EyeWorld Asia-Pacific
The News Magazine of the Asia-Pacific Association of Cataract & Refractive Surgeons (APACRS)

MEETING REPORTVolume 8 Number 4

ACS 2012: ‘Expanding the Realm of the Possible’

by Chiles Aedam R. Samaniego EyeWorld Asia-Pacifi c Senior Staff Writer

Reporting live from the Asia Cornea Society’s 3rd Biennial Scientifi c Meeting, 28-29 November 2012

MANILA, DAY 1—The fi rst day of the Asia Cornea Society’s 3rd Biennial Scientific Meeting held here 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).

Femto keratoplasty—future or fad?

But is the use of the femtosecond laser really the future for keratoplasty, or merely a fad? Anthony J. Aldave, MD, Los Angeles, Calif., USA, contemplated the question.

Dr. Aldave enumerated the advantages of femtosecond laser keratoplasty, including greater wound strength and wound confi guration with better donorhost interface match.

Using the laser also means the possibility of earlier suture removal, which has resulted in signifi cantly better measurements of topographic astigmatism at 6 months. However, this advantage disappears at 1 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, MD, Cincinnati, Ohio, USA. 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 and Tan EndoGlide (Angiotech, Vancouver, BC) 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 diffi cult, 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. Aldave and Holland delivered their lectures in a symposium sponsored by the Cornea Society. They have no fi nancial interests related to their lectures.

‘Expanding the Realm of the Possible’

“The pursuit of education in the cornea subspecialty remains a most important mission of the Society,” said Donald Tan, MD, Singapore, president of the Asia Cornea Society. To this end, the organizing committee has put together a “stimulating scientifi c program delivered by over 70 eminent international and regional corneal opinion leaders” around the theme of “Expanding the Realm of the Possible.”

At the opening ceremony of this year’s meeting, the 3rd Biennial Scientifi c Meeting of the Society, the ACS presented a number of awards: The Asia Cornea Foundation Medal, a medal lecture and the Society’s most prestigious award “presented to a corneal specialist in recognition of an outstanding lifetime contribution to the fi eld of cornea” was given to Richard Abbott, MD, Mill Valley, Calif., USA. The Association of Eye Banks of Asia (AEBA) Award, presented to “an ophthalmologist or non-ophthalmologist who has made a substantial impact and contribution to the development of eye banking,” was given to Gullapalli N. Rao, MD, Hyderabad, India. The fi rst Saiichi Mishima Award, recognizing “the most outstanding contributions and achievements in scientifi c research in the fi eld by a clinician or basic scientist in Asia,” was given to Teruo Nishida, MD, Yamaguchi, Japan. Finally, Congress president and chair of the organizing committee, Ma. Dominga Padilla, MD, Manila, Philippines, was nominated to deliver the Asia Cornea Foundation Lecture (Asia), a lecture “honoring an eminent Asian corneal clinician for his/her work in the fi eld of cornea.”

Standing on the shoulders of giants

Celebrating the meeting’s theme of “Expanding the Realm of the Possible,” Richard L. Abbott, MD, Mill Valley, Calif., USA, 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, MD (1903- 1987), and Max Fine, MD (1908- 1989).

Dr. Fine, who had been a mentor and sometime colleague of Dr. Abbott, was the fi rst 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 fi lm reels made by Dr. Fine in the 40s and 60s, Dr. Abbott had the fi lms restored and converted to a digital format, which he then presented to the audience at the opening ceremony of this 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 defi nite 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, he said, is whether a particular development is good for the patient.

Editors’ note: Dr. Abbott has no fi nancial interests related to his lecture.

Game changers

Since its establishment on March 17, 1994, the Eye Bank of the Philippines (later the Sta. Lucia International Eye Bank of Manila, SLIEB) has grown into a major supplier of corneal tissue for the region. From October 1995 to October 2012, the bank processed 18,272 corneas, of which 14,473 (79%) have been distributed.

But in August 2012, tragedy struck. A news report alleged: “Slain teen’s eyes taken for donation without family’s consent.” The allegations grew out of proportion, resulting in a signifi cant drop in the number of corneal tissue the bank was able to collect.

In her Asia Cornea Foundation Lecture (Asia), Ma. Dominga Padilla, MD, Manila, Philippines, described the experience. “It is diffi cult for me even to read the headline today,” she said.

The experience led her to contemplate the various “game changers” that allowed her and her colleagues to build the SLIEB to its stature before the incident, in the midst of a culture in which even the most outrageous allegations (“Eye Snatchers!” “Skulls cracked open to collect eyes!”), after 17 years of good work, could cause such signifi cant damage.

These factors include the International Federation of Eye and Tissue Banks (IFETB), legislation, the support of airline and courier services, the development of lamellar keratoplasty, media, and the establishment of the Asia Cornea Society and the Association of Eye Banks in Asia.

The experienced combined with the recognition of these factors led Dr. Padilla to a number of lessons she shared with her audience at this meeting, among them:

1.“Presumed consent” remains a valuable way to ensure an adequate supply of tissue, but the frequent education of partners and checking of details are important to ensure the system works.

2. Learn to utilize social media. In the months following the allegations, a virtual war has raged between what Dr. Padilla called “responsible media” and the “irresponsible media” that created the conflict.

Practical advice, but in the end, the incident highlights the cultural difficulties faced by eye bankers, who Dr. Padilla praised as the unsung heroes of corneal surgery.

Editors’ note: Dr. Padilla has no fi nancial interests related to her lecture.

Destigmatizing corticosteroids

Ophthalmologists today have a number of options for managing ocular surface and corneal infl ammatory disease, including nonsteroidal anti-infl ammatory 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, MD, Cincinnati, Ohio, USA, they are the most effective anti- infl ammatory agents, offering a broad spectrum of activity that provides the most comprehensive coverage of the infl ammatory cascade of any available agent. These agents suppress the migration of polymorphonuclear leukocytes (PMNs) and the reparative processes and functions of fi broblasts, 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 the delay in the normal course of healing that has been associated with the use of 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 fi rst 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 affi nity of dexamethasone—characteristics that signifi cantly alter the safety profi le of the drug.

While as effective as the current “gold standard” for steroid therapy—prednisolone—Dr. Holland said that loteprednol has signifi cantly less IOP response, making it ideal for long-term use.

Ophthalmologists, said Dr. Holland, need to rethink their aversion to corticosteroids, listing dry eye infl ammation, meibomian gland disease, chronic conjunctival infl ammation, 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 infl ammatory 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 resist-ance?

In managing keratitis, said John D. Sheppard, MD, 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-ciprofl oxacin 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 fi rst chlorofl uoroquinolone: besifl oxacin.

Bausch + Lomb’s formulation of the drug, Besivance (besifl oxacin ophthalmic solution 0.6%, Rochester, NY, USA) delivers the drug in a mucoadhesive vehicle of DuraSite, which helps keep the drug on the eye.

The molecular characteristics that make besifl oxacin 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 develop resistance.

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, PhD, Sydney, Australia, looked into the various risk factors affecting the incidence of keratitis.

Among the modifi able risk factors Dr. Stapleton examined, she found that using contact lenses 6 to 7 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.

Nonmodifi able risk factors include the initial 6-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 solutions, 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.

MANILA, DAY 2—The Asia Cornea Society’s 3rd Biennial Scientifi c Meeting continued with sessions that paint closely examined portraits of the cornea, including some surprising architectural details that almost certainly“expands the realm of the possible.”

Deconstruction, control, restoration

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 keratoplasty—Descemet’s membrane endothelial keratoplasty (DMEK)—but as the procedure is unrefi ned, 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 keratoplasty (DSAEK).

But while the advantages—less post-op astigmatism, better UCVA, BCVA, and survival than PK, etc.—are well-known, Donald Tan, MD, Singapore, president of the Asia Cornea Society, asked in his plenary lecture delivered Thursday morning: 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 diffi cult, 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, BC) Prof. Tan himself helped develop—has been about improving control.

And yet, often, 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 confi ned 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 diffi cult to control than the thinnest DSAEK.

Regardless, Francis J. Price, MD, Indianapolis, Ind., USA, 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 fi rst 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 ultra-thin 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 exagerrated 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 fi nancial interests in the device. Dr. Price has no relevant fi nancial interests.

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, MD, PhD, Nottingham, UK, 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 4 whole globes and 21 sclero-corneal discs. The paper, in press, was the subject of his plenary lecture at this 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 to 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 defl ates it; what’s more, after peeling, the surgeon can create a type 1 bubble in the remaining tissue.

Through subsequent histologic examination, Prof. Dua identifi ed 5 to 8 compact lamellae of type I 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 infl uence corneal curvature and biomechanics.

Editors’ note: Prof. Dua has no fi nancial interests related to his lecture.

ACS and The Cornea Society launch CorneaEd

“CorneaEd is, quite simply,‘cornea education,’” said Donald Tan, MD, Singapore, president of both ACS and The Cornea Society. The two societies, he said, have always had strong missions for education.

The website is a joint educational initiative of the sister societies, essentially a registry with links to fellowship programs in the Asia-Pacifi c and the U.S.

The aim is to reach out to young ophthalmologists looking for opportunities to train in the cornea subspecialty.

The idea, said Michael Belin, MD, Vice President for International Relations, Cornea Society, is to give young ophthalmologists the opportunity to fi nd programs that will give them experiences they might not otherwise have.

This in mind, the two societies hope to select two young ophthalmologists on the corneal fellowship program of their choice.

Applications will be available on the website in the fi rst quarter of 2013.

For more information and to access the registry, visit www. CorneaEd.org.

IKS massive undertaking for ACS

The Asia Cornea Society’s Infectious Keratitis Study (ACSIKS) is set to be a major game changer for the region. “Corneal blindness is big in Asia,” said Donald Tan, MD, Singapore, current president of The Cornea Society and the Asia Cornea Society.

It’s a fair statement, summarizing the significance of the most important cause of blindness in the region second only to cataract, but it barely scratches the surface, given the full scope and many nuances of the problem.

Most corneal disease in the world occurs in Asia, said Prof. Tan. Here, he said, corneal ulceration is a “silent epidemic.”

But the challenge of corneal blindness in Asia isn’t confi ned to magnitude; unsurprisingly for the region, huge variations exist from country to country, such that the problem runs the gamut of the entire spectrum of corneal infections.

Epidemiological patterns, for one, differ signifi cantly, said Prashant Garg, MD, Hyderabad, India. For instance, whereas studies have identifi ed contact lens use and ocular surface disease as the major risk factors for microbial keratitis in a developed region like Hong Kong, trauma is the most prevalent cause of infection in India, affecting a correspondingly different age group: most patients in India, said Dr. Garg, fall in the range of 20 to 50 years—the economically productive age group.

Wide variations also exist from country to country in terms of pathogen, environmental risk factors, the availability of drugs, antibiotic resistance patterns, access to treatment, and any number of other variables that have yet to be adequately quantified.

To this end, the ACS has embarked on the ACSIKS, a multicenter, prospective observational study in 11 study centers in eight major locations (China, India, Japan, Korea, Philippines, Taiwan, Thailand, and Singapore).

The study is intended to document the clinical management practices of doctors all over the region, while also collecting microbiological samples from recruited cases.

To date, said Prof. Tan, the study has recruited 2,118 cases, with preliminary data analysis of 1,544 of these cases. Preliminary analysis, he said has identifi ed fungal and bacterial pathogens to be the main causes of infectious keratitis in the region. EWAP

Editors’ note: ACSIKS is made possible by the support of Alcon (Fort Worth, Texas, USA/Hünenberg, Switzerland), Allergan (Irvine, Calif., USA), Bausch+Lomb (Rochester, NY, USA), and Santen (Napa, Calif., USA).

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