The American National Standard for Ophthalmics — Laser Systems for
One standard currently exists that describes pre-clinical and clinical assessments of refractive laser systems: ANSI Z80.11-2007 — Laser Systems for Corneal Reshaping. This standard was created with input from industry, professional groups, academia, and government experts. FDA is in the process of recognizing this ANSI standard. The standard can be recognized in its entirety, in part, or with specific additions. Any recommendations made by the Panel members will be considered in our recognition evaluation of this standard.
The pre-clinical portion of the standard has laser safety requirements for:
• Protection against contaminants
• Protection against toxins and allergens
• Photobiological hazards
• Thermal hazards
• Mechanical hazards
• Electrical safety
• Radiation safety
• Light hazards
• Gas safety (for gas lasers)
• Safety in use
It also describes appropriate methods for system alignment, fail-safe monitoring, and laser system calibration, control, and performance. An informative annex provides information on characterization of laser ablation beams and treatment patterns.
ANSI Z80.11 calls for patient enrollment to occur in stages for a new laser system for which there is no prior clinical data.
An informative annex provides guidance concerning clinical studies designed to demonstrate the safety and effectiveness of a refractive laser system. This section recommends that for a new laser system without prior clinical data, the study should have a sample size adequate to detect adverse events with an expected frequency of 1% or greater. In order to attain this goal, there should be 300 eyes in the study. This is based upon the following statistical considerations:
§ If the true population rate of a given type of event is ≥1%, then we have 95% confidence that at least 1 such event will occur in the clinical study.
§ Conversely, if no events of a given type occur, we can be 95% confident that the true rate is <1%.
The standard suggests a single-group, prospective study. There is no control arm; each eye’s preoperative status serves as its own control for effectiveness considerations. The standard states that a clinical study should have a duration of 24 months, but that it can be terminated early, if refractive stability is demonstrated; subjects should be followed to a time point at least three months past the point of refractive stability. Patient visits are recommended preoperatively, on the day of surgery, and at the following times postoperatively: day 1, week 1, month 1, month 3, month 6, month 9, month12, and month 24.
The clinical annex recommends that the following data be collected on all subjects:
§ Uncorrected Visual Acuity (UCVA);
§ Best Spectacle Corrected Visual Acuity (BSCVA);
§ Manifest and cycloplegic refractions;
§ Subject questionnaire;
§ Intraocular pressure;
§ Slit lamp exam;
§ Dilated fundus exam;
§ Mesopic pupil size;
§ Pachymetry (preoperatively);
§ Topography ;
§ Keratometry (preoperatively).
A contrast sensitivity sub-study should be performed:
(1) when features of the laser beam raise concerns that there may be visual performance losses not correctable by spectacles; or
(2) when the manufacturer wishes to justify softening or deleting precautionary labeling statements concerning reductions in visual performance under poor lighting.
If a contrast sensitivity sub-study is done, then:
• Testing should be performed under mesopic conditions.
• Testing should be done at spatial frequencies close to 1.5, 3, 6, and 12 cycles/degree.
• Subjects should be tested with their best spectacle correction preoperatively and postoperatively.
The standard recommends many analyses to assess treatment stability, effectiveness, and safety.
In determining whether stability has been reached, it should be considered whether the following have been established:
• 95% of eyes are changing by ≤ 1D in manifest refraction between visits;
• The mean refraction is changing at a rate of ≤ 0.50 D per year;
• The rate of refractive change is decreasing over time;
• The refractive change is not statistically different from zero (95% confidence interval does not include zero);
• Stability is confirmed at a visit at least 3 months after the proposed point of stability.
In evaluating effectiveness, both the predictability (accuracy of correction) and uncorrected visual acuity should be considered.
For predictability the analyses should look at the percentage of eyes:
• that achieve accuracy of the Manifest Refraction Spherical Equivalent (MRSE) within
§ ±0.50 D
§ ±1.00 D
§ ±2.00 D;
• that are over-corrected by
§ >1.00 D
§ >2.00 D;
• that are under-corrected by
§ >1.00 D
§ >2.00 D;
• that achieve accuracy of Sphere (to Target) and Cylinder (to zero) components within
§ ± 0.50 D
§ ± 1.00 D.
For uncorrected visual acuity (UCVA) outcomes, the analyses should evaluate the percentage of eyes:
• that achieve a UCVA of
§ 20/40 or better
§ 20/20 or better
• that achieve a UCVA equal to or better than the preoperative Best Spectacle Corrected Visual Acuity (BSCVA)
In evaluating safety, the following analyses are recommended:
• The percentage of eyes that lose 2 lines or more of BSCVA;
• The percentage of eyes with BSCVA worse than 20/40 (for eyes with BSCVA of 20/20 or better pre-op);
• The percentage of eyes that have an increase of refractive astigmatism of greater than 2.00 D as compared to the preoperative refraction;
• The rates of adverse events (e.g., significant diffuse lamellar keratitis, corneal ulcers, significant flap problems, corneal edema at ≥ 1 month postop, epithelial defects at ≥ 1 month).
• Contrast sensitivity changes should be evaluated, if this type of study was done.
• Subject symptoms should be evaluated.
A subject questionnaire should be administered to all subjects. Validated questionnaires are recommended. Survey instruments should include questions regarding:
§ double vision,
§ spectacle/contact lens use,
§ night driving,
§ satisfaction with the surgery, and
§ spectacle independence.
The rating system used in the questionnaire should be well characterized. Results from the questionnaire should be used to assess the incidence of clinically significant symptoms, the change in symptoms from preop, satisfaction, and independence from the need for visual correction (spectacles or contact lenses).
The ANSI Standard for Laser Systems for Corneal Reshaping has created a consensus basic structure for clinical and pre-clinical studies of Laser Systems for Corneal Reshaping. It includes comprehensive evaluations of a number of important effectiveness and safety parameters, including ratings of subjective symptoms.