Phakic IOL Standards
Two standards currently exist that describe preclinical and clinical assessments of phakic intraocular lenses – ANSI Z80.13 and ISO 11979-10. These standards are virtually identical. FDA has recognized ISO 11979-10 and is in the process of recognizing ANSI Z80.13.
These standards require the following preclinical testing of phakic IOLs:
Shelf-life and transport stability testing.
Both of these standards require performance of a clinical investigation of the phakic IOL and each include an informative annex that describes the main elements of a clinical investigation that would fulfill the requirements of these standards.
The clinical investigation recommended in the annex is non-controlled with a minimum duration of three years. This minimum study duration is necessary to evaluate endothelial cell density changes and the rate of cataract development. To minimize the risks to the subjects in the study, it is recommended that the study be phased in with 10 subjects followed for 6 months, then 100 additional subjects followed for 6 months, before the rest of the subjects are implanted. The total recommended sample size for the investigation is 300.
The primary endpoint is endothelial cell density (ECD). It is recommended that, at time of implantation, subjects in the study have a minimum ECD of 2,000 to 2,800 depending on age in order to increase the probability of the subject having adequate ECD in the later years of their life.
The following preoperative/postoperative examinations are recommended:
1. Distance uncorrected visual acuity (UCVA)
2. Distance best spectacle-corrected visual acuity (BSCVA)
3. Near visual acuity (VA) with distance spectacle correction
4. Manifest refraction
5. Cycloplegic refraction
6. Axial length
7. Anterior chamber depth
8. Intraocular pressure
9. Slit lamp exam
10. Mesopic pupil size
11. Status of crystalline lens
12. Gonioscopic exam
13. Fundus exam with dilated pupil
14. Pachymetry of corneal thickness
16. Specular microscopy
17. Subject questionnaire
The subject questionnaire should be validated and include questions about glare, halos, double vision, night driving, spectacle/contact lens use, and the time of onset of any visual symptoms. Examples of these types of questionnaires provided in the standard are listed below.
VITALE, S., SCHEIN, O.D., MEINERT, C.L. and STEINBERG, E.P. The Refractive Status and Vision Profile. Ophthalmology, 107, 2000, pp. 1529-1539
P.J., MANGIONE, C., LEE, P., LINDBLAD, A.S., SPRITZER, K.L.,
Two substudies are proposed for the investigation of the phakic IOL:
· Contrast sensitivity – performed on 61 subjects at the pre-operative, 6 and 36 month evaluation to assess contrast sensitivity losses that may be associated with the phakic IOL.
· Clinical clearance analysis – performed on all subjects in Phase 1 of the study (10) to determine the clearances between the Phakic IOL and the ocular tissue.
The standard recommends that multiple safety and effectiveness analyses be performed on the data from the investigation.
Some important safety analyses that are proposed include:
1. Rate of endothelial cell density change
2. Rate of cataract development
3. Percentage of eyes who lose two or more lines of BSCVA
4. Percentage of eyes that have induced manifest refractive astigmatism of greater than 2 D of cylinder
Some important effectiveness analyses that are proposed include:
1. Percentage of eyes that achieve predictability of the Manifest Refraction Spherical Equivalent (MRSE) of ± 1 D
2. Percentage of eyes that achieve predictability of the MRSE of ± 0.5 D
3. Mean change in MRSE between visits (paired analysis)
4. Percentage of eyes that achieve an UCVA of 0.5 or better (for eyes with BSCVA of 1.0 or better preoperatively and targeted for emmetropia)
5. Percentage of eyes that achieve UCVA equal to or better than preoperative BSCVA (for eyes targeted for emmetropia)
These standards specifically require the labeling to contain the following clinical information:
Ø a summary of the clinical results of the investigation;
Ø any recommendations for periodic evaluations after implantation (based on the risk analysis and/ or any clinical investigation performed);
Ø any restrictions in the indications for use if necessitated by the anatomical clearance analysis and clinical evaluation (e.g., anterior chamber depth).