Was the year 2000 among the good old days? It is difficult for me to remember, especially when it comes to my practice. I had been out of fellowship for 7 years, and my practice had become extremely busy. For me, it seems useful to discuss several areas of practice: the office and medical care of patients, research, and the surgical care of patients.
MEDICAL THERAPY
We physicians had several new medications to use. After
4 years' experience with the drug, we were using latanoprost
(Xalatan; Pfizer Inc.) as first-line therapy. Unoprostone
(Rescula; Novartis Ophthalmics, Inc.), another
prostaglandin analogue, was introduced that year, and
many of us were gaining clinical experience with it. The
fixed combination of dorzolamide and timolol (Cosopt;
Merck & Co., Inc.) was in wide use, and there was a great
deal of buzz concerning brimonidine (Alphagan; Allergan,
Inc.) and the possibility of neuroprotection. Animal studies
in this area seemed to be quite promising.
The introduction of each new medication brought short-term reductions in glaucoma surgery, as we hoped these agents would preclude the need for surgery. Many of us were also trying to find a niche for all of the &bets;-blocker drops. Alas, medical therapy usually just delayed surgery.
RESEARCH
The seventh report from the Advanced Glaucoma
Intervention Study (AGIS)1 provided strong evidence
that low pressures were useful in preserving vision in
advanced glaucoma. Many of us who were already
adopting lower target pressures for more severe glaucoma
now felt justified in lowering them even further.
SURGERY
The availability of small, portable diode lasers at 810 nm
made it easier for those of us with satellite offices to provide provide
laser trabeculoplasty at each location. These units
were also useful for suture lysis after trabeculectomy. The
Nd:YAG laser for selective laser trabeculoplasty had been
recently introduced and was showing promise, although it
was not yet available in the United States.
Surgically, 2000 was an interesting time for me, especially in regard to nonpenetrating glaucoma procedures. Many of us, myself included, were tired of managing the bleb-related complications of trabeculectomy, and the promise of surgeries that did not depend on a bleb and perhaps had fewer complications was extremely attractive. I had been performing viscocanalostomy for about 2 years and was often a little disappointed with the intermediate-term results. I found a good deal of anecdotal evidence from European researchers like Philippe Sourdille, MD, and André Mermoud, MD—which was later backed by studies—that combining a spacer device such as the AquaFlow Collagen Drainage Device (STAAR Surgical Company, Monrovia, CA) with mitomycin C (MMC) could greatly improve the long-term success of nonpenetrating deep sclerectomy.
These were not blebless surgeries, but usually the bleb was posterior, low lying, and thicker than those of trabeculectomy with MMC. Complication rates (both short- and long-term) seemed lower, with fewer cases of hypotony-related complications like choroidal effusions and flat chambers as well as fewer bleb leaks. The procedure was somewhat more technically demanding than trabeculectomy,2 especially in terms of the creation of a trabeculo-Descemet's window and peeling the deep layer of Schlemm's canal.
In addition, nonpenetrating deep sclerectomy had a few unique complications, including fibrosis of the trabeculo- Descemet's window with a loss of permeability and increased IOP. The remedy was also unique: the use of Nd:YAG goniopuncture. Another complication not usual in trabeculectomy was incarceration of the iris in the trabeculo-Descemet's window, since a peripheral iridotomy was not routine. This problem could sometimes be solved with laser gonioplasty, iridoplasty, and iridotomy. Other cases required a trip to the OR to reduce the incarceration and perform a surgical iridotomy. Fortunately, I achieved long-term success with this procedure, and many of these eyes still have functioning blebs.
CONCLUSION
In the subsequent decade, more prostaglandin analogues
have come on the market, and we clinicians have
moved away from and back to ß-blockers, other fixedcombination
agents, and a plethora of generics. My office
staff is now constantly hounded by managed care plans
to persuade me to change my patients' medications.
Neuroprotection in humans remains elusive. In my practice,
selective laser trabeculoplasty has supplanted argon
and diode laser trabeculoplasty. Canaloplasty with suture
tensioning has replaced deep sclerectomy as my nonpenetrating
surgery of choice, again with the promise of
a blebless procedure. Many of us are striving for a better
surgical alternative for lowering IOP.
The good old days were not in 2000 for me, but in many ways, this year was evolutionary with regard to the practice of glaucoma.
This article article discusses off-label uses of medications.
Richard A. Lehrer, MD, is the director of Glaucoma Services at Ohio Eye Alliance in Alliance, Ohio, and an assistant clinical professor of ophthalmology at Northeast Ohio Universities College of Medicine in Rootstown. He is a consultant to Alcon Laboratories, Inc., and iScience Interventional. Dr. Lehrer may be reached at (330) 823- 1680; rlehrer@ohioeye.com.
BY LISA F. ROSENBERG, MD
As the 21st century began, physicians availed
themselves of a wide variety of diagnostic
tests and a growing arsenal of topical glaucoma
therapies.
DIAGNOSTICS
With the millennium came a new paradigm in the characterization
of the optic nerve. Although stereo disc photography
remained the gold standard, automated optic
nerve analyzers became widely used in clinical practice.
With the aim of earlier detection of glaucomatous optic neuropathy, three techniques emerged: scanning laser
polarimetry (GDx; Carl Zeiss Meditec, Inc., Dublin, CA),
confocal scanning laser ophthalmoscopy (Heidelberg
Retina Tomograph; Heidelberg Engineering GmbH,
Heidelberg, Germany), and optical coherence tomography
(Stratus OCT; Carl Zeiss Meditec, Inc.). The ability to
accurately, objectively, and quantitatively measure the
optic nerve was innovative and extraordinarily appealing.
Patients and ophthalmologists alike were intrigued by this
concept, which wowed both groups with snazzy, threedimensional,
color images created in a few seconds. These
devices held the promise of becoming an essential and
complementary element of glaucoma care, even if their
long-term role was yet to be established.
Two visual field strategies became available for clinical use. By testing a sparse and less redundant system of ganglion cells with blue light on a yellow background, shortwavelength automated perimetry allowed ophthalmologists to demonstrate early functional loss sooner than standard white-on-white perimetry. This method of testing proved powerful in high-risk patients with clear media. Frequencydoubling perimetry presented a frequency-doubled illusion at a low spatial frequency sinusoidal grating thought to measure the function of a subset of ganglion cells different from those assessed with short-wavelength automated perimetry. Because of its high correlation with glaucomatous defects measured by standard perimetry, the utility of frequency-doubling perimetry lay in its short testing time and its ease of use for screening. Glaucoma specialists now had more than one strategy by which to characterize functional ocular deficits.
PHARMACEUTICALS
The popularity of miotics and oral carbonic anhydrase
inhibitors was falling, as myriad new and effective topical
therapies became available. Most notably, latanoprost
(Xalatan; Pfizer Inc.), which had been approved for use in
1996, was joined by bimatoprost (Lumigan; Allergan, Inc.)
and travoprost (Travatan; Alcon Laboratories, Inc.). This
class of drugs was not only extremely effective at lowering
IOP, but it also offered a practical dosing schedule for
patients who had a track record of poor adherence to
prescribed therapy.
Nevertheless,10 years ago, timolol was still the first-line drug of choice, and prostaglandins were relegated to third- or fourth-line therapy. Concerns over iris pigmentation and ocular redness deterred some patients from using prostaglandin analogues. These agents demanded extra “chair time” from ophthalmologists in order to explain their side effects and field patients' phone calls about red, irritated eyes.
Other new therapeutic options at the time included the first fixed combination of dorzolamide and timolol (Cosopt; Merck & Co., Inc.) and a new formulation of the α-adrenergic brimonidine-Purite 0.15% (Alphagan; Allergan, Inc.) designed to reduce ocular allergy. Generic medications were becoming available. Their efficacy was questioned by some clinicians, however, and these agents did not gain a significant market share.
The holy grail of neuroprotection became a big topic at clinical meetings. Evidence that neuroprotection might play a role in glaucoma therapy could be found in cell culture and animal models of optic nerve injury and ischemia, which demonstrated that the death of retinal ganglion cells could be prevented by specific pharmacologic agents.1 Toward this end, the multicenter, randomized, clinical investigation of memantine was initiated. A multicenter, prospective, randomized trial was already underway to determine if brimonidine 0.2% had a neuroprotective effect independent of IOP in patients with normal-tension glaucoma.
TREATMENT ALGORITHM
With so many possible therapeutic combinations, the
definition of maximal medical therapy was debated at
meetings. The selective laser was not yet an option for
trabeculoplasty, so argon laser trabeculoplasty was
kicked down the treatment algorithm after medical
management failed to adequately control IOP. As a
result, less laser and incisional surgery was being performed
nationwide.
Trabeculectomy, with or without antifibrotic therapy and releasable sutures, and seton surgery were established modes of surgical treatment at the turn of the millennium. In response to the continuing search for a surgical procedure with improved efficacy and reduced complications, the concept of nonpenetrating surgery was introduced in the form of viscocanalostomy. It was embraced by comparatively few ophthalmologists. Most glaucoma surgeons remained a conservative bunch and greeted this technique with skepticism.
CONCLUSION
Overarching challenges in glaucoma remain lightening
rods for research and clinical care regardless of the decade. Where does the site of outflow resistance reside
in glaucoma? What damages the optic nerve? What is the
best initial surgery for glaucoma? How is functional progression
best detected? How is structural change best
detected? Clinicians are fortunate to work in a dynamic
field where the management of and cure for glaucoma
are lofty and challenging pursuits but ones that are thoroughly
fulfilling.
Lisa F. Rosenberg, MD, is an associate professor of clinical ophthalmology at the Feinberg School of Medicine, Northwestern University, in Chicago. She acknowledged no financial interest in the products or companies mentioned herein. Dr. Rosenberg may be reached at (312) 475-1000; lisarosenberg731@yahoo.com.
BY WILLIAM ERIC SPONSEL, MD
What a year 2001 was! We physicians were
definitely a part of the big new wave; we
were not necessarily riding its very crest,
but we were not watching from the shoreline,
either. I think it fair to say that those of us involved
in clinical practice were bravely bodysurfing the myriad
Y2K tidal changes. The fact that clinical practice a decade
ago was in many ways similar to how it is today is more a
reflection of the rapid changes that immediately preceded
the year 2000 than undue stagnancy since.
DIAGNOSTIC TECHNOLOGY
Major epidemiologic studies revealed the stunning
reality that normal-tension glaucoma comprised the
major proportion of all open-angle glaucoma sufferers
worldwide.1-6 On cue, the new millennium brought us
the necessary means to diagnose glaucoma in everyone,
regardless of the presence or absence of ocular hypertension.
The ingenious innovation of Ted Madess, PhD, the
frequency-doubling perimeter was commercially developed
by Welch Allyn Medical Products (Skaneateles Falls,
NY) and wisely acquired by Carl Zeiss Meditec, Inc.
(Dublin, CA). The frequency-doubling perimeter provided
previously unheard of levels of diagnostic sensitivity
and specificity. The device was promptly officially recognized
by Prevent Blindness America's Glaucoma Committee
and adopted by the Congressional Glaucoma Caucus,
which initiated a new era in glaucoma screening.
Early glaucoma detection and structural monitoring took off in 2000 as well, as reflected in an influential article7 by Linda Zangwill, PhD, and colleagues that compared the HRT (Heidelberg Engineering GmbH, Heidelberg, Germany), GDx (Carl Zeiss Meditec, Inc.), and optical coherence tomographer (Carl Zeiss Meditec, Inc.). These technologies were newly in clinical use by then, and nerve fiber layer imaging has become a mainstay of modern clinical practice.
SURGERY
All of the current forms of laser therapy were widely
used except for selective laser trabeculoplasty. Mitomycin
C was supplanting 5-fluorouracil as the favored
antifibrotic agent, and the nonpenetrating procedures
introduced by Thom Zimmerman, MD, PhD, and popularized
by André Mermoud, MD, were gaining worldwide
acceptance. The pioneers of viscocanalostomy were
already hard at work, and almost all subspecialists had
replaced top hat scleral tunnel combined procedures
with clear corneal phacoemulsification and separate-site
filters.
Tube shunts had evolved into high-quality implants very similar to those currently available. Tutoplast (IOP Inc., Costa Mesa, CA) and eye-banked sclera were both acceptable options for reinforcement grafts.
MEDICAL THERAPY
Our available drug list was much as it is now, with the
β-antagonists timolol, betaxolol, carteolol, and levobunolol
in common use alongside the α-agonists dipivefrin,
apraclonidine, and newcomer brimonidine. The
topical carbonic anhydrase inhibitors dorzolamide and
brinzolamide had also been recently introduced. As the
1990s drew to a close, the number of prostanoids—the
most effective class of topical ocular antihypertensive
agents ever developed—expanded dramatically. Unoprostone,
bimatoprost, and travoprost entered the market
in rapid succession. This class of medication was such
an impressive addition to our pharmacologic armamentarium
that it actually put a significant crimp on the
number of filtering procedures performed, even as the
baby boomers began to swell the glaucoma population.
Mechanistically unique, prostanoids increased aqueous
outflow without regard to episcleral venous pressure. This difference opened up the possibility of treating a
huge new cadre of patients, including those with normotensive
open-angle glaucoma. The approval of the
first combination agent, Cosopt (timolol and dorzolamide;
Merck & Co., Inc.), provided us with another eye
drop that had potency commensurate with and additive
to that of the prostanoids.
Still, we wanted more. Clinical and laboratory studies had made us aware of the potentially positive vasoactive effects of the carbonic anhydrase inhibitors and neuroprotective benefits of the α-agonists and ß-blockers (betaxolol in particular). We naturally had high hopes of new vasoactive and neuroprotective agents that would help us contend with all the nonhydrostatic predisposing factors for open-angle glaucoma. No glaucoma drug had (or has) ever attained FDA approval by demonstrating a benefit in terms of visual function or neural structure. Who would have believed then that we would still be waiting?
CONCLUSION
Here is to the strong and brave new glaucoma generation!
May they have the will to grab their boards and
ride high above the aqueous surf to give future generations
effective new therapeutic agents that modulate
the full spectrum of factors underlying chronic glaucoma.
In so doing, may these physicians and researchers
lead the way toward better treatments for Alzheimer
disease, Parkinson disease, and other debilitating neuropathies!
Cowabunga!
William Eric Sponsel, MD, runs a busy referral practice in San Antonio that specializes in the treatment of complex glaucoma, hypotony, and eye trauma. Dr. Sponsel is also actively involved with efforts to mitigate the devastating effects of ocular trauma among the US armed forces abroad. He acknowledged no financial interest in the products or companies mentioned herein. Dr. Sponsel may be reached at (210) 223-9292; sponsel@earthlink.net.
