared that potentially restricted PFAS ingredients are important for their business. 400,000 to 600,000 buttons (raw materials) are used by Menicon in the EEA to manufacture RGP contact lenses. Menicon uses PFAS for a total of 5.1 kg/year in RGP contact lenses (consumer products) in the EEA. 100,000 RGP lenses can be made per kg of PFAS. This means that around 500,000 RGP lenses are made yearly for an estimated number of 250,000 patients.
PFAS waste management
The total volume of waste is 394.74 kg per year. This contains 152.06 kg of PFAS waste. The waste is a polymer waste and contains 46 m/m % Hexafluorisopropyl methacrylate (a PFAS compound), among others. This waste is unsuitable for incineration in regular ovens. The waste is considered hazardous under category V4231 (Eural code 160305*), organic solids. It is therefore packed in UNapproved packaging (UNapproved plastic lidded drums), which is undamaged, closed in the correct manner, and clean on the outside. The waste is accordingly incinerated along with the packaging at an appropriate treatment facility.
4.1.2 Business impacts on manufacturers of rigid gas permeable contact lenses Over 100 to 200 product lines manufactured and placed on the Market by Menicon would be affected in case of a PFAS restriction. These product lines encompass different types of RGP contact lenses and RGP LCPs. LCPs are essential and indispensable products for the successful use of RGP lenses. Therefore, in the event that RGPs would not be able to stay on the market due to the PFAS restriction, LCPs specifically designed for RGPs would face a significant risk of disappearance as well. Section 2.4 provides an overview of different RGP contact lenses and LCPs. In the most likely "nonuse" scenario, Menicon will have no other option but to halt the production and imports of RGP lenses in the EEA.
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In 2022, Menicon's turnover from the total sales of RGP contact lenses was 25 to 30 M EUR in 2022 and the turnover from the total sales of RGP LCPs was 15 to 25 M EUR in the same year. This amounts to a total turnover from the total sales of 40 to 55 M EUR for these products in 2022.
If PFAS used in RGP contact lenses would be restricted, it is estimated that Menicon, a manufacturer of PFASbased RGP contact lenses, would face a net EBIT loss of approximately 7 to 10 M EUR/year.44 Over four years, the total impact is expected to be approximately 30 to 40 M EUR (NPV, 3% d.r.) for Menicon. 45 This includes the operating loss discounted over four years and oneoff costs as a consequence of the PFAS restriction (including oneoff compensation costs for personnel reduction and impairment development costs).
The main challenge that has been raised by Menicon is the fact that deadlines provided by authorities are considered too tight for business adaptability and for obtaining marketing authorisation for alternative products. The significant investments required to find alternatives provide an additional hurdle.
Substitution costs for Menicon
As stated by Menicon, it is difficult to estimate the costs associated with the substitution of PFAS in RGP contact lenses if alternatives were to become available. However, we can use the costs associated with the development of a past RGP contact lens product to calculate the approximated substitution costs to develop a new RGP contact lens product. The timeframe for the development of this past RGP contact lens product was 13 years, which is lower than the estimated timeframe to develop a PFAS free product. In addition, the costs to substitute PFAS are expected to be higher due to the importance of these substances in the technical performance of RGP contact lenses. The calculated substitution costs below should therefore be considered as a lower bound.
The costs associated with the development of a new RGP contact lens product include:
5 to 15 M EUR oneoff costs, including costs related to R&D and human resources.46 1 to 1.5 M EUR recurring costs (total over 9 years), including expenses on depreciable assets
(e.g., experiment equipment, etc.).47 150,000 to 250,000 EUR intellectual property (IP) recurring registration fees (total over 9
years).48 These fees are necessary to launch a new product.
44 Menicon was asked to consider how the revenues (and EBIT) for the year 2027 would be impacted under the assumption that a REACH restriction on PFAS used in the production of rigid contact lenses is to be fully adopted in the near future. 45 Using the Excel function =PV(3%,4,[CONF.],0,0)+ABS([CONF.])+ABS([CONF.]). 46 Using the average ECB exchange rate between 3 January 2022 to 30 December 2022 (1 EUR = 138.03 JPY) based on [CONF.] JPY. 47 Using the average ECB exchange rate between 3 January 2022 to 30 December 2022 (1 EUR = 138.03 JPY) based on [CONF.] JPY and using the Excel function =PV(3%, 9, ([CONF.]/9), 0, 0). 48 Using the average ECB exchange rate between 3 January 2022 to 30 December 2022 (1 EUR = 138.03 JPY) based on [CONF.] JPY and using the Excel function =PV(3%, 9, ([CONF.]/9), 0, 0).
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25,000 to 35,000 EUR registration authorities (RAs) fees.49 These fees are necessary to launch a new product.
The total expected cost for Menicon to produce a new RGP contact lens product can accordingly be conservatively estimated to be 5 to 15 M EUR. In reality, the substitution costs are likely to be much larger than this estimate.
4.1.3 Market impacts The proposed restriction on PFAS substances in articles would effectively prohibit manufacturing or importing RGP contact lenses in the EEA until alternatives are found. This is because the PFAS used are integral components for the lens blanks that are used to manufacture RGP contact lenses. A low number of suppliers could indeed lead to higher prices and supply chain dependences (monopoly or oligopoly). Shortage is also likely in case of the restriction. In sum, the market for RGP contact lenses will become minimal and have no prospects for the future as a consequence of a PFAS ban.
Impacts on distributors and downstream customers
A potential PFAS restriction would affect the distribution of Menicon's good and would therefore also affect Menicon's distributors and downstream customers, which are located in other EEA countries. Menicon's entities in the EEA have 20,000 to 25,000 distributors and downstream customers that purchase RGP lenses (that contain PFAS) or LCPs for RGP contact lenses. These downstream users include online retailers and optical stores, as well as eye care practitioners, opticians, and optometrists. Menicon's entity in France has the largest share of downstream customers that purchase RGP contact lenses (that contain PFAS) or LCPs for RGP contact lenses in Europe (50 to 60%), followed by Menicon's entity in Germany (15 to 25%).
Impact on R&D
There will likely be a negative impact on investments in R&D in general in the EEA in case of a restriction. Menicon's EEA R&D activities for RGP optical design are located in the Netherlands. Menicon has reported that a restriction will adversely affect their liquidity, operating profit, and overall turnover which, in turn, would negatively affect the resources available for R&D.
Impact on competition
Menicon has stated that competitors with a predominant focus on MTO (madetoorder) and disposable soft lenses, that also have business in the EEA, will benefit from an increase in demand for their contact lenses. The increased demand for MTO and disposable soft lenses, as a consequence of the PFAS restriction, will therefore adversely affect the competitiveness of companies that have a predominant focus on the RGP contact lens and RGP LCPs market. This would affect competition in the EEA contact lens market.
49 Using the average ECB exchange rate between 3 January 2022 to 30 December 2022 (1 EUR = 138.03 JPY) based on [CONF.] JPY.
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4.2 Social impacts
The sections below provide a general overview of the social impacts, including the impacts on unemployment and on contact lens wearers. The social impacts presented below consider Menicon's activities in the Netherlands, France, Germany, Italy, and Spain.
4.2.1 Impacts on unemployment
In general, it is difficult to estimate unemployment because this depends on whether the enduser market will completely accept different PFASfree RGP contact lenses. Moreover, the scale of the impact on employment is expected to be lower than the impact on EBIT.
Menicon employs 501 employees within the EEA, 75 to 100 of which are directly related to RGP contact lenses and RGP LCPs. The employees that are directly related to RGP contact lenses and RGP LCPs are either engaged in the production of these products or are supporting staff. It is estimated that, assuming a REACH restriction is implemented, 75 to 100 employees will face layoff in the EEA (in Menicon's entities in France, Germany, Spain, and Italy). Here we report the monetisation of the likely social costs of unemployment for these workers. The estimated average annual salary across these European employees that are directly related to RGP contact lenses and RGP LCPs (including the employer's social security contributions) is around 70,000 EUR.
A wellknown guideline in monetising the social impact of unemployment has been developed by the European Chemicals Agency (ECHA) for evaluating such an impact in different regulatory processes. Estimates have been made in accordance with the ECHA document on the evaluation of unemployment (SEAC/32/2016/04) 50 and the paper of Dubourg (2016) 51 endorsed by ECHA. Therefore:
Using Table A7 (column G, considering the gross wages including the employer's social security contributions) in Dubourg's paper, the total social cost of unemployment in EU is equal to 2.16 times the annual gross salary.52
Table 1 below presents the statistics from Eurostat (data for 2022Q4) on the average duration of unemployment for both men and women in the age class of 1564 years in EU27.53
Only 75% of the average duration of employment is considered, to reflect the fact that some affected workers are highly skilled and could find employment sooner.
50 ECHA, 2016. The Social Cost of Unemployment. Available at: https://echa.europa.eu/documents/10162/13555/seac_unemployment_evaluation_en.pdf/af3a487e65e5 49bb84a32c1bcbc35d25 51 Richard Dubourg, 2016. Valuing the Social Costs of Job Losses in Applications for Authorization. The Economics Interface Limited.
52 This value is greater than 1 because it takes into account the following components: lost wage, costs of job searching, recruitment costs, the impact of unemployment status on future wages (scarring effect) and employment possibilities, and leisure time (which is a benefit and therefore subtracted from the previous components).
53 Data extracted from: https://ec.europa.eu/eurostat/databrowser/view/LFSQ_UGAD custom_6675031/default/table?lang=en
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Table 5: Duration of unemployment in EU27
Duration Grouping
Less than 1 month From 1 to 2 months From 3 to 5 months From 6 to 11 months From 12 to 17 months From 18 to 23 months From 24 to 47 months 48 months or over
Total
Thousand units 1717.6 2658.0 2013.9 1779.0 1352.4 602.5 1459.7 1333.6
12916.7
Proportion (A)
0.132975141 0.205780114 0.155914436 0.137728677 0.104701665 0.046645041 0.113008741 0.103246185
1
Assumed duration (B)
0.5 1.5 4.5 8.5 14.5 20.5 35.5 48
Weighted average (A*B)
0.066487570 0.308670171 0.701614964 1.170693753 1.518174147 0.956223339 4.011810292 4.955816888 13.689491124
The estimate social costs of unemployment would therefore be equal to:
5 to 6 M EUR (including the employer's social security contributions) x 2.16 x 13.689491124/12 x 75% = 10 M EUR.54
Although the company would face a reduction in sales over the years, we assume for simplicity that the entire workforce will continue working for another three years. We therefore discount the monetised impact derived above by three years due to the assumed delay in the layoffs, using a discount rate of 3% per year, as follows: 10 M EUR x (1 + 0.03)3 = 9 M EUR.55
One can affirm with a high likelihood that the social impact of a restriction of PFAS used in the production of RGP contact lenses along the whole supply chain would be larger than 9 M EUR, once one considers all other economic operators that have businesses linked to Menicon, such as online retailers and optical stores, as well as eye care practitioners, opticians, and optometrists.
The following elements should be noted: All occupation groups are expected to be affected. As such, job losses are expected across the whole EEA. Overall, the company reported that their profitability would be affected. This would also have a negative impact on the wages paid to its workers (more likely in a worstcase scenario), as well as on working conditions and satisfaction.
4.2.2 Impacts on RGP contact lens users
The qualityoflife reductions for RGP contact lens users would be large in case of a potential PFAS restriction. RGP contact lenses, including corneal, (mini and full) scleral, daytime, hybrid, and
54 This is a rounded estimate. 55 This is a rounded estimate.
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orthokeratology contact lenses, are crucial for essential health purposes.56 Despite the dominance of soft lenses in the market, RGP contact lenses are either the only viable option or offer superior visual outcomes for individuals with specific eye and medical conditions.57 In addition, a large group of current RGP contact lens wearers cannot switch to alternatives such as soft lenses because they do not sufficiently correct visual acuity. The `analysis of alternatives' (section 3) provides more details on RGP lenses uses, as well as on the umbrella eye condition of irregular astigmatism.
To address optical lens powers and ultimately the impacts on contact lens users, a Diopter (Dpt) is the official unit of measurement, in which a negative value represents the more common case of myopia (75%) and a positive value represents hyperopia (25%).
Some key fundamentals for RGP contact lens users following the restriction of PFAS include: A spherical power vision loss of 40% per 1 Diopter. This means that if there is one Diopter lacking in the individual's optical system, the individual will experience a vision loss of 40%; Astigmatism vision loss of 80% per 1 Diopter. Compared to spherical powers, with astigmatism power, the vision is distorted further. In general, when an eye requires -0.75 Dpt of astigmatic power, lenses are required for optimal vision. This can be reached more easily with RGP lenses compared to soft lenses; Combinations of the above points will create an even greater loss in quality of vision; Mild and severe cornea irregularities have impact on the quality of vision and are compensated by the tear lens behind a RGP lens.58 This tear lens is absent in soft lenses as the soft lens adapts to the shape of the cornea; Quality of vision and quality of life will be substantially reduced due to a lack of oxygen permeability. In RGP lenses, the amount of oxygen permeability is higher compared to soft lenses, impacting the physiology of the eye. Patients with eye health problems need high oxygen permeable lenses, such as RGP lenses, to prevent them from removing and cleaning their lenses 10 to 15 times a day.
Currently, the application of RGP lenses ranges from -35 to +35 Dpt, with steps of 0.25 Dpt in between. Given that the most substantial amount, 60%, of RGP contact lens users have a Dpt of -10 to +10 Dpt, the aforementioned statistics will have severe impact on RGP contact lens users, in terms of vision loss, efficiency of use, and quality of life.
RGP contact lenses are either the only viable option or offer superior visual outcomes for individuals with high degrees of short or longsightedness, high astigmatism, corneal injuries, corneal conditions (e.g., keratoconus and keratoglobus), or for individuals who have undergone corneal grafts or refractive surgery.59 RGP contact lenses also address myopia, hyperopia, and presbyopia. RGP contact lenses used in orthokeratology also have a pivotal role in addressing the escalating global
56 Dossier Report prepared on behalf of Euromcontact. Eddleston M. D. 2023. The Essentiality of PFAS for Rigid Contact Lenses. 57 Dossier Report prepared on behalf of Euromcontact. Hepsen I. and Koppen C. 2022. The unique features and benefits of RGP contact lenses. European Contact Lens Society of Ophthalmologists (ECLSO). 58 The so called "tear lens" is the thin layer of tears formed beneath the RGP lens. 59 Ibid.
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issue of childhood myopia, which poses a heightened risk of severe visionthreatening complications such as macular degeneration, glaucoma, cataracts, and retinal detachment later in life.60
As highlighted in the `overview of rigid gas permeable contact lenses and lens care products' (section 2.4), all RGP contact lens design families and accompanying LCPs would be affected in case of a restriction. As noted above, a lens design family consists of multiple lens modalities for specific eye conditions and medical conditions or combinations. The qualityoflife reductions for RGP contact lens users would therefore be large in case of a potential PFAS restriction.
60 Eddleston M. D., Raduly L., Tapper T. T., Hughes R. J., Browne G. M. and Conway M. J. 2023. The Consequences of Removing Fluorinated Compounds from Rigid Gas Permeable Contact Lenses. Journal of Polymer Engineering. Available at: https://www.degruyter.com/document/doi/10.1515/polyeng2022 0189/html?lang=de
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5. Conclusion
This impact assessment and analysis of alternatives identify the main potential negative consequences that the EEA society at large would face in the framework of the potential REACH restriction of PFAS used in the production of RGP contact lenses. The assessment of the economic and social impacts has been performed in line with existing ECHA guidelines under REACH. The results are based on data provided by Menicon, a large manufacturer of RGP contact lenses, with a market share coverage of approximately 40% of the RGP contact lens sector.
Based on the evidencebased considerations above, the impact assessment and analysis of alternatives performed conclude that a broad restriction for the use of PFAS in rigid gas permeable (RGP) contact lenses will have disproportionate negative impacts on the European economy and society, as well as on the qualityoflife of RGP contact lens users. The analysis presented in this report reasonably justifies the request for a timeunlimited derogation for the use of critical PFAS in RGP contact lenses.
The above statement is founded on the following:
Menicon is positioned as an industry leader and pioneer in contact lens production. The company's main business areas are contact lenses, LCPs, medical instruments and supplies, and intraocular lenses. Menicon is the only manufacturer in the world that is dedicated to all areas of the contact lens industry, encompassing research and development, material development, lens design, and the manufacturing of contact lenses and care solutions. Menicon's entities in the EEA are located in the Netherlands, France, Germany, Italy, and Spain.
Menicon uses PFAS to manufacture RGP contact lenses in the EU. PFAS are present as a raw material and as a part of a mixture intended for polymerisation used for manufacturing RGP lenses. The proposed PFAS restriction would consequently affect RGP contact lenses and RGP LCPs.
Menicon needs 10 to 13 years to place a new RGP product on the market if it includes developing a new material. However, all the RGP projects accomplished by Menicon up to now have been based on availability of fluorinated compounds. If there is no derogation for PFAS use in RGP contact lenses, it is difficult to predict how long a quest for substitution will take.
Menicon asked FINDEST, a company specialized in AIenabled technologies/innovations scouting, to conduct an artificial intelligence (AI) study, with the goal to identify potential alternatives. The goal of the AI study was to identify alternative materials based on key material requirements of the PFAS compound.
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The analysis of alternatives concludes that no viable substitute is available now or will be available in the foreseeable future. The AI search specially designed to explore all available scientific literature and patents for a possible substitution did not reveal newly appeared options which would be worth investigating at the current stage.
As a consequence, in the most likely "nonuse" scenario, Menicon will have no other option but to halt the production and imports of RGP lenses in the EEA. This is because the PFAS used are integral components for the lens blanks that are used to manufacture RGP contact lenses. The market for RGP contact lenses will therefore become minimal and have no prospects for the future as a consequence of a PFAS ban.
A potential broad restriction would have disproportionate socioeconomic implications on the EEA RGP contact lens industry. Overall, the total impact of a PFAS restriction is monetized as more than 50 M EUR for Menicon, including 5 to 10 M EUR of social impacts from unemployment in the EEA, 5 to 10 M EUR of substitution costs, and 30 to 40 M EUR of economic impacts (EBIT loss). This is a conservative estimate (lower bound), based on the understanding that this is not the sole injury likely to be suffered in the EEA. The market share covered by this impact assessment is approximately 40% of the whole EEA RGP contact lens market. The market share of 40% is a highlevel estimation based on approximations made by industry professionals; there is no data available about the size of the niche RGP contact lens market. Based on this, we conservatively decide to not use this percentage to extrapolate the economic and social impacts to the EEA market.
A potential PFAS restriction would affect the distribution of Menicon's goods and would therefore also affect Menicon's distributors and downstream customers, which are located in other EEA countries. Menicon's entities in the EEA have 20,000 to 25,000 downstream customers that purchase RGP contact lenses (containing PFAS) or LCPs for RGP contact lenses. In addition, there would likely be a negative impact on investments in R&D and on the competitiveness of the contact lens market in the EEA.
The qualityoflife reductions for RGP contact lens users would be large in case of a potential PFAS restriction. A large group of RGP contact lens users with specific medical and eye conditions, such as myopia, hyperopia, presbyopia, and astigmatism, would be adversely affected in case of a potential PFAS restriction. A large group of current users cannot switch to alternatives such as soft lenses because they do not sufficiently correct visual acuity.
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Annex I - List of standards and regulations applicable to RGP contact lenses and products targeted by the potential PFAS restriction
Medical Devices Directive
93/42/EEG 2017/745
Medical Device Directive Medical Device Regulation
Quality Management System
NENENISO 13485:2016/A11:2021 Medical devices - Quality Management systems
ISO Guide 13485:2017
Medical devices - Practical guide
Risk management
NENENISO 14971:2019/A11:2021 Medical devices - Application of risk management to medical devices
NPRCENISO/TR 24971:2020 Medical devices - Guidance on the application of ISO14971
MEDDEV's
MEDDEV 2.1/1 MEDDEV 2.4/1 rev.9
Definition "medical devices" Guidelines for the classification of medical devices
Incoming inspection
ISO 28591:1999
Sampling procedures for inspection by attributes Part 1: Sampling schemes indexed by acceptance quality limit (AQL) for lotbylot inspection
Clinical evaluation / clinical investigation
NENENISO 11980:2012 NENENISO 14155:2011 MEDDEV 2.7.1 rev.4
Ophthalmic optics - Contact lenses and contact lens care products - Guidance for clinical investigations Clinical investigation of medical devices for human subjects - Good clinical practice Clinical evaluation: guide for manufacturers and notified bodies
Labeling and information
NENENISO152231:2021
NENENISO20417:2021 NENENISO 11978:2017/
Medical Devices - Symbols to be used with medical device labels, labeling and information to be supplied - Part 1: General requirements Information supplied by the manufacturer of medical devices
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Amd 1:2020
Ophthalmics optics - Contact lenses and contact lens care products - labelling
Shelf life
NENENISO 11987:2012
Ophthalmic optics - Contact lenses - Determination of shelflife
Contact lenses general
NENENISO 14534:2015
Ophthalmic optics Contact lenses and contact lens care products
Fundamental requirements
NENENISO 183691:2017 (cor. 201801)
Ophthalmic optics - Contact lenses - Part 1:
Vocabulary, classification system and
recommendations for labeling specifications -
Amendment 1
NENENISO 183692:2017 Ophthalmic optics - Contact lenses - Part 2: Tolerances
NENENISO 183693:2017 (cor. 201801)
Ophthalmic optics - Contact lenses - Part 3:
Measurement methods
NENENISO 183694:2017 (cor. 201801)
Ophthalmic optics - Contact lenses - Part 4:
Physicochemical properties of contact lens materials
Compatibility of contact lenses
NENENISO 11981:2017
Ophthalmic optics - Contact lenses and contact lens care products - Determination of physical compatibility of contact lens care products with contact lenses
Biological evaluation
NENENISO 109931:2018 NENENISO 109933:2014 NENENISO 109935:2009 NENENISO 1099310:2013 NENENISO 1099311:2018 NENENISO 1099318:2009
Biological evaluation of medical devices - Part 1: Evaluation and testing Biological evaluation of medical devices - Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity Biological evaluation of medical devices - Part 5: Tests for in vitro Cytotoxicity Biological evaluation of medical devices - Part 5: Tests for irritation and delayed type hypersensitivity Biologische evaluatie van medische hulpmiddelen Deel 11: Beproevingen op systematische toxiciteit Biologische evaluatie van medische hulpmiddelen Deel 18: Chemische karakterisering van materialen
Trial lenses
NPR ISO/ TS 19979:2018
Ophthalmic optics - Contact lenses - Hygienic management of Multi patient use trail contact lenses
Sterility
NENENISO 116071:2020
Packaging for terminally sterilized medical devices -
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NENENISO 116072:2020 NENENISO 117371:2018 NENENISO 176651:2006
Part 1: Requirements for materials, sterile barrier systems and packaging systems Packaging for terminally sterilized medical devices - Part 2: Validation requirements for forming, sealing and assembly processes Sterilisatie van medische hulpmiddelen Microbiologische methodes Deel 1: Bepaling van de populatie van microorganismen op producten Sterilisatie van producten voor de gezondheidszorg Stoom Deel 1: Eisen voor de ontwikkeling, validatie en routine controle van een sterilisatieproces voor medische hulpmiddelen
Cleanrooms
ENISO 14644 - 1:2016 ENISO 14644 - 2:2016
Cleanrooms and associated controlled environments Cleanrooms
Vigilance
MEDDEV2.121 rev.8
Guidelines on a medical devices vigilance system
Usability
NENENIEC 623661:2020
Medical devices - Part 1: Application of usability engineering to medical devices
Internal audits
NENENISO 19011:2018
Guidelines for auditing management systems
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Annex II - Overview of the key studies on gaspermeability in contact lenses
In 1987 Bergenske and Polse proved that refitting longtime wearers of hard (PMMA) lenses with RGP lenses brought corneal touch threshold back to normal levels within a few weeks61. Long term wear of hard (PMMA) contact lenses decreases corneal sensitivity, and it was a big concern at the time. Corneal sensitivity measurements were conducted over a 6month period in this study, and its results suggested an oxygen dependency factor in the control of corneal sensitivity accompanying contact lens wear.
In 1994 and 1995 Giasson and Bonanno conducted invivo and invitro experiments with rabbits, studying corneal acidosis.62,63 This condition occurs in contact lenses wearers and render the eye more susceptible to infection, stromal ulceration, perforation, scarring, and significant vision loss. They found that the fluorinecontaining RGP lenses induced less endothelial acidification than PMMA lenses. These studies confirmed that increasing the oxygen permeability of lenses reduced the harm to the epithelium.
The 1994 invivo study investigated the effects of anoxia, carbon dioxide retention, and contact lens gas transmissibility on the epithelial and aqueous humor pH in living rabbits. The key conclusion was that increasing lens oxygen transmissibility via transition to a new lens material decreased epithelial acidification, pointing at a way to minimize cellular complications arising from contact lens wear. Polymethylmethacrylate (PMMA) lens wear acidified epithelial cells by preventing CO2 efflux and by inducing hypoxia. After initiation of rigid, gaspermeable (RGP) lens wear or CO2air exposure, pHi dropped transiently and then recovered partially. This recovery of pHi was not observed during anoxia, whether induced by PMMA lens wear or exposure to 100% N2. The aqueous humor also acidified during PMMA lens wear; a phenomenon not observed during RGP lens wear. Changes in aqueous pH were smaller, slower, and delayed when compared to their epithelial counterparts.
The invitro study conducted in 1995 tested whether lens wear can cause endothelial acidosis. Rabbit corneas were isolated and perfused in vitro. The endothelial intracellular pH (pHi) was measured with a pH sensitive fluorescent probe (BCECF). Three conditions were examined: 1) Polymethylmethacrylate (PMMA) and rigid gaspermeable (RGP) contact lens wear using a range of oxygen transmissibility (Dk/L) from 0 to 121, 2) epithelial hypoxia produced by exposure to oligomycin/sodium azide solution
61 Bergenske PD, Polse KA. The effect of rigid gas permeable lenses on corneal sensitivity. J Am Optom Assoc. 1987 Mar;58(3):2125. PMID: 3471806. https://pubmed.ncbi.nlm.nih.gov/3471806/
62 Giasson C, Bonanno JA. Acidification of rabbit corneal endothelium during contact lens wear in vitro. Curr Eye Res. 1995 Apr;14(4):3118. doi: 10.3109/02713689509033531. PMID: 7606917. https://pubmed.ncbi.nlm.nih.gov/7606917/
63 Giasson C, Bonanno JA. Corneal epithelial and aqueous humor acidification during in vivo contact lens wear in rabbits. Invest Ophthalmol Vis Sci. 1994 Mar;35(3):85161. PMID: 8125748. https://pubmed.ncbi.nlm.nih.gov/8125748/
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or epithelial perfusion with 100% N2 equilibrated Ringer's solution, and 3) epithelial exposure to Ringer's equilibrated with 5% CO2, balance air. PMMA and RGP contact lens wear acidified endothelial cells by 0.23 +/ 0.01 (n = 23) and 0.11 +/ 0.01 pH units (n = 23), respectively, within twenty min of lens insertion. Epithelial hypoxia, induced by sodium azide and oligomycin, reversibly acidified the endothelium by 0.04 +/ 0.01 pH units (n = 4). However, epithelial hypoxia induced by perfusion with 100% N2 equilibrated Ringer's did not have a significant effect on endothelial pHi. Introduction of 5% CO2 to the epithelium, acidified the endothelium by 0.15 +/ 0.02 pH units (n = 7) within 10 min. The overall conclusion was that contact lens wear can significantly acidify corneal endothelial cells, which is caused almost exclusively by a buildup of CO2 behind the lens. As expected, RGP contact lenses induced less endothelial acidosis than PMMA controls.
In 1986 Swedish scientists Rengstorff and Odby conducted a study of Paraperm EW, a rigid gas permeable material with a Dk of 56 X 10(11) manufactured into contact lenses (please note the Menicon Z material has a Dk of 163).64 One hundredfive patients were fitted including three patients with aphakia, seven with keratoconus and 17 with astigmatism of 2.5 D or more. In this initial study of adaptation, these lenses were worn on a daily basis with a 95% success rate. Over onethird of the patients were previously unsuccessful with PMMA, other rigid gaspermeable lenses (with a lower Dk), or soft lenses. Complications such as corneal staining (7%) and lens coating (9%) were all reversible. The results during a threemonth period showed a high success rate for daily wear and a favorable potential for extended wear. Their conclusion was that a high Dk ensured initial comfort, quick adaptation and minimal complications.
In 1999 Ren et al. studied the relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa, the most common bacterium from the group of Preudomonas, which might cause serious infections, to human corneal epithelial cells after overnight and extended wear.65 They found that oxygen permeability level, and not the type of lens, was critical for reducing bacterial adherence to exfoliated surface epithelial cells.
The study was designed as a 3year, prospective, randomized, masked clinical trial to evaluate the relationship of contact lens oxygen transmissibility and bacterial adherence to exfoliated surface epithelial cells in human overnight and extended lens wearers in a single center; corneal cell desquamation rate, surface epithelial cell size, and tear lactate dehydrogenase (LDH) levels were also determined concurrently. One hundred nine human volunteers were successfully fit with test lenses prospectively and completed this study. Seven soft and three rigid gas permeable (RGP) lenses with stratified oxygen transmissibility were evaluated.
Bacterial binding was determined by measuring Pseudomonas aeruginosa (PA) adherence to exfoliated corneal epithelial cells. The number of exfoliated cells with adherent bacteria were counted using
64 Rengstorff RH, Odby A. Adaptation to Paraperm extended wear lenses: a clinical study in Sweden. J Am Optom Assoc. 1986 Aug;57(8):6003. PMID: 3462240. https://pubmed.ncbi.nlm.nih.gov/3462240/ 65 Ren DH, Petroll WM, Jester JV, HoFan J, Cavanagh HD. The relationship between contact lens oxygen permeability and binding of Pseudomonas aeruginosa to human corneal epithelial cells after overnight and extended wear. CLAO J. 1999 Apr;25(2):80100. Erratum in: CLAO J 1999 Jul;25(3):175. PMID: 10344294. https://pubmed.ncbi.nlm.nih.gov/10344294/
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fluorescence microscopy. The effects of contact lens wear on the corneal surface were further assessed by alterations in tear LDH, and by surface epithelial cell size and epithelial thickness using in vivo tandem scanning confocal microscopy (TSCM). Baseline values of outcome measures served as controls for individual patients; a concurrent group of controls were also followed to monitor seasonal or possible individual fluctuations.
Quantitative evidence demonstrated that lens physical oxygen transmissibility properties and not lens type significantly correlated inversely with binding of PA to human exfoliated corneal epithelial cells after overnight and extended wear (R=0.258, P=0.0084); there was a significant decrease in surface epithelial cell desquamation and a significant increase in surface cell size following wear for all test lenses (P<0.05). Epithelial thinning was also observed following lens wear (P<0.05). Thus, for the first time a significant correlation was established between contact lensinduced increases in epithelial PA binding and lens oxygen transmissibility in humans. Ultraoxygen (as of 1999 state of play) permeable test lenses did not appear to increase bacterial binding over individual control levels; all test lenses suppressed surface epithelial cell shedding.
An earlier study by Ostrem, Fink and Hill in 1996 was done on a small group of humans (six subjects) to determine the effects of rigid contact lens materials of various permeabilities and identical design on the oxygen shortfall of the human cornea and to explore differences in oxygen delivery to the cornea associated with contact lens materials of different modulus of elasticity values. 66 The 6 materials had Dk values that ranged from 0.02 to 127 (cm2/s)(ml O2/ml x mm Hg) and modulus of elasticity values from 1300 to 2200 MPa. They found that the amount of oxygen deficiency in the cornea decreased with the increase in lens transmittance under both static and dynamic conditions, and a significant difference (p < 0.001) was observed between materials.
In 2005 Odenthal et al. published results of a 5year study of longterm changes in corneal endothelial morphology after discontinuation of low gaspermeable contact lens wear. 67 The key conclusion was that endothelial polymegethism and pleomorphism caused by wearing low oxygen permeable PMMA or HEMA contact lenses is partly reversible.
In this study, 66 patients were regularly examined after discontinuation of lowgas permeability contact lenses. Of these, 61 patients switched to RGP or high hydrous SCL and 5 to wear glasses. The mean coefficient of variation of corneal endothelial cell area was 37.5 to 35.7 (P = 0.022), and the mean coefficient of variation of the number of planes was from 13.1 to 12.4 (P = 0.004). The average proportion of hexagonal cells increased from 54.2 to 56.2 (P = 0.013). The morphology of corneal endothelial cells improved markedly with discontinuation of lowgas permeability CL, but their values did not return to the levels observed in nonCL users. Mean endothelial cell density was almost the same as normal agerelated cytoreduction (0.6%/year) in nonCL users.
66 Ostrem ED, Fink BA, Hill RM. Contact lens transmissibility: effects on delivery of oxygen to the cornea. Optom Vis Sci. 1996 Mar;73(3):15963. doi: 10.1097/0000632419960300000006. PMID: 8725016. https://pubmed.ncbi.nlm.nih.gov/8725016/ 67 Odenthal MT, Gan IM, Oosting J, Kijlstra A, Beekhuis WH. Longterm changes in corneal endothelial morphology after discontinuation of low gaspermeable contact lens wear. Cornea. 2005 Jan;24(1):328. doi: 10.1097/01.ico.0000138860.97302.5a. PMID: 15604864. https://pubmed.ncbi.nlm.nih.gov/15604864/
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Annex III - Overview of the key studies on the use of conventional RGP lenses and scleral RGP lenses in patients with corneal issues
As early as in 1989, Mannis et al. reported that in the early stages of keratoconus, visual correction with glasses was possible, but in moderate to advanced stages, the role of glasses is limited and contact lenses may be necessary for visual correction.68
In 2015 Gomes et al. in their guidelines on keratoconus and ectatic diseases recommended use of RGP lenses as a treatment option for keratoconus patients in all cases of unsatisfactory vision with glasses or conventional soft contact lenses. 69,70 The first choice is a conventional corneal rigid gaspermeable lens. If this fails, other possibilities listed by the guidelines include hybrid lens (rigid center, soft skirt), keratoconus design corneal rigid gaspermeable contact lens, piggyback (a rigid gas permeable lens sitting on top of a soft contact lens), corneoscleral, miniscleral, semiscleral, and scleral lens.71
Van der Worp et al. in their 2004 review of modern scleral contact lenses (ScCLs) stated that ScCLs demonstrated therapeutic potential in their ability to successfully fit most patients with distorted corneas that were intolerant to other forms of vision correction including piggyback, hybrid or corneal gas permeable lenses.72 They are often used as the last resort treatment, and that's why they are also known as "medically necessary contact lenses." The authors of this overview summarized results of a. 70 studies confirming the potential of ScCLs to bring a solution to patients with highly irregular corneas. They also concluded that use of ScCLs positively impacts healthcare costs, because it allows to delay or prevent corneal surgery. For instance, Tan et al. showed that 69% of their 517 eyes fitted with ScCL had previously failed with other contact lenses; most of these patients would probably have been referred for a corneal transplant.73
68 Mannis, Mark J. MD; Zadnik, Karla OD. Contact Lens Fitting in Keratoconus. CLAO Journal 15(4):p 282289, October 1989. 69 Gomes, Jos A. P. MD, PhD; Tan, Donald MD, PhD; Rapuano, Christopher J. MD; Belin, Michael W. MD; Ambrsio, Renato Jr MD, PhD; Guell, Jos L. MD; Malecaze, Franois MD, PhD; Nishida, Kohji MD; Sangwan, Virender S. MD the Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global Consensus on Keratoconus and Ectatic Diseases. Cornea 34(4):p 359369, April 2015. | DOI: 10.1097/ICO.0000000000000408 70 Ectatic corneal disease (ECD) or corneal ectasia is a group of progressive eye disorders characterised by thinning and bulging of the cornea, and can result in moderate to severe impairment of vision. 71 All scleral lenses are larger than conventional RGP lenses. Corneoscleral and semi-scleral lenses rest near the junction between the cornea and the sclera. Mini scleral lenses rest on the anterior sclera, and scleral lenses, which are the largest variety, rest on the outer sclera.
72 Eef van der Worp, Dina Bornman, Daniela Lopes Ferreira, Miguel FariaRibeiro, Nery GarciaPorta, Jos M. GonzlezMeijome, Modern scleral contact lenses: A review, Contact Lens and Anterior Eye, Volume 37, Issue 4, 2014, Pages 240250, ISSN 13670484, https://doi.org/10.1016/j.clae.2014.02.002. 73 Tan DT, Pullum KW, Buckley RJ. Medical applications of scleral contact lenses: 1. A retrospective analysis of 343 cases. Cornea. 1995 Mar;14(2):1219. PMID: 7743792.
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The figure below represents a (full) scleral lens and demonstrates how it might be used to fit an irregular cornea.
A recent study by Ozek et al. evaluated the use of ScCLs in a total of 58 eyes of 40 patients with keratoconus (46 eyes), keratoglobus (4 eyes), and postkeratoplasty astigmatism (8 eyes).74 They found that the mean logMAR uncorrected visual acuity (UCVA), bestcorrected visual acuity (BCVA) with glasses, and BCVA with scleral lenses were 0.91 0.21 (range 0.401.80), 0.57 0.12 (range 0.101.80), and 0.16 0.02 (range 0.001.30), respectively. BCVA with scleral lenses was significantly higher than UCVA and BCVA with glasses (p<0.05). The mean values of uncorrected contrast sensitivity, contrast sensitivity with glasses, and contrast sensitivity with scleral lenses were 0.97 0.12 (range 0.301.65), were 1.16 0.51 (range 0.301.80), and 1.51 0.25 (range 0.901.80), respectively. Contrast sensitivity with scleral lenses was significantly higher than uncorrected and with glasses (p<0.05). Furthermore, the National Eye Institute Visual Functioning Questionnaire (NEIVFQ 25), which evaluates QOL related to vision, showed a significant improvement in the overall score after scleral lens wear compared to before (p<0.05).
ScCL's other proven use is for treating severe dry eye. In 2021 Moon et al. did a clinical trial of Large Diameter Scleral Lenses on Asian patients with severe ocular surface disease who had uncorrected visual acuity of less than 0.3 logMAR but more than 0.3 logMAR of best corrected visual acuity (BCVA) and had them wear Large Diameter Scleral Lenses for 12 weeks.75 The subjects included a total of 21 eyes (13 patients) with persistent epithelial defects in 10 eyes, graft versus host disease in 6 eyes, StevensJohnson syndrome in 4 eyes, and severe dry eye in 1 eye. At 12 weeks of wearing the Large Diameter Scleral Lenses, BCVA improved from 0.77 logMAR to 0.27 logMAR (P < 0.001). The proportion of highgrade corneal and conjunctival fluorescein staining decreased from 61.90% to 14.29% and from 52.38% to 9.52%, respectively (both P = 0.0036 and 0.0063, respectively). OSDI and NEIVFQ25 improved from 67.89 to 34.69 and from 51.40 to 64.48, respectively (both P < 0.001).
74 Ozek D, Kemer OE, Altiaylik P. Visual performance of scleral lenses and their impact on quality of life in patients with irregular corneas. Arq Bras Oftalmol. 2018 Nov./Dec.;81(6):475480. doi: 10.5935/00042749.20180089. Epub 2018 Sep 13. PMID: 30231157. 75 Moon J, Lee SM, Hyon JY, Kim MK, Oh JY, Choi HJ. Large diameter scleral lens benefits for Asians with intractable ocular surface diseases: a prospective, singlearm clinical trial. Sci Rep. 2021 Jan 27;11(1):2288. doi: 10.1038/s4159802182010z. PMID: 33504920; PMCID: PMC7840975.
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In an earlier interventional study by Jacobs and Rosenthal, 33 posttransplant patients with severe dry eye due to chronic graftversushost disease, that did not respond to conventional therapy, were fitted with Boston Scleral Lens Prosthetic Device (BSLPD).76 Almost all patients experienced improvement in pain, photophobia, and overall quality of life, with over half (52%) reporting the highest level of improvement in pain and over twothirds (73%) reporting the highest level of improvement in quality of life. For reading and driving, over 90% of patients reported improvement, with over 60% reporting the highest level of improvement in each of these activities.
In 2013 Dimit et al. analysed the use of a scleral device (Prosthetic Replacement of the Ocular Surface Ecosystem PROSE) by 51 patients over a period ranging from several weeks to several years.77 The most common reasons for using the device were moderate to severe dry eye syndrome (n=25), refractive issues (n=23, with keratoconus being the most common at n=14), and other abnormalities (n=3). All patients reported improvement. he bestcorrected visual acuity (logMAR) improved with PROSE device use in both the dry eye group (from 0.51 to 0.16, p=0.091) and the refractive group (from 0.41 to 0.21, p=0.1514).
In 2005 a study by Domingez et al. demonstrated that RGP lenses could significantly improve visual acuity in cases of Pellucid marginal degeneration, a progressive form of corneal disease that causes the cornea to thin and bulge.78 The researchers fitted Bitoric gaspermeable contact lenses on 11 patients with Pellucid marginal corneal degeneration (PMCD). The uncorrected visual acuity (logMAR) was 0.957 +/ 0.398 (Snellen 20/181), the bestcorrected spectacle visual acuity (logMAR) was 0.231 +/ 0.309 (Snellen 20/34), and the contact lenscorrected visual acuity (logMAR) was 0.0424 +/ 0.06275 (Snellen 20/22). The corrected visual acuity of eyes with PMCD improved by about 2 lines with the use of Bitoric RGP compared to the use of spectacles.
For postsurgery patients, according to Steele's and Davidson's 2007 review, specialty RGP lenses typically present the only effective choice in cases where vision correction is necessary, such as after refractive corrective surgery.79 Soft contact lenses or conventional RGP lens designs are effective when a small amount of tissue is removed, and in other, more complicated cases, large diameter RGP lenses, reverse geometry lenses, or scleral lenses may be appropriate. For example, in cases where the corneal shape is highly irregular and conventional RGP lenses do not fit well, scleral lenses are easier to fit because they are supported by the sclera.
Tan et al. in 2010 also concluded that reverse geometry RGP lenses with the design based on individual topographic data can improve visual performance of postLASIK eyes by reducing higher order
76 Jacobs DS, Rosenthal P. Boston scleral lens prosthetic device for treatment of severe dry eye in chronic graft versushost disease. Cornea. 2007 Dec;26(10):11959. doi: 10.1097/ICO.0b013e318155743d. PMID: 18043175. 77 Dimit R, Gire A, Pflugfelder SC, Bergmanson JP. Patient ocular conditions and clinical outcomes using a PROSE scleral device. Cont Lens Anterior Eye. 2013 Aug;36(4):15963. doi: 10.1016/j.clae.2013.02.004. Epub 2013 Mar 15. PMID: 23499361. 78 Dominguez CE, Shah A, Weissman BA. Bitoric gaspermeable contact lens application in pellucid marginal corneal degeneration. Eye Contact Lens. 2005 Sep;31(5):2413. doi: 10.1097/01.icl.0000156221.47633.1f. PMID: 16163019. 79 Steele C, Davidson J. Contact lens fitting postlaserin situ keratomileusis (LASIK). Cont Lens Anterior Eye. 2007 May;30(2):8493. doi: 10.1016/j.clae.2006.12.005. Epub 2007 Feb 27. PMID: 17329148.
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aberrations.80 After lens wear, 28 subjects had an increase in visual acuity by one Snellen line (from 0.90 +/ 0.33 to 1.11 +/ 0.24), and significant improvements were observed in all symptoms (reduced night vision, glare, halos, and monocular diplopia). Highorder aberrations, including spherical aberration, coma aberration, thirdorder aberration, and fourthorder aberration, were reduced by more than 70%. The customized lenses fit well for all subjects.
80 Tan G, Chen X, Xie RZ, He H, Liu Q, Guo Y, Liao A, Zhong X. Reverse geometry rigid gas permeable contact lens wear reduces highorder aberrations and the associated symptoms in postLASIK patients. Curr Eye Res. 2010 Jan;35(1):916. doi: 10.3109/02713680903421186. PMID: 20021249.
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