FDA ADVERSE EVENTS
Adverse Events by Lens Type
what 12 years of data tells us about hydrogels, silicone hydrogels, GPs and decorative
By Brian Chou, OD, FAAO
FDA receives information about medical device adverse events including those
involving contact lenses from manufacturers, importers and user facilities
through its Medical Device Reporting (MDR) program. The FDA uses these reports to
detect medical device problems and to intervene if necessary. Since 1984, the FDA has
required manufacturers and importers of medical devices to report all device-related
deaths, serious injuries and certain malfunctions.
Despite this requirement, the FDA received
only a handful of adverse event reports. A 1986 General Accounting Office study
showed that less than 1 percent of device problems occurring in hospitals were reported
to the FDA, and the more serious the problem with a device, the less likely it was
to be reported.
address this shortcoming, the Safe Medical Devices Act (SMDA) of 1990 required device
"user facilities" to also report device-related adverse events to the FDA. The
Medical Device Amendments of 1992 clarified certain terms and established a single
reporting standard for device user facilities, manufacturers, importers and distributors.
It's not fully known to what extent these actions have improved mandatory adverse-event
The cumulative MDR data is organized
under the Device Experience Network (DEN) and the Manufacturer User Facility and
Distributor Experience (MAUDE) databases. The DEN database includes reports received
under the mandatory MDR program from 1984 to 1996 and voluntary reports from patients
and practitioners up to June 1993. The more recent MAUDE database includes mandatory
manufacturer reports since August 1996 and voluntary reports from patients and practitioners
since June 1993. A user can search each online database for information on medical
devices that may have malfunctioned, caused serious injury or even caused death.
of Reported Adverse Events from 1994 to 2005
diagnosed or presumed by practitioner or manufacturer
Non-severe adverse event
including these subcategories:
Abrasion, some due to faulty lenses
Inflammation, infection other than MK
� Uveitis 12
Toxicity reaction from care regimen,
packaging solution or unknown 9
� Neovascularization, edema or corneal
Contact lens papillary conjunctivitis
Cutting fingers on package foil
Lens damage, either torn
or defective lens
including pain, irritation, eye injury � unlikely MK
Sold by unregistered
Note: Figures in parentheses were reportedly sold by an unregistered
vendor and were categorized accordingly under MK, non-severe adverse event or
uncertain diagnosis. There were also three reports of contact lenses sold by an
unregistered vendor but without any specified adverse event.
About MAUDE Data
The MAUDE database may reflect recent trends of
adverse events by contact lens type. To avoid any misunderstanding, be advised that
the medical device reporting system isn't a controlled process, meaning that several
sources of confounding variables exist that prevent scientific conclusions. In fact,
the FDA states that the MAUDE data is not intended for evaluating rates of adverse
events or for comparing adverse event occurrence rates across devices. Consistent
with this caveat, I did not calculate incidence rates of adverse events, despite
temptation to use available market share data for each contact lens type to do exactly
that. Similarly, it wasn't possible to perform statistical analyses to determine
whether changes in reporting for particular lens types resulted from chance variation
or were statistically significant.
Instead, I retrieved 12 years worth of contact
lens-related adverse event reports from the FDA Web site. I categorized the contact-lens
related adverse events for each year according to lens type (hydrogel, silicone
hydrogel, gas permeable and decorative lenses), the type of adverse event and who
reported the incident.
This article summarizes trends in adverse
events reporting to the FDA by lens type while relating the findings to possible
changes in the contact lens industry and prescribing habits over the same period.
What Constitutes a Reportable Event?
The FDA encourages voluntary adverse event reporting
by consumers and practitioners using Form 3500 available online. According to the
FDA, Form 3500 "should be used by healthcare professionals and consumers for voluntary
reporting of serious adverse events, potential and actual product use errors, and
product quality problems associated with the use of FDA-regulated drugs, biologics
(including human cells, tissues, and cellular and tissue-based products), medical
devices (including in vitro diagnostics), special nutritional products and cosmetics."
There is certainly leeway for interpreting
what constitutes an adverse event. For example, the FDA asks consumers to submit
a report "If you think you or someone in your family has experienced a serious reaction
to a medical product..." Practitioners are told that "An adverse event is any undesirable
experience associated with the use of a medical product in a patient." Furthermore,
the FDA advises practitioners that the event is "serious" when the patient outcome
is death, life-threatening, requires hospitalization, involves disability, causes
congenital anomaly or requires intervention to prevent permanent impairment or damage.
In contrast to voluntary reporting,
medical device manufacturers are required to report all "MDR reportable events"
to the FDA on Form 3500A, also available online. A report is required when a manufacturer
becomes aware of information that reasonably suggests that one of its marketed devices
has or may have caused or contributed to a death or serious injury, or that it has
malfunctioned and that the device or a similar device marketed by the manufacturer
would likely cause or contribute to a death or serious injury if the malfunction
were to recur.
Contact Lens-related Adverse Events
1. Number of reported MK cases by year and lens type.
The contact-lens related adverse events I evaluated
from the MAUDE database included microbial keratitis (MK), corneal abrasion, unspecified
ocular irritation and lens defects such as split lenses and incorrect packaging
About 60 percent (360/584) of the reports
were attributed to MK or presumed MK during the 12-year period (Figure 1). MK was
the most common reason for an adverse event report. Starting in 1996, an average
of 26 reports occurred per year over the next seven years, with hydrogel lenses
(defined for the purposes of this article as all hydrogel lens types except for
silicone hydrogels and decorative hydrogel lenses) as the predominant lens type.
Since 2003, the number of reports attributed to MK increased to more than 50 reports
Nearly 20 percent (114/584) of events
were classified as non-severe and included conditions such as corneal neovascularization,
papillary conjunctivitis, allergic or toxic response and corneal abrasions. The
non-severe events unrelated to contact lenses included idiopathic iritis and four
events in which patients cut fingers while handling lens packaging. About 8 percent
(49/584) were classified as uncertain diagnoses that were unlikely to be MK. These
cases described signs and symptoms but gave no diagnosis, or insufficient information
was available to categorize the reported event. About half of the cases of uncertain
diagnosis came from a voluntary report on the FDA database, while about one-fifth
followed a letter from a patient's attorney to the manufacturer. About 10 percent
(58/584) of reports were due to defective lenses, with eight of the 10 categorized
as voluntary reporting, many by patients. Reports of defective lenses were fairly
consistent in number over the 12-year period, averaging four to five reports per
year with the majority (82 percent) associated with hydrogel lenses.
An Increasing Number of Reported Incidents
Between January 1994 and December 2005, a total
of 584 contact lens-related adverse events were categorized in the MAUDE database.
The annual number of contact lens-related adverse event reports increased from 19
in 1994, when the system was started, to a high of 102 reports in 2003, when approximately
one-quarter of the reports involved silicone hydrogels. Since 2003, there has been
a slight decline in the number of reports, with 84 in 2005.
The relatively low number of reports in 1994
and 1995 during the inception of the MAUDE database represented voluntary reporting
from individual patients or practitioners, often with limited information. Approximately
one-third of these early reports were classified as having an uncertain diagnosis
because of a lack of information. Since 1996, when manufacturers began recording
adverse events in the MAUDE database, the number of reports has steadily risen along
with an increased level of detail about each event. The higher volume of reports
may also reflect increased patient and practitioner familiarity with the FDA database.
Nevertheless, the total of 584 clearly represents a significant under-reporting
of all actual cases of adverse contact lens events.
Figure 2 summarizes the results over
the 12 years according to lens type. The events were associated with a range of
lens types, with hydrogels (403/584) taking the majority, followed by silicone hydrogels
(89/584), decorative hydrogels (58/584) and GPs (15/584). Three percent (19/584)
of reported incidents involved unknown or miscellaneous lenses, such as Softperm
Figure 2. Reported events
by year and lens type.
Sources of Reporting
There were no manufacturer-reported events for
1994 or 1995 because the MAUDE database did not tabulate such events until August
1996. Instead, practitioners or patients voluntarily reported the 27 total events
in 1994 and 1995. Excluding the MAUDE data from 1994 and 1995, approximately 75
percent (417/557) of the contact lens-related adverse event reports originated through
manufacturers (Figure 3) during the time from 1996 to 2005. About 5 percent (29/557)
of reports followed communication from a patient's attorney, either directly to
the FDA or via the manufacturer or practitioner. Less than 1 percent (5/557) of
events came from manufacturers after a case report in a peer-reviewed journal showed
that their lens was involved with a significant adverse event. With one-fifth of
reports since 1996 reported on a voluntary basis, practitioner or patient bias may
have resulted in an under- or over-reporting of events for certain lens types.
Manufacturer reporting of clinical study-related
incidents has increased with 15 cases reported since 2000; four of them involving
hydrogels and the remaining 11 involving silicone hydrogels. It's possible that
other clinical study-related incidents occurred during this same period, but may
have escaped identification as coming from a clinical study in the FDA reporting.
It's important to know that the adverse
incidents from the MAUDE database are not reports exclusively from the United States.
Patients and practitioners worldwide can access the database. Indeed, some manufacturer-generated
reports came from a foreign affiliate to a U.S.-based manufacturer that then reported
the event. Unfortunately, not enough information is available in the MAUDE data
to know how many of the reports originated outside of the United States. Therefore,
the trends among the reported incidents may be influenced to some degree by the
prescribing in other countries, which we should take into consideration when comparing
them to U.S. prescribing trends. It's known that the pattern of contact lens prescribing
outside of the United States differs by lens type and modality.
The predominant lens type associated with
adverse events reported to the FDA has been hydrogels. The number of reported MK
events by lens type shows that the occurrence with hydrogels has been fairly static
over the last 10 years, averaging 24 reports a year. In 1996, all reports were with
hydrogel lenses. However, the proportion of reports related to hydrogels has decreased
in recent years, probably because of increased prescribing and manufacturer clinical
study of silicone hydrogels. In 2005, hydrogels accounted for 60 percent of reports.
3. Who reported the events (1996-2005)
Reported events with silicone hydrogel lenses
have increased between 2001 and 2005, with the number of MK reports reasonably similar
between silicone hydrogels and hydrogels, except for 2004. Reported MK events with
silicone hydrogels have increased over the last four years, with an average of 16
per year. In 2005, there were 21 reports of MK with silicone hydrogels compared
to 29 with hydrogels. This increase may have resulted from the growing popularity
of silicone hydrogel prescribing and their close monitoring by manufacturers. It's
unknown how many MK reports were attributable to daily or extended wear, although
industry data shows that practitioners currently prescribe silicone hydrogels more
for daily wear. Furthermore, it wasn't always clear how the lenses were worn or
prescribed. For example, several reported adverse events involved patients who noncompliantly
wore a silicone hydrogel indicated for daily wear overnight.
first silicone hydrogel lens appeared in 1999 for six-night extended wear, and in
2001 two silicone hydrogels obtained approval for 30-day continuous wear. In the
first few years that silicone hydrogel lenses were commercially available, the majority
were prescribed for extended wear. The increase in adverse event reporting involving
silicone hydrogel lenses results partly from more of the lenses being prescribed,
which increased from approximately 1 percent of soft spherical lenses in 2001 to
5 percent in 2003.
After 2003, although the number
of reported incidents remained fairly static for silicone hydrogels, the number
of these lenses prescribed increased significantly. Among soft spherical lenses,
silicone hydrogel lenses accounted for about 18 percent in 2004 and nearly one-third
in 2005. During this time, practitioners increasingly prescribed silicone hydrogels
for daily wear, with some of the lenses specifically marketed for daily wear. In
2005, approximately two-thirds of silicone hydrogels prescribed had a specific daily
wear indication. However, this shift toward daily wear wasn't associated with a
decrease in reported events with silicone hydrogels, as we might expect.
You might think that six years
following the launch of silicone hydrogels, their increasing use might be associated
with fewer reported adverse events compared to hydrogels. However, evaluation of
the MAUDE data doesn't support such a hypothesis. A recent study in Australia showed
no significant difference in MK incidence with the overnight wear of silicone hydrogels
and hydrogels. Other studies have concluded that while overnight wear increases
MK incidence, silicone hydrogel overnight wear is associated with less risk than
hydrogel overnight wear. Even with more evidence emerging about contact lens safety,
it remains unknown whether silicone hydrogels provide greater safety for overnight
wear than do hydrogels. This realization should stimulate practitioners to critically
assess silicone hydrogel clinical performance for daily wear and extended wear.
While the MAUDE data shows a relatively
high number of silicone hydrogel events, it's not possible to determine whether
this is abnormal. For example, this finding may result from practitioners prescribing
a disproportionate number of silicone hydrogels for problematic or "at-risk" patients.
It's also possible that the newness and interest in silicone hydrogels compared
to other lens technologies is leading to an over-represented number of reports.
Finally, this data may represent extensive clinical study and monitoring of silicone
hydrogels by manufacturers compared to other lens types.
Gas Permeable Contact Lenses
As some of you might expect, the number of adverse
event reports with GP lenses was low over the 12 years. However, a small increase
in reported events occurred in 2004 and 2005; all were cases of MK with overnight
wear of high-Dk/t orthokeratology lenses. This appears related to increased practitioner
prescribing of overnight corneal reshaping GPs in recent years following the FDA
approval of Corneal Refractive Therapy (Paragon Vision Sciences) in 2002; Contex
OK-E (Contex) and Emerald (Euclid Systems) in 2004; and Vision Shaping Treatment
(Bausch & Lomb) in 2005. Despite evidence for the clinical efficacy of ortho-k
for the temporary reduction of myopia, there are increasing reports of MK with ortho-k.
Non-compliance and use of tap water are common risk factors. Although there still
is no known incidence for MK with overnight ortho-k, several studies have identified
that overnight ortho-k is an important risk factor for MK, especially for children.
The steady but low number of adverse events for
decorative lenses changed between 2002 and 2004, with a substantial increase in
reporting and an average of 12 annual cases in 2003 and 2004. The number of reports
compared to their relatively low use might be concerning, although a reduction to
just five events followed in 2005. It wasn't possible to differentiate whether the
decorative lenses were plano or for correcting refractive error, but approximately
one-quarter were allegedly supplied without a prescription by non-licensed vendors.
This may have caused the increase in reporting a few years ago, as practitioners
may have wanted to demonstrate to the FDA the existence of adverse events including
MK with decorative lenses. Unlicensed vendors sold some of these decorative lenses
without confirming that the patients had an ocular assessment, customized fitting
or verbal counseling regarding lens care, and they offered no provision for aftercare.
With several published cases of vision loss related to the improper wear and care
of decorative contact lenses, legislators now seem to understand that the potential
complications exist whether or not the contact lenses correct for refractive error.
Publicity generated in the professional and lay press during this time about the
risks associated with wearing plano, decorative lenses without a prescription helped
to effect legislative changes, culminated by the passage of a bill in November 2005
to protect patients from eye injuries resulting from inappropriately filled prescriptions
for decorative lenses. The reduction in 2005 of reports with decorative lenses may
have resulted from the new legislation to protect patients. It's possible that practitioners
are satisfied knowing that plano decorative lenses are regulated like all other
contact lenses, such that they don't have as much incentive to point out decorative
contact lens complications to the FDA.
Although it's unknown how accurately this summary
reflects true clinical experience with various contact lenses, it does offer perspective
on changes that have taken place in the contact lens industry. For example, the
increased reporting of adverse events with decorative lenses in 2003 and 2004 seems
related with decorative lens legislation introduced during that time. Additionally,
the notable increase in adverse event reporting involving silicone hydrogel lenses
follows the dramatic trend of practitioners prescribing these lenses in greater
numbers. As a final illustration, the upward trend of events with GPs coincides
with increased prescribing of overnight corneal reshaping.
Yet it's difficult to ascertain the diagnoses
and lens types reported to the FDA, along with other relevant information such as
patient compliance and whether patients wore the lenses on a daily or extended wear
basis. With these limitations in mind, monitoring the FDA data may offer an alternative
tool for examining contact lens industry trends to supplement the more traditional
estimated sales volume and practitioner surveys.
Dr. Chou acknowledges Visioncare
Research Ltd. for its expertise in the data compilation and Mark Bullimore, MCOptom,
PhD, FAAO, at The Ohio State University College of Optometry, and his vision science
students for reviewing this article.
To obtain references for this
article, please visit
http://www.clspectrum.com/references.asp and click on document
Dr. Chou is in group practice in San Diego
at Carmel Mountain Vision Care. He is also the co-developer of
EyeDock.com, an online
contact lens reference for doctors.
Contact Lens Spectrum, Issue: December 2006