Discussion Points for Expansion of the "Checklist of Information Usually Submitted in an Investigational Device Exemption (IDE) Application for Refractive Surgery Lasers" Draft Document

Comments and suggestions regarding this draft document should be submitted within 30 days of the above release date to Morris Waxler, Ph.D., Division of Ophthalmic Devices, 9200 Corporate Boulevard (HFZ 460), Rockville, MD 20850. Comments and suggestions received after this date may not be acted upon by the Agency until the document is next revised or updated. For questions regarding this draft document, contact Everette T. Beers, Ph.D. at (240) 276-4200 or by e-mail at everette.beers@fda.hhs.gov.

The following proposed revisions in Food and Drug Administration (FDA) guidance on refractive surgery lasers will be discussed at a public hearing on October 21, 1997. The objective is to extend this guidance to high myopia, astigmatism, and hyperopia based on current scientific and clinical knowledge. Other modifications also are proposed.

HIGH MYOPIA AND HYPEROPIA WITH AND WITHOUT ASTIGMATISM

The proposed inclusion and exclusion criteria for study of the "normal" population as well as safety and effectiveness target values are summarized in the tables below.

PROPOSED MODIFICATIONS TO THE CURRENT LOW TO MODERATE MYOPIA GUIDANCE DOCUMENT

1. In Section 3.2.4.1. , change from "Contact lens wearers should:

   1. remove soft or gas permeable contact lenses two weeks prior to baseline measurements

   2. remove hard contact lenses three weeks prior to baseline measurements, and have two central keratometry readings and two manifest refractions taken at least one week apart that do not differ by more than 0.50 diopter in either meridian; mires should be regular."

      To: "Contact lens wearers should remove soft or gas permeable contact lenses at least three days prior to baseline measurements. At that exam cycloplegic and manifest refractions as well as corneal topography should be obtained on both eyes. If the investigator determines that the topography is within normal limits, surgery may be scheduled at least one week after the initial exam, with no contact lens wear permitted prior to the surgery. If, on the day of scheduled surgery for the primary eye, central keratometry readings and manifest refraction spherical equivalents do not differ significantly from the initial exam measurements (by more than 0.50 diopter for low to moderate myopia and hyperopia, or by more than 1.0 diopter for high myopia), surgery can proceed. If the refractive change exceeds this criterion, the surgery should be rescheduled after refractive stability is achieved.

      For fellow eyes, contact lens wear is permitted until at least three days prior to surgery. If, on the day of scheduled surgery for the fellow eye, central keratometry readings and manifest refraction spherical equivalents do not differ significantly from the initial exam measurements (by more than 0.50 diopter for low to moderate myopia and hyperopia, or by more than 1.0 diopter for high myopia), surgery can proceed. If the refractive change exceeds this criterion, the surgery should be rescheduled after refractive stability is achieved."

2. In Section 3.2.4., add the following language: "If there are scientific reasons for expecting different safety and effectiveness results based on gender or race, these demographic variables should be studied."
3. In Section 3.2.4.2., change "History of glaucoma or an intraocular pressure > 21 mm of Hg." To: "History of glaucoma or glaucoma suspect."
4. Section 3.2.1., delete "Haze beyond 6 months with loss of greater than 2 lines of BSCVA should occur in less than 1.0% of subjects"
5. Section 3.2.1., change "Measurement of endothelial cell loss is not necessary as long as laser refractive surgery is 250microns from the corneal endothelium and the laser parameters (e.g., wavelength and fluence) used are unlikely to damage the endothelium from this distance." To: "Endothelial cell loss is an additional safety endpoint that needs to be evaluated when laser refractive surgery is performed closer than 200 microns from the corneal endothelium or the laser parameters (e.g., wavelength and fluence) used are likely to damage the endothelium."
6. Change the Examination Schedule Table from the one in Appendix A to the revised table below.

7. Section 3.2.6.1., change

   "E. Epithelium in the interface (LASIK only)
   F. Lost, misplaced or misaligned flap (LASIK only)
   G. Melting of the flap (LASIK only)
   H. Uncontrolled IOP with increase of >5.0 mm HG above baseline, and any reading above 25.0 mm Hg"

   To:

   "E. Epithelium in the interface with loss of 2 lines (10 letters) or more BSCVA (LASIK only)
   F. Miscreated flap (lost, incomplete, too thin, ) (LASIK only)
   G. Melting of the flap (LASIK only)
   H. Uncontrolled IOP with increase of >10 mm HG above baseline, and any reading above 25 mm Hg"

8. In Section 3.2.6.2., change

   "H. Flap is not of the size and shape as initially intended or microtome stopped in mid-cut (LASIK only)"

   To:

   "H. Misaligned flap (LASIK only)"

9. In Sections 3.2.1. and 3.2.2., change "These endpoints and target values are based primarily on recommendations of the Ophthalmic Devices Panel. However, these endpoints and values are only guidance." To: "Endpoints and target values should be evaluated following the primary treatment plus all planned enhancements. These endpoints and target values are based primarily on recommendations of the Ophthalmic Devices Panel. However, these endpoints and values are only guidance."

ASTIGMATISM ISSUES FOR DISCUSSION

1. Is vector analysis needed for all eyes treated for astigmatism, or only for eyes with BSCVA loss or complications?
2. For eyes treated for astigmatism, what effectiveness criteria are needed in addition to those recommended for other indications? Should effectiveness criteria include both vector analysis and absolute magnitude with axis shift? How should these data best be presented? Is the following example an optimal categorization of clinically relevant data?

REVISED TABLES FOR ALL INDICATIONS

1. Contact lens wearers should remove soft or gas permeable contact lenses at least three days prior to baseline measurements. At that exam cycloplegic and manifest refractions as well as corneal topography should be obtained on both eyes. If the investigator determines that the topography is within normal limits, surgery may be scheduled at least one week after the initial exam, with no contact lens wear permitted prior to the surgery. If, on the day of scheduled surgery for the primary eye, central keratometry readings and manifest refraction spherical equivalents do not differ significantly from the initial exam measurements (by more than 0.50 diopter for low to moderate myopia and hyperopia, or by more than 1.0 diopter for high myopia), surgery can proceed. If the refractive change exceeds this criterion, the surgery should be rescheduled after refractive stability is achieved.

   For fellow eyes, contact lens wear is permitted until at least three days prior to surgery. If, on the day of scheduled surgery for the fellow eye, central keratometry readings and manifest refraction spherical equivalents do not differ significantly from the initial exam measurements (by more than 0.50 diopter for low to moderate myopia and hyperopia, or by more than 1.0 diopter for high myopia), surgery can proceed. If the refractive change exceeds this criterion, the surgery should be rescheduled after refractive stability is achieved.

2. If subjects with latent hyperopia of 0.75 D or greater are to be studied, they should be given the opportunity to participate in a contact lens trial to determine their tolerance to correction of full cycloplegic error while not under cycloplegia. The informed consent document should specify that future retreatment may be necessary if only the manifest refractive error is corrected.

LM = Low to Moderate Myopia (less than or equal to 7D SE) with/without astigmatism
HM = High Myopia (greater than 7D SE) with/without astigmatism
HP = Hyperopia with/without astigmatism

1. The same parameters are to be measured at each examination performed until re-epithelialization occurs.
2. The final exam should be conducted at least three months after the time when refractive stability is achieved. IDE studies for new indications (e.g., hyperopia and high myopia) should initially be proposed for 24 months follow-up, with the option to shorten follow-up time if satisfactory stability can be demonstrated earlier.
3. If the visual acuity with spectacle correction is ³2 lines below that obtained preoperatively, a hard contact lens over refraction should be performed to determine the effect of irregular astigmatism and to estimate the best possible corrected visual acuity.
4. Manifest refractions for hyperopia should be conducted using a standard procedure that "pushes plus", i.e., maximizes the hyperopic correction acceptable to the subject.
5. To be performed for contact lens wearers (see note 1 under inclusion criteria).
6. The slit lamp exam should include a complete survey of the anterior segment. The cornea should be examined in detail with specific recordings and gradings ( 0 to 4+ scale, 0=clear) of the following information: overall corneal clarity, any abnormalities such as corneal infiltrates, opacities in the lamellar bed and density of the scar around the edge of the flap (for LASIK).
7. Pupil size should be assessed under dim conditions at the preop exam and one of the following: following discontinuation of steroids, at time of stability or final exam.
8. Pachymetry, keratometry and axial length should be assessed on all eyes preoperatively and if needed to assess anomalous results in the postoperative course
9. Topography should be performed at the pre-op exam and at the time of anticipated stability.
10. The questionnaire should be administered at the preop exam, at the time of anticipated stability and at the final exam. It should include questions regarding mesopic conditions (including but not limited to night driving). The analysis of study results should attempt to correlate haze to problems identified by subjects under mesopic conditions.

1. If the visual acuity with spectacle correction is ³2 lines below that obtained preoperatively, a hard contact lens over refraction should be performed to determine the effect of irregular astigmatism and to estimate the best possible corrected visual acuity.
2. The slit lamp exam should include a complete survey of the anterior segment. The cornea should be examined in detail with specific recordings and gratings ( 0 to 4+ scale, 0=clear) of the following information: overall corneal clarity, any abnormalities such as corneal infiltrates, opacities in the lamellar bed and density of the scar around the edge of the flap (for LASIK).
3. Pupil size should be assessed whenever VA measurement is done
4. Pachymetry, keratometry and axial length should be assessed on all eyes preoperatively and if needed to assess anomalous results in the postoperative course
5. The questionnaire should include questions regarding mesopic conditions (including but not limited to night driving). The analysis of study results should attempt to correlate haze to problems identified by subjects under mesopic conditions."