Reporting live from the 2012 Asia Cornea Society meeting, Manila
Editors' note: This Meeting Reporter contains original reporting by the EyeWorld news team from the 2012 Asia Cornea Society meeting in Manila.
View this video at www.EWrePlay.org/ ACS2012
Donald Tan, M.D., Singapore, president of the Asia Cornea Society and the Cornea Society, summarizes the talks given at the Advanced Keratoplasty Symposium, which kicked off the meeting, sponsored by the Cornea Society.
Nov. 28, 2012
ACS: "Expanding the Realm of the Possible"
The first day of the Asia Cornea
Society's 3rd Biennial Scientific Meeting held in Manila kicked off with a symposium sponsored by the Cornea Society, followed by an opening ceremony in which the ACS bestowed a number of awards, including the Asia Cornea Foundation Medal Lecture and the Asia Cornea Foundation Lecture (Asia).
Penetrating keratoplasty "not dead"
In any discussion of advanced keratoplasty today, that old standard penetrating keratoplasty (PK) remains a valid option. "PK isn't dead yet," said Penny Asbell, M.D., New York. It remains indicated for just about any case and, with current refinements in technique and instrumentation, offers the potential of excellent results with an easier learning curve and without the interface problems of newer modalities.
In fact, it is the preferred option in some cases, such as those that involve full-thickness corneal penetration and advanced keratoconus involving a break in the Descemet's layer.
PK's resilience is in fact aided rather than obviated by new technology: Femtosecond laser-assisted keratoplasty and the option to perform post-PK excimer laser ablation have helped optimize outcomes with the procedure.
future or fad?
Is the use of the femtosecond laser really the future for keratoplasty, or merely a fad? Anthony J. Aldave, M.D., Los Angeles, contemplated the question.
Dr. Aldave enumerated the
advantages of femtosecond laser
keratoplasty, including greater wound strength and wound configuration with better donor-host interface match. Using the laser also means the possibility of earlier suture removal, which has resulted in significantly better measurements of topographic astigmatism at six months. However, this advantage disappears at one year; apparently, he said, suturing technique remains the main determinant for post-op topographic astigmatism.
Still, he said, widespread adoption is limited by the disadvantages: the cost, the risk of intra-op complications including suction loss, and the fact that many patients are not candidates for the procedure owing to anatomic factors.
It therefore remains to be seen whether femtosecond laser keratoplasty is indeed the future, or just a fad.
The thinner the better?
In the evolution of keratoplasty, there has been a rapid transition from PK to endothelial keratoplasty (EK), said Edward J. Holland, M.D., Cincinnati. EK has achieved broader acceptance by having had its early disadvantages of an increased rate of primary donor failure and endothelial cell loss mostly addressed, but current disadvantages include visual outcomes that are still not on par with cataract surgery, and endothelial cell loss remains higher than would be ideal.
In other words, said Dr. Holland, EK is "doing better, but not as well as we would like."
The procedure continues to evolve, and one direction the procedure is headed toward is using thinner tissues.
There used to be a bias toward thicker tissue that was easier to manage, but surgeons have since found that thinner tissue results in better visual acuity. What's more, the
development of donor insertion devices such as the Busin Glide (Moria, Antony, France) and Tan EndoGlide (Angiotech, Vancouver, B.C.) have made thin tissues more manageable.
The next trend, said Dr.
Holland, is Descemet's membrane EK (DMEK), which eliminates stroma from donor tissue to create the thinnest donor tissue possible. However, donor preparation is even more difficult, there is an increase in endothelial cell loss, and there is the risk of rebubbling. In the future, he said, new methods for donor preparation need to be developed, and prospective studies need to compare DMEK with thin EK to establish the true value of the procedure.
Editors' note: Drs. Asbell, Aldave, and Holland delivered their lectures in a symposium sponsored by the Cornea Society. None of the doctors have financial interests related to their lectures.
Standing on the
shoulders of giants
Celebrating the meeting's theme of "Expanding the Realm of the Possible," Richard L. Abbott, M.D., Mill Valley, Calif., delivered a lecture on "Corneal transplantation: The quest for perfection through innovation."
Innovation, said Dr. Abbott, is "to make a change in something established," distinguished from
invention in that it hinges upon a knowledge of prior methods and technology.
Dr. Abbott embarked on a
fascinating review of the history
of ophthalmology, focusing on the groundbreaking work of two giants of modern ophthalmology: Ramon Castroviejo, M.D. (1903-1987), and Max Fine, M.D. (1908-1989).
Dr. Fine, who had been a mentor and sometime colleague of Dr. Abbott, was the first to perform penetrating keratoplasty in the Western United States in 1937, using the technique of square keratoplasty
advocated by his friend and rival, Dr. Castroviejo.
Having dug up old film reels made by Dr. Fine in the 40s and 60s, Dr. Abbott had the films restored and converted to a digital format, which he then presented to the
audience at the opening ceremony of the meeting.
The differences between now and then are fascinating and educational: In his life, Dr. Fine worked barehanded—never once performing surgery wearing surgical gloves,
believing they impaired his performance. And yet he achieved remarkably clear corneas and good outcomes for the time.
Where do you draw the line between using a new technology and what's good for the patient? There is no definite answer, but, said Dr. Abbott, it is the responsibility of surgeons to ask the question. "Our role is to pick and choose [the best option for our patients]," he said. Innovation is clearly a necessity, but the bottom line is whether a particular development is good for the patient.
Editors' note: Dr. Abbott has no financial interests related to his lecture.
Ophthalmologists today have a number of options for managing ocular surface and corneal inflammatory disease, including nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, mast cell stabilizers, combination antihistamine/mast cell stabilizers, immunotherapy, and corticosteroids.
Each agent has its own set of limitations, mostly inherent in their mode of action—antihistamines
reduce itching but not redness,
vasoconstrictors reduce redness but not itching, and corticosteroids bear the stigma of their safety profiles.
This is unfortunate, because, said Edward J. Holland, M.D., Cincinnati, they are the most effective anti-inflammatory agents, offering a broad spectrum of activity that provides the most comprehensive coverage of the inflammatory
cascade of any available agent. These agents suppress the migration of polymorphonuclear leukocytes (PMNs) and the reparative processes and functions of fibroblasts, reverse enhanced capillary permeability, and stabilize lysosomes. Ophthalmologists have come
to fear the elevation of IOP, risk of formation of posterior subcapsular cataracts, aggravation of infectious disease states, and delay in the normal course of healing that has been associated with corticosteroids.
This, said Dr. Holland, has resulted in the suboptimal treatment of active disease and the failure to prevent recurrent disease. The solution may come in the form of the first and, to date, only ester steroid: loteprednol etabonate. Loteprednol, said Dr. Holland, has been shown to be 10 times more lipophilic and have 4.3 times the glucocorticoid receptor binding affinity of dexamethasone—characteristics that significantly alter the safety profile of the drug.
While as effective as the current "gold standard" for steroid therapy—prednisolone—Dr. Holland said that loteprednol has significantly less IOP response, making it ideal for long-term use.
Ophthalmologists, said Dr.
Holland, need to rethink their aversion to corticosteroids, listing dry eye inflammation, meibomian gland disease, chronic conjunctival inflammation, immune stromal keratitis, and even adenoviral ocular infection as indications for corticosteroid use.
Corticosteroids, he said, are the most effective way of avoiding the corneal scarring and pain that are sure to result from undertreating chronic inflammatory eye conditions, complications that are at least commensurate—and also far more likely to occur—than the cataract, glaucoma, and steroid dependence that can be avoided through appropriate and judicious use of available agents.
Engineered against resistance?
In managing keratitis, said John D. Sheppard, M.D., Norfolk, Va., ophthalmologists should consider some important associations: pseudomonas for contact lens ulcers, MRSA/MRSE for at-risk patients, protozoans for unresponsive cases. Basically, he said, it is often best to expect the worst possible bugs when deciding on treatment.
The "worst" includes consideration for growing microbial resistance around the world. There is, said Dr. Sheppard, a growing population of baseline methicillin-ciprofloxacin
resistant bugs. At the rate microbial resistance is rising, it is entirely possible that all bugs are methicillin
resistant within the decade.
Amid these rising resistance rates, Dr. Sheppard touted a new
option for antimicrobial treatment, the first chlorofluoroquinolone:
Bausch + Lomb's formulation of the drug, Besivance (besifloxacin ophthalmic solution 0.6%, Rochester, N.Y.) delivers the drug in a mucoadhesive vehicle of DuraSite, which helps keep the drug on the eye. The molecular characteristics that make besifloxacin what it is—including a chloride in its structure —mean the drug delivers the most balanced inhibition of microbial DNA gyrase and topoisomerase II
action, for a lowered probability
of allowing mutant survivors to
In 696 conjunctival isolates, he said, he has seen no incidence of resistance to besifloxacin.
The drug, he said, offers potent, bactericidal coverage over a broad spectrum of microbes that includes resistant strains.
Safety with contact lenses
Given the ubiquity of contact lens use, the incidence of contact lens-related microbial keratitis—that such infections should occur at all—should be of concern to ophthalmologists.
Fiona Jane Stapleton, Ph.D., Sydney, looked into the various risk factors affecting the incidence of keratitis.
Among the modifiable risk factors Dr. Stapleton examined, she found that using contact lenses six to seven days a week resulted in a six-fold increase in risk; other factors include extended wear, internet purchase, occasional overnight use, poor case hygiene, smoking, daily disposable contact lens use, and
failure to hand wash lenses.
Nonmodifiable risk factors include the initial six-month extended wear of contact lenses, socioeconomic factors, age less than 49 years, hypermetropia, and male gender.
Daily disposable lens use, she said, had the curious effect of increasing the risk of microbial keratitis, but lowering the incidence of severe disease compared with planned replacement daily wear—50% against the 70% seen in patients using the latter.
Dr. Stapleton concluded that incidence has not changed with newer contact lenses, contact lens fluid formulations, and modalities, but that it is possible to limit the severity of the disease by favoring daily disposable lenses and avoiding delay in treatment.
Contact lens and lens case
hygiene being risk factors, Dr.
Stapleton emphasized the need for ophthalmologists to work with industry, regulators, and researchers to establish a standardized set of guidelines for proper product care.
Editors' note: Drs. Holland, Sheppard, and Stapleton spoke at a lunch symposium sponsored by Bausch + Lomb.
Nov. 29, 2012
The Asia Cornea Society's 3rd
Biennial Scientific Meeting continued with sessions that paint closely examined portraits of the cornea, including some surprising architectural details that almost certainly "expand the realm of the possible."
Much has been said about the evolution of corneal transplant surgery, the way the procedure has, over the years, rapidly shifted from one paradigm—the wholesale replacement of the full thickness of the cornea—to another: the deconstruction of the cornea with selective lamellar keratoplasty.
The current paradigm has most recently led to the development of what may be the ultimate iteration of selective lamellar eratoplasty—Descemet's membrane endothelial keratoplasty (DMEK)—but as the procedure is unrefined, at the
moment, cornea surgeons are likely to stay focused on the procedure whose advantages are often touted at cornea meetings: Descemet's
stripping automated endothelial
But while the advantages—less post-op astigmatism, better UCVA, BCVA, and survival than PK, etc.—are well known, Donald Tan, M.D., Singapore, president of the Asia Cornea Society, asked in his plenary lecture: Can these advantages be adopted in Asia? One major impediment to
acceptance, said Prof. Tan, is the
cost of the ALTK microkeratome. As daunting as economic issues typically are in the region, this may not necessarily be insurmountable—the use of precut tissue from a central eye bank, for instance, offers one solution—but there are clinical challenges as well, including: 1. The technically challenging procedure is even more challenging in Asian eyes, which tend to be smaller, with greater vitreous pressure.
2. The main indication for
keratoplasty in the region is pseudophakic bullous keratopathy (PBK); the procedure has been documented to have lower survival and more complications in these cases compared with cases performed for the typical indication in Western countries—Fuchs' dystrophy.
Nonetheless, said Prof. Tan, the procedure is gaining some ground in the region. In Singapore, 77% of keratoplasty cases in 2012 were lamellar. And while it is technically more difficult, their experience further supports the procedure's advantages.
Successful DSAEK, he said, is all about control.
Every step in the development of the procedure, such as in terms of the donor insertion phase—from taco folding to insertion with the EndoGlide (Angiotech, Vancouver, B.C.) that Prof. Tan himself helped develop—has been about improving control.
And yet in order to take the next step, it is often necessary to relinquish the same control that has brought you to the point at which it is possible to take that step. Or something.
DMEK must be among the most extreme forms of selective lamellar keratoplasty ever conceived to date, a procedure in which the tissue to replace is confined to the endothelium, separated from the donor at the Descemet's membrane.
This, said Prof. Tan, means
harvesting and handling tissue that is even thinner and, subsequently, more difficult to control than the thinnest DSAEK.
Regardless, Frank Price, M.D., Indianapolis, thinks that there is unquestionably a role for DMEK in Asia.
Apart from the potential of providing the best possible visual quality of any EK procedure to date, in a very basic sense, DMEK is the next, possibly ultimate, step in the natural progression of EK: By avoiding the creation of an interface, an additional layer where there would not normally be one, DMEK may be the first procedure to truly restore the normal corneal architecture.
While techniques for donor preparation and insertion as well as post-op management can be improved, the results Dr. Price currently achieves with the procedure are far superior to the results of any form of DSAEK. Sites from around the world that frequently prepare donor tissue for DMEK have donor tissue loss rates less than 1%—at least as good as donor tissue loss rates for ultrathin DSAEK. The cell loss rates Dr. Price has seen with DMEK are comparable to cell loss rates at other sites in the U.S. performing DSAEK. In addition, in some cases, it is possible that
reported rates of cell loss were exaggerated by the method used for counting cells by eye banks.
Dr. Price believes that DMEK will continue to be the best option for most of the U.S. and Asia until viable methods for simply injecting endothelial cells or stimulating the regeneration of the patients' own endothelial cells are developed.
Editors' note: Prof. Tan helped develop the Tan EndoGlide, but has no financial interests in the device. Dr. Price has no financial interests related to his comments.
Redefining corneal architecture
The big bubble technique has always been presumed to cleave the cornea at the Descemet's membrane. But this might not always be the case. After a series of observations involving the procedure, Harminder S. Dua, M.D., Nottingham, U.K., began to suspect the existence of a distinct layer in the posterior stroma that is different from the Descemet's membrane.
Prof. Dua devised a simple test for his hypothesis: He performed the big bubble technique on four whole globes and 21 sclero-corneal discs. The paper, in press, was the subject of his plenary lecture at the meeting.
He found that performing the technique results in one of three types of bubbles: Type 1 emerges centrally, forming a well-circumscribed central dome 7-8.5 mm in diameter. Type 2 is thin-walled,
begins peripherally, resulting in a bubble with a much larger diameter. Type 3 mixes the characteristics of the two.
With a type 1 bubble, the
Descemet's membrane can be peeled off entirely, histologically intact, without bursting the bubble. Peeling a type 2 bubble, on the other hand, immediately deflates it; what's more, after peeling, the surgeon can create a type 1 bubble in the remaining tissue.
Through subsequent histologic examination, Prof. Dua identified five to eight compact lamellae of type 1 collagen immediately anterior to the Descemet's membrane, posterior to the last row of keratocytes.
This pre-Descemetic "Dua's Layer" has several implications, including: a DL-DMEK is likely to be easier to handle and unfold than DMEK; the layer may have a role to play in acute hydrops of keratoconus and in pre-Descemet's dystrophy; it may influence corneal curvature and biomechanics.
Editors' note: Prof. Dua has no financial interests related to his lecture.
Keratoconus in the dark
While much work, even progress, has been made in the diagnosis and management of keratoconus, the pathogenesis of the condition remains poorly understood, said Gerard Sutton, M.D., Sydney.
The histopathologic pattern is clear: central, paracentral thinning with breaks in Bowman's capsule and decreased keratocyte density, but is this the result of defective
formation or tissue loss or a combination of the two? Epidemiology provides some clues—the condition is very common in India, suggesting a genetic basis—while also seeming to contradict them—this prevalence is not seen among Indians living in the U.K., suggesting environmental
Although genes and systemic conditions have been associated with keratoconus, the data, said Dr. Sutton, suggests sporadic or incomplete penetrance.
Keratoconus appears to be the end stage of multiple disease entities with different pathogenesis, resulting from a cascade that begins with a genetic predisposition, followed by an environmental factor or some other indeterminate "second hit," leading to epithelial cell abnormalities that in turn cause alterations in signaling stimulating apoptosis.
This suggests the potential for a single pathway on which it may be possible to target therapy: the "wnt" pathway.
Fortunately, despite the obscurity of its pathogenesis, there is a wide range of options for managing the condition. Penny Asbell, M.D., New York, described some useful tools surgeons may not be aware of, or might not utilize enough if they do: contact lenses.
Dr. Asbell described three new kinds of contact lens designed for keratoconus: hybrid lenses combining a rigid gas-permeable lens with a soft skirt; soft contact lenses specially designed to vault over the keratoconus; and scleral contact lenses, also designed to vault over the cornea.
Patients need to be trained to use these lenses properly, but they are valuable tools for keratoconus patients in whom surgery may not be the immediate preferred option.
Editors' note: Drs. Asbell and Sutton spoke at a symposium on keratoconus sponsored by the American Academy of Ophthalmology. They have no financial interests related to their lectures.