[Federal Register Volume 61, Number 47 (Friday, March 8, 1996)]
[Proposed Rules]
[Pages 9373-9377]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-5445]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 886
[Docket No. 93P-0277]
Ophthalmic Devices; Reclassification of Neodymium:Yttrium:
Aluminum:Garnet (Nd:YAG) Laser for Peripheral Iridotomy
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule; notice of panel recommendation.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
reclassify the ophthalmic neodymium:yttrium:aluminum:garnet (Nd:YAG)
laser (mode-locked or Q-switched) intended for peripheral iridotomy
from class III (premarket approval) into class II (special controls).
The agency is also issuing for public comment the recommendation of the
Ophthalmic Devices Panel (the Panel) regarding the reclassification of
this device. The Panel made this recommendation after reviewing the
reclassification petition submitted by Intelligent Surgical Lasers,
Inc. (ISL). FDA is also issuing for public comment its tentative
findings on the Panel's recommendation and its intent to change the
generic designation of the device from Nd:YAG laser for posterior
capsulotomy to Nd:YAG laser for posterior capsulotomy and peripheral
iridotomy. After considering any public comments on the Panel's
recommendation and FDA's tentative findings, FDA will approve or deny
the reclassification petition by order in the form of a letter to the
petitioner. FDA's decision on the petition will be announced in the
Federal Register. If the petition is approved and the device is
reclassified into class II, FDA will publish a final rule to codify the
reclassification.
DATES: Written comments by June 6, 1996.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Morris Waxler, Center for Devices and
Radiological Health (HFZ-460), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850, -301-594-2018.
SUPPLEMENTARY INFORMATION:
I. Introduction
On March 2, 1993, ISL submitted a petition under section 513(f)(2)
of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C.
360c(f)(2)), requesting that the ophthalmic Nd:YAG laser (mode-locked
or Q-switched) intended for peripheral iridotomy be reclassified from
class III into class II.
The subject device is automatically classified into class III under
section 513(f)(1) of the act because it is not within a type of device
that was introduced or delivered for introduction into interstate
commerce for commercial distribution before May 28, 1976, it is not
substantially equivalent to such a device, and it is not substantially
equivalent to a device placed in commercial distribution since May 28,
1976, which was subsequently reclassified into class II or class I.
Section 513(f)(2) of the act provides that FDA may initiate the
reclassification of a device classified into class III under section
513(f)(1) of the act, or the manufacturer or importer of the device may
petition the agency to reclassify the device into class I or class II.
FDA's regulations in 21 CFR 860.134 set forth the procedures for filing
and review of a petition to reclassify these class III devices. In
order to reclassify the ophthalmic Nd:YAG laser (mode-locked or Q-
switched) for peripheral iridotomy into class II, it is necessary that
the proposed new class has sufficient regulatory controls to provide
reasonable assurance of the safety and effectiveness of the device for
its intended use.
II. Background
Nd:YAG lasers originally were developed for industrial
applications, and were successfully employed in such industries as
watchmaking prior to the initiation of clinical trials in Europe and
the United States. Therefore, the basic principles of operation of the
device
[[Page 9374]]
were scientifically established well before any clinical testing of the
device in ophthalmic surgery. -
Surgical iridectomies, i.e., manual surgical excisions of part of
the iris, were performed, with mixed results, in the late 1800's to
relieve the symptoms of glaucoma. In 1920, the differences between the
various types of glaucoma were described and it then became apparent
why the surgery relieved the symptoms of some patients and not others.
As a result, peripheral surgical iridectomies were then performed only
on patients with pupillary-block (angle-closure) glaucoma.
Argon laser iridotomies, surgery with an argon laser to create an
iris hole, became the preferred treatment for most cases of angle-
closure glaucoma in the 1970's. Although there were advantages to the
use of argon lasers (reduced risk of flat chamber, wound leak,
endophthalmitis, malignant glaucoma, and lens subluxation), there were
different complications associated with the new modality (permanent
corneal burns, retinal burns, iritis, localized cataract formation,
posterior synechiae, failed patency, intraocular pressure (IOP) rises
and iris pigmentation).
The next treatment modality, iridotomy with the Q-switched Nd:YAG
laser, was introduced during the early 1980's to treat angle-closure by
a mechanical cutting effect to create peripheral iridotomies rather
than the thermal effect of argon lasers. Because the technology
permitted tissue disruption through a transparent medium with
negligible heat generation, the Nd:YAG laser appeared to be ideal for
ophthalmic surgery on opacified posterior capsular membranes, thus
avoiding the risks involved in traditional invasive surgery as well as
the thermal effects characteristic of other ophthalmic laser devices.
Clinical trials were conducted and, subsequently, FDA granted premarket
approval for three CooperVision Nd:YAG lasers (models 2000 and 2500 in
1985; model 2300 in 1986) for discission of the posterior capsule of
the eye (posterior capsulotomy).
On January 24, 1986, the Medical Laser Manufacturers Association
(MLMA) submitted to FDA, under section 513(e) of the act and 21 CFR
860.120, a petition for a change in the classification of the
ophthalmic Nd:YAG laser (mode-locked or Q-switched) intended for
posterior capsulotomy. On February 20, 1986, the MLMA amended its
petition to include section 513(f)(2) of the act and 21 CFR 860.134 of
the regulations as a basis for its requested relief. The petition
requested that the ophthalmic Nd:YAG laser (mode-locked or Q-switched),
intended for posterior capsulotomy, be reclassified from class III into
class II. FDA referred the petition to the Panel for its recommendation
as to whether the device should be reclassified. On May 22, 1986,
during an open public meeting the Panel recommended that FDA reclassify
the device from class III into class II when intended for use in
posterior capsulotomy. The Panel identified the following devices as
examples of the generic type of device: The Meditec OPL-3, the M-Tec
2000, the Horizon 2000, the Horizon 2500, and the YAG-100.
The Panel also recommended that this generic type of device be
identified as the ``Nd:YAG laser for posterior capsulotomy.'' On
December 14, 1987 (52 FR 47454), FDA published in the Federal Register
a notice announcing the Panel's recommendation. On March 31, 1988, FDA
ordered (by letter to MLMA) the reclassification of the Nd:YAG laser
intended for posterior capsulotomy and substantially equivalent devices
of this generic type from class III into class II.
On March 2, 1993, ISL submitted to FDA, under section 513(f) of the
act, a petition requesting reclassification of the ophthalmic Nd:YAG
laser (mode-locked or Q-switched) intended for peripheral iridotomy
from class III into class II (Ref. 1). The agency referred the petition
to the Panel for its recommendation on the requested change in
classification.
III. Recommendation of the Panel
The Panel met on October 28, 1993, in an open public meeting to
discuss the subject device. After considering the published studies,
published data on laser parameters for safe and effective Nd:YAG
iridotomy, and the guidelines for laser iridotomy published by the
American Academy of Ophthalmology (Ref. 2), the Panel recommended that
the ophthalmic Nd:YAG laser (mode-locked or Q-switched) intended for
peripheral iridotomy be reclassified from class III into class II. The
Panel believed the petitioners had presented sufficient data to
demonstrate that special controls can be established to provide
reasonable assurance of the safety and effectiveness of the device for
its intended use. The Panel also noted that the procedure is well
understood and widely used by most ophthalmologists in the United
States, as evidenced by the discussion of the Panel members (Ref. 3 p.
83).
IV. Device Description
The ophthalmic Nd:YAG laser intended for peripheral iridotomy
consists of a mode-locked or Q-switched solid state Nd:YAG laser that
generates short pulse, low energy, high power, coherent optical
radiation. When the laser output is combined with focusing optics, the
high irradiance at the target site causes tissue disruption via optical
breakdown. A visible aiming system is utilized to target the invisible
Nd:YAG laser radiation on or in close proximity to the target tissue.
A. Principles of Operation
The Nd:YAG laser is one component of a device system that also
includes conditioning optics, a delivery system, an aiming system, and
operator controls. Its laser beam must be shaped by conditioning optics
to a configuration with a specific profile and desired characteristics.
The physical properties of the Nd:YAG laser beam that directly
influence the ability of the device to perform its intended function
safely and effectively are its invisible infrared beam at a wavelength
of 1,064 nanometers, output pulse generating method, output energy,
pulse width, spatial mode, convergence angle, spotsize, and pulse
repetition frequency. The only variable that is selected by the
ophthalmic surgeon during the iridotomy procedure is the device's
output energy.
While other types of lasers (e.g., the argon laser) used for
ophthalmic surgery employ long duration exposures to achieve thermal
tissue effects for photocoagulation, tissue cutting, or tissue
destruction, the ophthalmic Nd:YAG laser (mode-locked or Q-switched)
intended for peripheral iridotomy uses very short duration exposures
(pulses) that are focused precisely to small spot sizes and that
produce a high local irradiance (power density). The combination of
short exposure duration and high irradiance results in nonlinear
absorption of the radiation by the target tissue, causing tissue
disruption through optical breakdown. The plasma generated by the
process of optical breakdown provides protection for posterior tissue
in direct line with the incident beam. These unique characteristics
permit the ophthalmic Nd:YAG laser to perform a patent iridotomy with
reduced inflammation, regardless of iris pigmentation.
B. Device Specifications
Mode-locked laser output consists of a train of 7 to 10 pulses with
a pulse duration of about 30 nanoseconds and a pulsewidth of about 30
picoseconds. Q-switched laser output consists of single pulses, with
pulsewidths of about 2 to 20 nanoseconds in duration.
[[Page 9375]]
The typical threshold of optical breakdown of tissue in air for
mode-locked lasers is 1014 watts per centimeter squared, and for
Q-switched lasers is 1011 watts per centimeter squared. The
threshold for optical breakdown of tissue in an aqueous environment
appears to be lower but varies depending upon the nature of the tissue.
For disruption of the iris of the eye, an energy setting of 4.0 to 6.0
millijoules results in optical breakdown creating the desired tissue
effect after application of 1 to 4 bursts that contain 1 to 4 pulses/
burst (Refs. 10, 11, 12, 13, 14, and 15).
In addition to the laser, the other two main components of the
system subject to the petition are a visible light beam aiming system
and a slit-lamp biomicroscope used by the operator to target the
treatment laser beam and to visually monitor the treatment process.
V. Summary of Reasons for the Recommendation
The Panel based its recommendation on the data and information
contained in the petition and presented during the open committee
discussion during the Panel meeting on October 28, 1993. After review
and consideration of the available information, the Panel gave the
following reasons in support of its recommendation to reclassify the
generic type ophthalmic Nd:YAG laser (mode-locked or Q-switched)
intended for peripheral iridotomy from class III into class II:
(1) The device is not an implant.
(2) General controls by themselves are insufficient to provide
reasonable assurance of the safety and effectiveness of the device.
(3) There is sufficient publicly available information to establish
special controls to assure the performance of the device for its
intended use. Also, there is sufficient publicly available information
to demonstrate that the risks to health have been determined, and that
the relationship between the device's performance parameters and risks
and its safety and effectiveness have been established by valid
scientific evidence.
(4) Various safety features of medical lasers are already
controlled by existing FDA standards (21 CFR 1040.10 and 1040.11)
promulgated under the Radiation Control for Health and Safety Act of
1968 (42 U.S.C. 263b).
The Panel believed that the following devices identified in the
petition are representative of the generic type of device: the NIDEK
YAG-100; the NIDEK 200; the Coherent 9900; and the Meridian LASAG MR-2.
VI. Risks To Health
Based on publicly available information establishing that it can
successfully perform a discission of the iris (iridotomy), the Panel
concluded that the ophthalmic Nd:YAG laser (mode-locked or Q-switched)
intended for peripheral iridotomy is effective for its intended use.
The Panel also determined that the foreseeable risks to health
associated with the device are related to either unintentional damage
to nontarget tissue or postoperative complications resulting from user
error or device malfunction. These risks include corneal damage or
edema, iritis, corectopia, lenticular opacities, retinal damage,
transient elevation of IOP, failure to obtain iridotomy, precipitation
of angle-closure attack, late closure of iridotomy, and iris atrophy.
The risks of these adverse effects have been documented to be low and
acceptable when the device is used in accordance with its directions
and appropriate postoperative care is followed.
The use of the Nd:YAG laser for peripheral iridotomy may be
contraindicated for patients without a clear cornea or aqueous,
patients with chronic uveitis, patients with a tendency to bleed,
patients on anticoagulant therapy, and patients with a glass
intraocular lens.
VII. Summary of Data Upon Which the Recommendation is Based
During its review and discussion of the petition, the Panel paid
close attention to the risks associated with the use of the device. The
clinical studies included in the petition reported few risks to health,
and the few that were reported were clearly identified. The Panel
concluded that special controls can be established to provide
reasonable assurance of the safety and effectiveness of the device when
intended for peripheral iridotomy. The incidence rates of iridotomy
closure, vision loss due to progression of laser induced lens or
corneal damage, additional filtration surgery, transient iris bleeding,
transient IOP spike, focal lens opacities, nonprogressive corneal
endothelial changes, retinal damage, focal corneal opacities, mild
iritis, and hyphema associated with Nd:YAG laser iridotomy are either
lower than those for argon laser surgery or conventional surgical
iridotomy or are self-limiting and not persistent.
Del Priore, et al. (Ref. 4) compared iridotomies using the Nd:YAG
laser and argon laser in a prospective, randomized clinical study. The
study focused on 43 patients (86 eyes) followed for 20 months (mean
followup time 27 7 months). The mean preoperative visual
acuity in the argon treated and the Nd:YAG treated eyes was 6/12
3 Snellen lines and did not change postoperatively. No
retinal detachments or laser burns of the macula were detected.
Iridotomy closure was not observed in any of the Nd:YAG laser treated
eyes, but 9 (21 percent) argon iridotomies required retreatment. Visual
loss due to progression of laser induced lens or corneal damage was not
observed in any eye. Nine of 43 (21 percent) argon laser treated eyes
and 8 of 43 (19 percent) Nd:YAG laser treated eyes required laser
trabeculoplasty for further intraocular pressure lowering after
iridotomy. Transient iris bleeding was encountered in 19 (44 percent)
Nd:YAG laser treated eyes, but was not seen in any argon treated eyes.
Six (32 percent) of the eyes with transient bleeding had IOP elevations
greater than 10 millimeters (mm) Hg within the first 3 hours, and the
IOP spike was greater than 20 mm Hg in four (17 percent) of these eyes.
Focal opacification of the anterior lens capsule was seen in 23 (53
percent) argon laser treated eyes and none of the Nd:YAG laser treated
eyes. This difference is statistically significant (P<0.01). focal="" corneal="" endothelial="" opacities="" were="" encountered="" in="" 13="" (30="" percent)="" nd:yag="" laser="" treated="" and="" 11="" (26="" percent)="" argon="" laser="" treated="" eyes.="" neither="" type="" of="" opacity="" enlarged="" clinically,="" and="" both="" tended="" to="" regress.="" clinically="" significant="" corneal="" edema="" or="" corneal="" decompensation="" did="" not="" develop="" in="" the="" eyes="" of="" either="" treatment="" group="" during="" long="" term="" followup.="" although="" several="" different="" nd:yag="" lasers="" (am="" yag-100="" (american="" medical="" optics),="" coherent="" jk="" nd:yag,="" and="" coherent="" 9900)="" were="" used="" in="" the="" study,="" no="" differences="" were="" indicated="" by="" the="" results.="" the="" nd:yag="" laser="" offers="" intraoperative="" advantages="" in="" patients="" who="" cannot="" maintain="" a="" steady="" head="" position="" and="" fixation,="" and="" is="" independent="" of="" iris="" color.="" the="" nd:yag="" laser="" is="" also="" regarded="" as="" the="" treatment="" of="" choice="" in="" most="" patients="" with="" chronic="" pupillary-block="" glaucoma="" (ref.="" 4).="" in="" other="" studies,="" fleck,="" et="" al.="" (ref.="" 5)="" compared="" nd:yag="" laser="" iridotomy="" with="" and="" without="" argon="" laser="" pretreatment="" and="" concluded="" that="" argon="" laser="" pretreatment="" offers="" no="" advantage="" over="" primary="" nd:yag="" laser="" iridotomy.="" on="" the="" other="" hand,="" goins,="" et="" al.="" (ref.="" 6)="" found="" that="" argon="" laser="" pretreatment="" significantly="" reduced="" the="" incidence="" of="" hemorrhage="" during="" nd:yag="" iridotomy="" (p="0.012)." robin="" and="" pollack="" (ref.="" 7)="" found="" that="" hyphema="" is="" not="" clinically="" significant="" when="" eyes="" are="" pretreated="" with="" the="" argon="" laser.="" of="" the="" nd:yag="" [[page="" 9376]]="" iridotomies="" they="" studied,="" 67="" percent="" (8/12)="" had="" operative="" hemorrhages,="" while="" 17="" percent="" (2/12)="" of="" the="" argon="" pretreated="" eyes="" had="" hemorrhages.="" robin="" and="" pollack="" (ref.="" 7)="" also="" reported="" a="" lower="" incidence="" of="" bleeding="" when="" eyes="" were="" pretreated="" with="" the="" argon="" laser.="" mcgalliard="" and="" wishart="" (ref.="" 8)="" studied="" 81="" eyes="" with="" shallow="" anterior="" chambers="" and="" raised="" iop.="" iridotomies="" were="" performed="" to="" prevent="" further="" angle="" closure="" glaucoma="" (acg)="" and="" to="" remove="" pupillary="" block="" that="" could="" have="" contributed="" to="" the="" raised="" iop.="" in="" eyes="" where="" there="" was="" no="" peripheral="" anterior="" synechia="" (pas)="" there="" was="" no="" drop="" in="" iop,="" but="" in="" eyes="" with="" well="" established="" pas="" 69="" percent="" showed="" a="" drop="" in="" iop.="" jiang="" (ref.="" 9)="" also="" found="" a="" very="" significant="" difference="" between="" the="" preoperative="" values="" and="" the="" postoperative="" values="" at="" 3-year="" followup.="" in="" a="" study="" of="" 31="" patients="" (40="" eyes="" with="" persistent="" angle="" closure="" glaucoma="" (pacg)),="" the="" iridotomy="" controlled="" the="" iop,="" and="" the="" iridotomy="" hole="" closed="" spontaneously="" in="" four="" eyes.="" the="" success="" rates="" were="" 94="" percent="" at="" 6="" months,="" 91="" percent="" at="" 2="" years,="" and="" dropped="" to="" 82.4="" percent="" at="" the="" end="" of="" the="" third="" year.="" romano,="" et="" al.="" (ref.="" 10)="" compared="" nd:yag="" iridotomy="" with="" conventional="" surgical="" iridectomy.="" they="" found="" that="" in="" the="" nonlaser-treated="" group,="" pilocarpine="" alone="" controlled="" the="" iop.="" in="" the="" laser="" treated="" group,="" eyes="" without="" pas="" required="" fewer="" medications="" to="" maintain="" normal="" pressures="" than="" eyes="" with="" pas="" required.="" regarding="" nd:yag="" laser="" technique,="" march="" (ref.="" 11)="" recommends="" that="" a="" laser="" lens="" be="" used="" in="" performing="" a="" nd:yag="" laser="" iridectomy="" to="" aid="" in="" the="" placement="" of="" the="" lesion="" on="" the="" iris.="" he="" also="" recommends="" iridectomy="" placement="" beneath="" the="" upper="" lid="" if="" possible="" to="" avoid="" complications="" of="" halos,="" blurring,="" horizontal="" bands="" of="" light,="" and="" diplopia="" secondary="" to="" light="" transmission="" through="" the="" site="" postoperatively.="" focusing="" on="" the="" ability="" of="" the="" nd:yag="" laser="" to="" produce="" a="" patent="" iridotomy,="" spaeth="" (ref.="" 11)="" reviewed="" a="" prospective="" study="" of="" 58="" patients="" in="" which="" the="" right="" eyes="" were="" treated="" with="" the="" lasag="" microruptor="" 2="" nd:yag="" laser="" and="" the="" left="" eyes="" with="" a="" britt="" argon="" laser,="" and="" concluded="" that="" the="" nd:yag="" laser="" can="" indeed="" produce="" a="" patent="" iridotomy.="" he="" observed="" that="" there="" was="" a="" significant="" pressure="" rise="" in="" one="" third="" of="" the="" cases="" treated="" and="" that="" frequent="" hemorrhage="" occurred="" at="" the="" time="" of="" the="" iridectomy,="" but="" was="" not="" so="" severe="" that="" a="" gross="" hyphema="" developed.="" in="" no="" instance="" of="" nd:yag="" laser="" treatment="" was="" corneal="" endothelium="" or="" anterior="" lens="" capsule="" damage="" noted.="" completion="" of="" the="" iridectomy="" was="" made="" on="" the="" basis="" of="" visualization="" of="" the="" lens="" through="" a="" hole="" in="" the="" iris.="" the="" iop="" results="" reported="" for="" both="" lasers="" indicated="" a="" rise="" in="" iop="" at="" 1="" hour="" postoperative="" which="" decreased="" to="" the="" preoperative="" level="" 1="" week="" postoperative.="" in="" two="" studies="" by="" robin="" and="" pollack="" (refs.="" 7="" and="" 12)="" using="" the="" coherent="" 9900="" q-switched="" and="" the="" amo="" yag-100="" lasers,="" the="" authors="" reported="" that="" hyphema="" was="" not="" clinically="" significant="" and="" was="" consistent="" with="" other="" studies="" showing="" a="" lower="" incidence="" of="" bleeding="" for="" pretreated="" argon="" eyes.="" in="" one="" study,="" 33="" eyes="" (both="" brown="" and="" blue="" irises)="" from="" 28="" patients="" with="" pupillary="" block="" glaucoma="" were="" treated.="" study="" followup="" was="" 1="" month.="" twenty-six="" had="" previous="" argon="" laser="" iridectomies.="" all="" had="" iridectomy="" closure="" within="" a="" week="" of="" argon="" treatment="" or="" there="" had="" been="" failure="" to="" penetrate="" the="" iris;="" the="" preoperative="" iop="" range="" was="" 8="" mm="" to="" 74="" mm="" hg="" and="" was="" 10="" mm="" to="" 43="" mm="" hg="" at="" 1-month="" followup.="" complications="" reported="" after="" use="" of="" the="" coherent="" 9900="" q-switched="" nd:yag="" laser="" were="" focal="" discrete="" nonprogressive="" corneal="" endothelial="" changes="" in="" six="" eyes="" (18="" percent),="" bleeding="" in="" 12="" eyes="" (36="" percent),="" and="" iop="" greater="" than="" 10="" mm="" hg="" during="" the="" first="" 3="" hours="" postoperatively="" in="" nine="" eyes="" (27="" percent).="" no="" hyphema,="" laser-induced="" lens="" damage="" or="" retinal="" damage="" was="" observed.="" two="" iridectomies="" closed="" within="" days="" of="" treatment.="" study="" followup="" was="" 1="" month.="" in="" the="" second="" study,="" the="" authors="" studied="" 40="" eyes="" (20="" patients)="" in="" which="" one="" eye="" was="" treated="" with="" an="" argon="" laser="" and="" the="" fellow="" eye="" with="" a="" q-switched="" yag="" laser,="" an="" amo="" yag-100="" (7="" patients)="" or="" a="" coherent="" jk="" prototype="" (13="" patients).="" iris="" colors="" were="" blue="" and="" brown.="" at="" no="" time="" was="" the="" iop="" change="" significant="" between="" the="" argon="" laser="" and="" yag="" laser="" treated="" patients.="" inflammation="" was="" seen="" in="" all="" patients.="" of="" the="" argon="" treated="" eyes,="" 12="" had="" a="" rise="" in="" iop="" during="" the="" first="" 3="" hours="" postoperatively.="" six="" (30="" percent)="" iridectomies="" required="" retreatment,="" focal="" corneal="" opacities="" were="" seen="" in="" five="" (25="" percent)="" of="" the="" argon="" treated="" eyes,="" and="" posterior="" synechiae="" were="" seen="" in="" three="" (15="" percent)="" of="" the="" argon="" treated="" eyes.="" by="" comparison,="" thirteen="" yag="" treated="" eyes="" had="" an="" iop="" rise="" during="" the="" first="" 3="" hours="" and="" bleeding="" occurred="" in="" nine="" (45="" percent),="" with="" one="" having="" less="" than="" 5="" percent="" hyphema="" which="" cleared="" by="" the="" first="" postoperative="" day.="" no="" iridectomy="" closures="" were="" seen,="" while="" focal="" corneal="" opacities="" were="" seen="" in="" seven="" (35="" percent)="" of="" the="" yag="" treated="" eyes.="" none="" of="" the="" yag="" treated="" eyes="" suffered="" focal="" lenticular="" opacity.="" finally,="" the="" panel="" noted="" the="" publication="" by="" the="" american="" academy="" of="" ophthalmology,="" laser="" peripheral="" iridotomy="" for="" pupillary-="" block="" glaucoma="" (ref.="" 2),="" which="" discusses="" surgical="" iridectomy="" and="" laser="" iridotomy="" techniques,="" treatment="" parameters,="" complications="" and="" patient="" care,="" and="" provides="" insight="" in="" addressing="" laser="" iridotomy="" and="" the="" above="" risks.="" the="" panel="" believes="" that="" the="" risks="" identified="" above="" that="" are="" directly="" attributable="" to="" the="" nd:yag="" laser="" for="" peripheral="" iridotomy="" can="" be="" controlled="" by="" special="" controls.="" the="" risks="" of="" damage="" to="" the="" corneal="" endothelium,="" the="" lens,="" or="" the="" retina="" are="" slight.="" these="" risks="" can="" be="" minimized="" by="" ensuring="" proper="" device="" design="" of="" the="" laser="" beam="" for="" accuracy="" and="" precision.="" the="" risk="" of="" iop="" rise="" can="" be="" controlled="" by="" proper="" device="" labeling="" and="" by="" the="" surgeon="" through="" available,="" established="" medical="" procedures="" and="" treatments.="" there="" is="" reasonable="" assurance="" that="" an="" ophthalmic="" nd:yag="" laser="" (mode-locked="" or="" q-switched)="" is="" safe="" and="" effective="" for="" iridotomy="" when="" the="" device="" is="" used="" consistent="" with="" appropriate="" labeling,="" designed="" in="" accordance="" with="" proper="" device="" specifications="" and="" produced="" under="" a="" quality="" assurance="" program="" to="" ensure="" that="" critical="" specifications="" are="" met="" within="" specified="" tolerances.="" viii.="" fda's="" tentative="" findings="" fda="" tentatively="" concurs="" with="" the="" recommendation="" of="" the="" panel="" that="" the="" nd:yag="" laser="" intended="" for="" peripheral="" iridotomy="" should="" be="" reclassified="" into="" class="" ii="" and="" that="" the="" generic="" designation="" of="" the="" device="" be="" changed="" from="" nd:yag="" laser="" for="" posterior="" capsulotomy="" to="" nd:yag="" laser="" for="" posterior="" capsulotomy="" and="" peripheral="" iridotomy.="" the="" agency="" also="" tentatively="" concludes="" that="" ``new="" information''="" in="" the="" form="" of="" publicly="" available,="" valid="" scientific="" evidence="" exists="" to="" provide="" reasonable="" assurance="" of="" the="" safety="" and="" effectiveness="" of="" the="" nd:yag="" laser="" for="" its="" intended="" use.="" consistent="" with="" the="" purpose="" of="" the="" act,="" class="" ii="" controls="" (labeling)="" as="" defined="" by="" section="" 513(a)(1)(b)="" of="" the="" act="" are="" sufficient="" to="" provide="" reasonable="" assurance="" that="" current="" nd:yag="" lasers="" are="" safe="" and="" effective="" for="" their="" intended="" use.="" ix.="" environmental="" impact="" the="" agency="" has="" determined="" under="" 21="" cfr="" 25.24(e)(2)="" that="" thisaction="" is="" of="" a="" type="" that="" does="" not="" individually="" or="" cumulatively="" have="" a="" significant="" effect="" of="" the="" human="" environment.="" therefore,="" neither="" as="" environmental="" assessment="" nor="" an="" environmental="" impact="" statement="" is="" required.="" [[page="" 9377]]="" x.="" analysis="" of="" impacts="" fda="" has="" examined="" the="" impacts="" of="" the="" proposed="" rule="" under="" executive="" order="" 12866="" and="" the="" regulatory="" flexibility="" act="" (pub.="" l.="" 96-354).="" executive="" order="" 12866="" directs="" agencies="" to="" assess="" all="" costs="" and="" benefits="" of="" available="" regulatory="" alternatives="" and,="" when="" regulation="" is="" necessary,="" to="" select="" regulatory="" approaches="" that="" maximize="" net="" benefits="" (including="" potential="" economic,="" environmental,="" public="" health="" and="" safety,="" and="" other="" advantages;="" distributive="" impacts;="" and="" equity).="" the="" agency="" believes="" that="" this="" proposed="" rule="" is="" consistent="" with="" the="" regulatory="" philosophy="" and="" principles="" identified="" in="" the="" executive="" order.="" in="" addition,="" the="" proposed="" rule="" is="" not="" a="" significant="" regulatory="" action="" as="" defined="" by="" the="" executive="" order="" and="" so="" is="" not="" subject="" to="" review="" under="" the="" executive="" order.="" the="" regulatory="" flexibility="" act="" requires="" agencies="" to="" analyze="" regulatory="" options="" that="" would="" minimize="" any="" significant="" impact="" of="" a="" rule="" on="" small="" entities.="" because="" reclassification="" of="" devices="" from="" class="" iii="" into="" class="" ii="" may="" relieve="" manufacturers="" of="" the="" cost="" of="" complying="" with="" the="" premarket="" approval="" requirements="" in="" section="" 515="" of="" the="" act,="" and="" may="" permit="" small="" potential="" competitors="" to="" enter="" the="" marketplace="" by="" lowering="" their="" costs,="" the="" agency="" certifies="" that="" the="" final="" rule="" will="" not="" have="" a="" significant="" economic="" impact="" on="" a="" substantial="" number="" of="" small="" entities.="" therefore,="" under="" the="" regulatory="" flexibility="" act,="" no="" further="" analysis="" is="" required.="" xi.="" request="" for="" comments="" interested="" persons="" may,="" on="" or="" before="" june="" 6,="" 1996,="" submit="" to="" the="" dockets="" management="" branch="" (address="" above)="" written="" comments="" regarding="" this="" proposal.="" two="" copies="" of="" any="" comments="" are="" to="" be="" submitted,="" except="" that="" individuals="" may="" submit="" one="" copy.="" comments="" are="" to="" be="" identified="" with="" the="" docket="" number="" found="" in="" brackets="" in="" the="" heading="" of="" this="" document.="" received="" comments="" may="" be="" seen="" in="" the="" office="" above="" between="" 9="" a.m.="" and="" 4="" p.m.="" monday="" through="" friday.="" xii.="" references="" the="" following="" references="" have="" been="" placed="" on="" display="" in="" the="" dockets="" management="" branch="" (address="" above)="" and="" may="" be="" seen="" by="" interested="" persons="" between="" 9="" a.m.="" and="" 4="" p.m.,="" monday="" through="" friday.="" 1.="" reclassification="" petition="" for="" the="" nd:yag="" laser="" for="" iridotomy,="" submitted="" by="" intelligent="" surgical="" lasers,="" inc.,="" march="" 2,="" 1993.="" 2.="" american="" academy="" of="" ophthalmology="" guideline:="" laser="" peripheral="" iridotomy="" for="" pupillary-block="" glaucoma,="" approved="" by="" board="" of="" directors,="" june="" 25,="" 1988.="" (also="" contained="" in="" the="" petition.)="" 3.="" transcript="" of="" the="" ophthalmic="" devices="" panel="" meeting,="" october="" 28,="" 1993.="" 4.="" del="" priore,="" l.="" v.,="" a.="" l.="" robin,="" and="" i.="" p.="" pollack,="" ``neodymium:yag="" and="" argon="" laser="" iridotomy:="" long-term="" followup="" in="" a="" prospective,="" randomized="" clinical="" trial,''="" ophthalmology,="" 94(9):1205-="" 1211,="" 1988.="" 5.="" fleck,="" b.="" w.,="" e.="" wright,="" c.="" mcglynn,="" ``argon="" laser="" pretreatment="" 4="" to="" 6="" weeks="" before="" nd:yag="" laser="" iridotomy,''="" ophthalmic="" surgery,="" 22(11):644-649,="" 1991.="" 6.="" goins,="" k.,="" e.="" schmeisser,="" t.="" smith,="" ``argon="" laser="" in="" nd:yag="" iridotomy,''="" ophthalmic="" surgery,="" 21(7):497-500,="" 1990.="" 7.="" robin,="" a.="" l.="" and="" i.="" p.="" pollack,="" ``q-switched="" neodymium-yag="" laser="" iridotomy="" in="" patients="" in="" whom="" the="" argon="" laser="" fails,''="" archives="" of="" ophthalmology,="" 104(4):531-535,="" 1986.="" 8.="" mcgalliard,="" j.="" n.,="" p.="" k.="" wishart,="" ``the="" effect="" of="" nd:yag="" iridotomy="" on="" intraocular="" pressure="" in="" hypertensive="" eyes="" with="" shallow="" anterior="" chambers,''="" eye,="" 4(6):823-829,="" 1990.="" 9.="" jiang,="" y.="" q.,="" ``the="" long-term="" effect="" of="" nd:yag="" laser="" iridotomy,''="" chung-hua="" yn="" ko="" tsa="" chih="" chin,="" journal="" of="" ophthalmology,="" 27(4):221-224,="" 1991.="" 10.="" romano,="" j.="" h.,="" r.="" a.="" hitchings,="" and="" d.="" pooinasawmy,="" ``role="" of="" nd:yag="" peripheral="" iridectomy="" in="" the="" management="" of="" ocular="" hypertension="" with="" a="" narrow="" angle,''="" ophthalmic="" surgery,="" 19(11):814-="" 816,="" 1988.="" 11.="" march,="" w.="" f.,="" and="" g.="" spaeth,="" ``yag="" laser="" iridectomy,="" complications,''="" ophthalmic="" lasers="" (a="" second="" generation),="" thorogare,="" new="" york:="" slack="" inc.,="" 1990.="" 12.="" robin,="" a.="" l.="" and="" i.="" p.="" pollack,="" ``a="" comparison="" of="" neodymium:yag="" and="" argon="" laser="" iridotomies,''="" ophthalmology,="" 91(9):1011-1016,="" 1984.="" 13.="" moster,="" m.="" r.,="" et="" al.,="" ``laser="" iridectomy,="" a="" controlled="" study="" comparing="" argon="" and="" neodymium:yag,''="" ophthalmology,="" 93:20-24,="" 1986.="" 14.="" cinotti,="" d.="" j.,="" et="" al.,="" ``neodymium:yag="" laser="" therapy="" for="" pseudophakic="" pupillary="" block,''="" journal="" of="" cataract="" and="" refractive="" surgery,="" 12:174-179,="" 1986.="" 15.="" robin,="" a.="" l.="" et="" al,="" ``q-switched="" neodymium-yag="" iridotomy:="" a="" field="" trial="" with="" a="" portable="" laser="" system,''="" archives="" of="" ophthalmology,="" 104:526-530,="" 1986.="" list="" of="" subjects="" in="" 21="" cfr="" part="" 886="" medical="" devices,="" ophthalmic="" goods="" and="" services.="" therefore,="" under="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" and="" under="" authority="" delegated="" to="" the="" commissioner="" of="" food="" and="" drugs,="" it="" is="" proposed="" that="" 21="" cfr="" part="" 886="" be="" amended="" as="" follows:="" part="" 886--ophthalmic="" devices="" 1.="" the="" authority="" citation="" for="" 21="" cfr="" part="" 886="" continues="" to="" read="" as="" follows:="" authority:="" secs.="" 501,="" 510,="" 513,="" 515,="" 520,="" 701="" of="" the="" federal="" food,="" drug,="" and="" cosmetic="" act="" (21="" u.s.c.="" 351,="" 360,="" 360c,="" 360e,="" 360j,="" 371).="" 2.="" section="" 886.4392="" is="" amended="" by="" revising="" the="" section="" heading="" and="" paragraph="" (a)="" to="" read="" as="" follows:="" sec.="" 886.4392="" nd:yag="" laser="" for="" posterior="" capsulotomy="" and="" peripheral-="" iridotomy.="" (a)="" identification.="" the="" nd:yag="" laser="" for="" posterior="" capsulotomy="" and="" peripheral="" iridotomy="" consists="" of="" a="" mode-locked="" or="" q-switched="" solid="" state="" nd:yag="" laser="" intended="" for="" disruption="" of="" the="" posterior="" capsule="" or="" the="" iris="" via="" optical="" breakdown.="" the="" nd:yag="" laser="" generates="" short="" pulse,="" low="" energy,="" high="" power,="" coherent="" optical="" radiation.="" when="" the="" laser="" output="" is="" combined="" with="" focusing="" optics,="" the="" high="" irradiance="" at="" the="" target="" causes="" tissue="" disruption="" via="" optical="" breakdown.="" a="" visible="" aiming="" system="" is="" utilized="" to="" target="" the="" invisible="" nd:yag="" laser="" radiation="" on="" or="" in="" close="" proximity="" to="" the="" target="" tissue.="" *="" *="" *="" *="" *="" dated:="" february="" 14,="" 1996.="" d.b.="" burlington,="" director,="" center="" for="" devices="" and="" radiological="" health.="" [fr="" doc.="" 96-5445="" filed="" 3-7-96;="" 8:45="" am]="" billing="" code="" 4160-01-f="">