GROUP 6 : INTRAOCULAR LENS IMPLANT Amir Mustakim Ab Rashid Nurdania Abd Rahman Nur Nadhirah Abdul Hamid Keerthana a/p Rangasamy

REPORTS & PASSING VALUES PRESENTATION OUTLINE 1 STANDARDS 2 TESTS SETUP 3 TESTING REQUIREMENTS 4 REPORTS & PASSING VALUES

1. REFERENCE FOR STANDARDS DOCUMENTS

IOL Standards All iols are class 3 medical devices requiring premarket approval (PMA) Currently approved IOL’s 3 multifocals 1 accommodating 4 toric 2 phakic

Premarket Approval (PMA) Application requesting clearance to market Class III devices are subjected to Premarket Approval Application needs to contain sufficient valid scientific evidence to provide reasonable assurance that the device is safe and effective for its intended use.

Safety and effectiveness Determination Consideration : -intended population -Conditions of use for the device -benefits to health vs injury or illness from use -Reliability of the device Based only on valid scientific Evidence

Ophthalmic Standards FDA refer to American National Standards Institute (ANSI) and International Standards Organization(ISO) ANSI/ISO provide recommendations on the preclinical requirements and clinical study design (Monofocal, MIOL, PIOL)

IOLS Standards Preclinical requirement : - ISO 11979-2,3,5,6,8 -ANSI Z80-7,12,13 Clinical Recommendations : -Monofocal IOL (ANSI Z80.7, ISO 11979-7) -Multifocal IOL ( ANSI Z80.12, ISO 11979-9) -Phakic IOL ( ANSI Z80.13, ISO 11979-10)

ISO 11979-2:2014 Specifies requirements and test methods for certain optical properties of intraocular lenses (IOLs) with any of spherical, aspheric, monofocal, toric, multifocal, and/or accommodative optics. Publication Date : 2014-08

ISO 11979-3:2006 specifies requirements and test methods for certain mechanical properties of intraocular lenses (IOLs). It is applicable to all types of IOLs intended for implantation in the anterior segment of the human eye, excluding corneal implants, provided that the test method is appropriate to the particular IOL design. Publication Date : 2006-05 Revised : 2012

ISO 11979-5:2006 Specifies particular requirements for the biocompatibility evaluation of materials for intraocular lenses (IOLs) including the processing conditions to produce them. These requirements include evaluation of physicochemical properties that are relevant to biocompatibility. It also gives guidance on conducting an ocular implantation test. Publication Date : 2006-06

ISO 11979-6:2014 specifies tests by which the shelf-life of sterile intraocular lenses (IOLs) in their final packaging can be determined. These tests include procedures to establish the stability of IOLs in distribution and storage. Publication Date : 2014-10

ISO 11979-7 specifies particular requirements for clinical investigations for posterior and anterior chamber intraocular lenses (IOLs). Publish Date : 2014-09 Revised Date : 2018

ISO 11979-8:2017 specifies fundamental requirements for all types of intraocular lenses intended for surgical implantation into the anterior segment of the human eye excluding corneal implants and transplants. Publication date : 2017-04

ISO 11979-9:2006 applicable to any intraocular lens whose optic provides two or more rotationally symmetric powers and whose primary indication is the correction of aphakia with the added benefit of useful vision at more than one distance (e.g. far and near). Publish Date : 2006-09 Revised Date : 2018

ISO 11979-10:2006 applicable to any intraocular lens (IOL) whose primary indication is the modification of the refractive power of a phakic eye but excludes phakic IOLs (PIOLs) that utilize multifocal or other simultaneous vision optics to address presbyopic loss of accommodation and PIOLs that correct astigmatism. Publish Date : 2006-08 Revised Date : 2018

ANSI Z80.7 Applies to the Physical & Mechanical Requirements, Optical Requirement & Biocompatibility and Chemical Testing Requirements of Intraocular Lenses. Publish Date : July 2013

ANSI Z80.12 applies to any ocular implant whose primary indication is the correction of aphakia Implant whose optic is designed to provide simultaneous distance and near vision. For the purposes of this standard, these implants are referred to as multifocal intraocular lenses (MIOLs). This standard does not consider optics designed to provide astigmatic power correction Publish Date : 2007-03

ANSI Z80.13 This standard applies to any intraocular lens (IOL) whose primary indication is the modification of the refractive power of a phakic eye. It does not include IOLs used to correct presbyopia or astigmatism. Publish Date : 2007-03

2. TESTING

BIOCOMPATIBILITY TEST : HYDROLYTIC STABILITY TEST ISO 11979-5:2006 The purposed is to determine the stability of the IOLmaterials in an aqueous environment through detection and quantiication of possible degradation products from hydrolysis and changes in physical appearance, optical properties, and chromatographic characteristics. Procedure: Place the test material in glass containing a aqueous medium Then, incubate at a temperature that is appropriate for the test material and place in the incubator After the test period, the material being removed from the solvent. The exposure medium is qualitatively and quantitatively analyzed for any chemical entities The IOL is then examined by light microscopy, at 10x or higher, and by scanning electron microscopy, at 500x or higher Optical transmittance spectra in the ultraviolet and visible spectral regions, dioptric power, and refractive index are assessed

BIOCOMPATIBILITY TEST : Nd-YAG LASER EXPOSURE TEST TEST ISO 11979-5:2006 To determine the physical and chemical effects of Nd-YAG laser exposure on the IOL To assure that the Nd-YAG laser treatment commonly given to patients with implanted IOLs does not cause leakage of toxic substances Procedure: immerse the IOL in 2ml physiological saline solution and expose to 50 single pulses from the Nd-YAG laser, set an energy level of 5 mJ Focus the laser on the posterior surface of the IOL Refocus the laser for each pulse, distribute the spots evenly over the central 3 mm of the IOL optic Remove the IOL from the solution and collect the exposure media for the analysis

MECHANICAL TEST : DYNAMIC FATIGUE DURABILITY TEST ISO 11979-3:2012 Fatigue testing is carried out by compressing the IOL to a specified dimension and giving cyclic compressive loading to the loop Apparatus used : Clamp Testing plate; flat surface, produced from a low-friction material to minimize haptic frictional constraint Compression device; capable of producing 250 000 cycles of near-sinusoidal compressive loading with a peak-to-peak displacement of 0,5 mm perpendicular to the testing plate

compression corresponds to the line which bisects the angle of contact Arrangement of the apparatus Procedure Clamp the body so that the optical axis is parallel to the testing plate and the line of compression corresponds to the line which bisects the angle of contact Compress the IOL to the appropriate dimension. Perform the cyclic compression on the haptic for 250 000 cycles at ± 0,25 mm around the compression distance. Check whether the loop has broken

MECHANICAL TEST : LOOP STRENGTH TEST ISO 11979-3:2012 Determination of maximum force sustainable in tension collinear with the loop at its junction with the optic Apparatus : Tensometer capable of measuring force with a resolution accuracy of + 0,01 N and capable of producing extension rates between 1 mm/min and 6 mm/min Procedure Clamp the optic so that the direction of pull is tangential to the loop at the loop/optic junction Set the extension rate in the range between 1 mm/min and 6 mm/min and activate the tensometer. Pull the IOL until the loop breaks or separates from the optic, or until the pull force reaches 0,25 N. Discard results if the loop breaks in the clamp

Direction of pull

3. MINIMUM TESTING REQUIREMENTS

1. Dynamic Fatigure Durability Each haptic loop must be durable All loops are required to be capable of withstanding, without breaking, 250, 000 cycles of near sinusoidal deformation of ± 0.25 mm around a compressed distance The compression frequency must be within 1-10 Hz. Tested in IOLs intended for capsular bag placement by clamping an IOL cneter that is 5.0 mm away, compressed, from a testing plate. The flat-surfaced testing plate must be produced from a low-friction material to minimize haptic frictional constraint. To pass, no tested loop must break

2. Recovery of Properties Following Simulated Surgical Manipulation IOLs that intended to be folded or compressed during implantation must still meet manufacturing specifications after deformation. This is tested in 10 lenses of each of the dioptric powers with the smallest and largest cross-sectional dimentions. Folding instructions supplied by the manufacturer are followed, with the lens deformed 3-20 min. After release from the deformed state, the lenses must relax at in situ conditions for up to 24 ± 2h. They are then tested for dioptric power, image quality, overall diameter and sagittal, and surface and bulk homogeneity. To pass, all lenses must remain within manufacturer specifications (ISO, 2006a)

3. Hydrolytic Stability Implanted IOLs must remain stable over time. IOL is exposed to simulated conditions that approximate five years in an aqueous environment of 35 ± 2 ⁰C. After test period, the exposure medium is qualitively and quantively analysed for any chemical entities. The IOL is then examined by light microscopy, at 10× or higher, and by scanning electron microscopy, at 500× or higher. Optical transmittance spectra in the ultraviolet and visible spectral regions, dioptric power, and refractive index are also assessed. To pass, significant differences in the exposure medium and IOL must not be detected

4. Effect of Nd-YAG Laser Exposure When posterior capsule opacification occurs, a Nd-YAG laser may be used to restore vision by creating a hole or an optical path through the lens capsule. Because an IOL may be nicked by the laser, no cytotoxic substances may be released after Nd-YAG laser exposure. To test this requirement, each of five sterile, finished IOLs is immersed in an optical cuvette containing 2 mL physiological saline. Each is then exposed to 50 single laser pulses, set at an energy level of 5 mJ. The laser is focused on the posterior surface of the IOL and refocused for each pulse. Spots should be distributed evenly over the central 3 mm of the IOL optic. The exposure media for all five lenses is pooled and tested for cytotoxicity, according to ISO 11979, as described in  Chapter 6 (ISO, 2006b).

5. Biocompatibility Test ISO 11979-5:2006 Part 5: Biocompatible (ISO, 2006b) Bicompatible test includes — the effects on cell growth and cell damage; — genotoxicity; — local effects after implantation; — sensitization potential.

4. PASSING VALUES FOR TESTING

Standard Values of Test Hydrolytic Stability Test The IOL material was found to be stable in an aqueous environment for 5 years. Optical transmittance curves of the test material in the ultraviolet and visible spectral regions (UV/Vis) shall be recorded before and after hydrolysis testing. Dynamic Fatigue Test

Biocompatibility Test

Nd-YAG Laser Treatment Laser Exposure Test Nd-YAG Laser Treatment The physiological saline surrounding the IOLs shall be analysed for released additives and, also, shall show no Cytotoxicity Test the physiological saline solution for cytotoxicity after Nd-YAG laser treatment