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Ophthalmic use of amniotic membrane promising, but adequate study data lacking
Find our coverage of this news item and other cornea highlights from the World Ophthalmology Congress below.
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HONG KONG — The precise benefits of amniotic membrane application in various ocular disorders have not been adequately studied, according to a researcher here at the World Ophthalmolgy Congress.
Harminder S. Dua, MD, PhD, said despite the fact that many success stories regarding the therapeutic value of amniotic membrane have been circulated, there are strikingly few randomized clinical trials published in the literature.
“If you put ‘amniotic membrane’ and ‘randomized controlled trials’ and ‘eyes’ [into a PubMed digital archive search], you only get 15 trials,” said Dr. Dua, the president of the European Association for Vision and Eye Research.
These trials have been conducted in glaucoma, pterygium, acute ocular burns and refractory neurotrophic corneal ulcers.
When looking at the statistical significance of these trials, “not one has shown amniotic membrane to be better than the existing alternative, and some have shown amniotic membrane to be worse than the existing alternative,” he said.
 Harminder S. Dua, MD, PhD, (left) and Shigeru Kinoshita, MD, discussed amniotic membrane and its potential clinical applications at the World Ophthalmology Congress. Image: Wolkoff L, OSN | ||
He added that those who claim its benefits must establish a purpose and an objective to the study, and only when both of these are achieved can they claim success.
Dr. Dua said one of the major drawbacks of amniotic membrane use for ocular disease is that there is no standardization of factors such as which part of the membrane to use, who the donor is, when the membrane is taken and whether the mother has had any previous births.
“There are so many variables we don’t consider when we take this membrane and use it … around the world. It is not proper science,” he said.
Dr. Dua said the answer might lie in the future development of a synthetic membrane that incorporates the growth factors, anti-inflammatory and healing properties, and other benefits of amniotic membrane.
“The future is bright because we have learned from amniotic membrane and now we can move forward,” he said.
Dr. Dua’s talk came on the heels of several talks on the ophthalmic use of amniotic membrane.
Ashley Behrens, MD, discussed the ophthalmic applications of amniotic fluid, which has been studied as a possible replacement for amniotic membrane in ocular surface disease. Although this clinical use is still experimental, Dr. Behrens is optimistic about its possible ability to promote re-epithelization, control inflammation, inhibit neovascularization and kill bacteria.
Only two human patients — both with severe dry eye — have received amniotic fluid in the eye outside the United States. A multicenter clinical trial will be under way soon, he said.
In another presentation, Shigeru Kinoshita, MD, discussed the use of cultivated oral mucosal epithelium in tandem with amniotic membrane transplantation for conjunctival fornix reconstruction. He and colleagues have utilized this approach in about 12 patients, with promising results, he said.
Although they are not certain that the regenerated conjunctival cells are coming from the transplanted mucosa, he said the “surgical strategy could improve long-term prognosis, may protect residual corneal stem cells and suppress cicatrization.”
These items appeared originally as daily coverage from the meeting on OSNSuperSite.com. Look for more in-depth coverage of these and other topics in upcoming issues of Ocular Surgery News.
Precipitate development impedes endophthalmitis treatment effectiveness
Because of precipitate development that may effectively block up to 94.9% of ceftazidime absorption when mixed with balanced salt solution, one researcher recommended the exploration of the use of newer antibiotics in combination with vancomycin for the treatment of endophthalmitis.
Mamie Hui, FRCPath, of the department of microbiology at the Chinese University of Hong Kong, said a checkerboard analysis found ceftazidime concentration fell to 94.9% by 48 hours when mixed with balanced salt solution with or without vancomycin.
Researchers theorized that precipitate formation blocked the absorption of ceftazidime. Dr. Hui performed an equilibrium dialysis study to test this theory. The tests used an equilibrium dialyzer, a simple cylindrical instrument composed of two chambers separated by a semi-permeable membrane filled with donor vitreous and incubated at 37° C. Ceftazidime and vitreous were added to one chamber, and aliquots were taken at regular intervals from the other chamber.
“Ceftazidime concentration fell to an extremely low level at 48 hours,” Dr. Hui said. “Such a level may not be sufficient for organisms with high ceftazidime [minimum inhibitory concentration] levels, such as Pseudomonas, Acinetobacter, Citrobacter, Enterobacter.”
Dr. Hui carried out the same analysis with other gram-negative affecting agents. Both ciprofloxacin and amikacin were found to have a much higher concentration at 48 hours (greater than 30%).
Dr. Hui said although intracameral use of such agents is not commonly practiced, it should be considered in light of this research.
Advanced surface ablation superior to LASIK in post-PK patients at 3 months
Advanced surface ablation with mitomycin-C has shown a trend toward visual improvement in ametropic patients who have undergone penetrating keratoplasty, according to a presenter.
Michael A. Lawless, MBBS, FRACO, FRACS, FRCOphth, presented 3-month results from a study involving 44 eyes of 16 women and 26 men who had previous PK. Dr. Lawless and two colleagues, Gerard L. Sutton, MBBS, FRACO, FRACS, and Christopher M. Rogers, MBBS, FRACO, FRACS, performed surface ablation using two excimer lasers: the LADARVision 4000 and LADAR 6000 platforms (Alcon) in 29 cases and the Allegretto (WaveLight AG) in 15 cases.
They applied mitomycin-C 0.02% with an 8-mm corneal sponge for an average of 35.45 seconds. Dr. Lawless reported on outcomes at 1 month and 3 months follow-up, noting an overall trend toward improvement. He also said 100% of patients remained in the study through the 3-month follow-up period.
Preoperatively, patients had a mean sphere of –1.41 D, –4.93 D cylinder, –4.22 D spherical equivalent, 46.42 D average keratometry value and a central corneal thickness of 627 µm. At 3 months, mean sphere had improved to –0.64 D and cylinder was –2.26 D. Average keratometry value was 44.28 D at 3 months and central corneal thickness was 485 µm.
Dr. Lawless also said there was a trend toward improvement in best corrected visual acuity, in that 25% of eyes had 20/20 vision at 3 months postoperative compared with 10% preoperatively.
“There is a trend toward improvement in visual acuity, and that trend tends to increase with time,” he said. “We had excellent follow-up at 3 months, and that tends to trail off, but anecdotally, certainly [the improvement in visual acuity] with surface treatment continues at 12 months.”
Dr. Lawless compared these results to a previous study he helped conduct that evaluated LASIK to treat myopia and astigmatism after PK. That study, published in 1999 in the British Journal of Ophthalmology, evaluated 26 eyes that underwent LASIK with a variety of microkeratomes. In comparing the 3-month results of both studies, Dr. Lawless and colleagues found the results with advanced surface ablation to be superior.
“If you go to 3 months … there is a statistically significant difference. [Advanced surface laser ablation] patients were statistically better than LASIK patients in spherical equivalent and refractive astigmatism,” he said.
Intracameral cefuroxime is best option for endophthalmitis prophylaxis, physician says
Despite the fact that topical fluoroquinolones have become standard of care in the United States, intracameral perioperative antibiotic injections are the best route for prevention of postoperative endophthalmitis, according to a speaker.
 Peter Barry |
Peter Barry, FRCS, made his case for why intracameral cefuroxime, and not topical fluoroquinolones, should be the standard of care for surgical prophylaxis during Cataract and Refractive Surgery Subspecialty Day.
“There can never be an ideal antibiotic for prophylaxis. Cefuroxime is the best for now,” Dr. Barry said.
He said cefuroxime is an old drug and is not effective against methicillin-resistant Staphylococcus aureus, Enterococcus and Pseudomonas. Furthermore, it is inexpensive and, therefore, is not a feasible financial option for a company to produce in the high numbers necessary. It is also not approved by the U.S. Food and Drug Administration.
The efficacy and safety of cefuroxime have been proved in more than 8,000 patients who received the drug in the European Society of Cataract and Refractive Surgeons endophthalmitis study and in a study of 425,000 Swedish patients conducted by Mats Lundstrom, MD, and colleagues.
“Importantly, emerging resistance to fourth-generation fluoroquinolones would argue against their role in the future,” Dr. Barry said.
He noted that he believes that the popularization of latest-generation antibiotics such as gatifloxacin and moxifloxacin is too little too late, based on reports of their emerging resistance and on the use of the drugs in animal husbandry.
Dr. Barry said a study evaluating the efficacy of topical fluoroquinolones in a large cohort of patients would be desirable to provide an evidence-based standard for surgeons. Yet the prospect is “out of the question.”
“You would need an enormous number of patients to prove equivalence, the cost would be prohibitive, recruiting patients would be difficult and the study would be superfluous unless … there is something wrong with cefuroxime,” he said.
Dr. Barry also outlined the results of the ESCRS endophthalmitis study, the results of which were released at the society’s 2006 meeting in London. The study, which enrolled about 16,000 patients, found that cefuroxime injection lowers the chances of bacterial contamination by a factor of 5.
“This means that the risk rate is reduced to less than five in 10,000 cases,” Dr. Barry said. He noted that the rate of infection, which was criticized in an editorial in Ophthalmology, is consistent with the Swedish study conducted by Dr. Lundstrom and colleagues.
MMC assists in preventing recurrence of neoplasia
The use of adjunctive mitomycin-C in addition to excision provides the best chance for preventing recurrence in localized conjunctival intraepithelial neoplasia, a surgeon said.
“It should be considered as adjunctive therapy in the treatment of primary and recurrent disease,” James Muecke, MD, said. “It may be used as monotherapy in diffuse disease and fine lesions not amenable to excision, but close, ongoing follow-up is recommended in view of the significant risk of recurrence.”
Dr. Muecke presented the data from a prospective, noncomparative case series of 104 patients. The patients all had localized lesions and were treated over a 9-year period.
The patients were divided into three treatment groups: localized lesions that were either thick or fine, diffuse lesions and recurrent lesions.
Localized thick lesions were excised and treated with cryotherapy and then MMC 0.04% four times a day for 7 days; the cycle was repeated through two courses with 1 week treated and 1 week of rest. Localized fine lesions were treated initially with the same MMC cycle for two to three courses.
Diffuse lesions were treated with the MMC course of treatment over three courses. Recurrent localized lesions were excised, treated with cryotherapy and then treated with three courses of the MMC cycle.
Of the 86 eyes with localized lesions, one eye had a recurrence, for a rate of 1.2%. In the diffuse group, of the 10 eyes, two recurred and two were persistent, for a recurrence rate of 40%. In the already recurrent group of eight eyes, none recurred. “Overall there was a better control of local compared with diffuse disease,” Dr. Muecke said. “The best overall control was with excision and mitomycin-C of localized disease.
“I feel like excision remains an important step in this group, but primary excision rate alone has a high recurrence rate,” he said.
When MMC is used as an adjunct, Dr. Muecke advocated using the highest tolerable concentration with the week-on, week-off course of treatment to minimize toxicity to healthy cells.
Dr. Muecke said there were no major complications, but there was a high incidence of allergy.
DALK rapidly overtaking PK in terms of safety, outcomes
Deep anterior lamellar keratoplasty is fast becoming the procedure of choice because of its excellent visual results and safety profile, according to a surgeon.
Donald T.H. Tan, MBBS, FRCSG, FRCSE, FRCOphth, FAMS, said his utilization of penetrating keratoplasty has declined dramatically in favor of deep anterior lamellar keratoplasty (DALK). “I now only do PK for 25% of my patients. So this shift is occurring quite rapidly,” Prof. Tan said.
The indications for DALK are varied, and the procedure can be done in most cases in which PK would be indicated. He said in other parts of Asia, tectonic and therapeutic grafts are becoming increasingly prevalent.
Prof. Tan and colleagues conducted a cohort study evaluating 21 consecutive cases of therapeutic DALK (15 months follow-up), 89 nonperforated cases of therapeutic PK (23 months follow-up) and 20 perforated cases of therapeutic PK (14 months follow-up). The 21 cases of therapeutic DALK included cases of severe infection. Notably, none of these cases developed postoperative endophthalmitis. In contrast, in the therapeutic PK groups, 64% developed endophthalmitis.
DALK also has been shown to offer a better graft survival rate than PK as well as better visual results.
In another study, Prof. Tan said he and colleagues compared results from PK and two DALK techniques in 128 patients. The three groups included 64 PK patients, 31 manual DALK patients and 33 automated DALK patients.
Visual results were better with automated DALK than with either manual DALK or PK, Prof. Tan said.
Trachoma elimination initiative requires dedication of resources, behavior changes
The elimination of trachoma in poor countries hinges, in part, on the international political will to dedicate resources toward improving hygienic conditions, a speaker said.
Hugh R. Taylor, MD, FRACO, said the improvement of hygiene is a daunting task, but it is a necessary component toward eradicating the blinding disease, which affects an estimated 84 million people in the Third World. These are predominantly in Africa, as well as in Latin America and parts of Asia and Australia.
“The challenge of facial cleanliness is that behavioral change is hard to get,” Dr. Taylor said. “People will buy Coca-Cola, people will buy iPhones, but when you want people to change their behavior, it is tough. You have to be clever like Apple or Coca-Cola.”
Another major challenge to halting its spread is the scarcity of water in areas of poverty.
“People who view water as a very scarce resource aren’t going to waste water on just washing their kid’s face,” he said.
Dr. Taylor outlined the SAFE program, a global strategy recommended by the World Health Organization to attack the four main challenges involved with fighting trachoma: surgery, antibiotics, facial cleanliness and the environment.
Surgical remedies for trachoma tend to be ineffective because the disease badly damages the ocular tissue, making it difficult to operate. Also, there is great surgeon variability and a high recurrence rate. The distribution of antibiotics is also a major challenge because there are millions of people to treat, and distribution costs are high, he said.
Facial cleanliness remains the greatest challenge, and the environmental component to the SAFE program involves making large-scale improvements and investments in water supplies, latrines, insect control and housing, he said.
“We understand the disease,” he said. “What we need now is the commitment and resources to fully eliminate this blinding disease.”
A note from the editors:
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