At Press Time

Multiple Uses From One Donor Cornea

By Jerry Helzner, Senior Editor

■ A recent journal article highlights the fact that German researcher Claus Cursiefen, MD, who is also affiliated with Harvard School of Medicine, achieved good results with a surgical strategy that uses a single donor cornea to help two patients with differing corneal diseases.

With the supply of donor cornea tissue an increasing concern worldwide, Dr. Cursiefen's news is welcomed by the corneal transplant community. However, he is not alone in extending the use of donor corneas. American transplant pioneer Mark Gorovoy, MD, the inventor of DSAEK, who cuts his own tissue, reports that he has been able to help as many as four patients with the tissue from a single cornea.

Dr. Cursiefen's new approach restored good vision to patients who had either Fuchs' dystrophy or keratoconus. The study appears in the February issue of Ophthalmology.

Advanced keratoconus is often treated with deep anterior lamellar keratoplasty (DALK). Fuchs' dystrophy and similar diseases can be treated via several surgical techniques, including the newer Descemet's membrane endothelial keratoplasty (DMEK). Dr. Cursiefen's team noted that, once the tissues needed for DALK were removed from a donor cornea, the precise tissues needed for DMEK remained. They reasoned that scheduling two patients for surgery on the same day, with the DALK patient always first, would make it possible to use one cornea for two patients. Since about 80% of the corneal diseases that require transplants can be treated with DALK or DMEK, this approach could nearly double the available corneal tissue supply and make timely treatment available to many more patients.

“In this exploratory study, we were able to use one cornea to successfully treat two patients, for 10 of 12 consecutive donor corneas,” Dr. Cursiefen said. “Only twice during surgery did we find that a full corneal transplant, rather than DALK, was needed. Our early follow-up with all patients shows good visual outcomes and few complications.” At six-month follow up, successful DALK patients achieved, on average, 20/35 vision, and DMEK patients on average achieved 20/31 vision.

When cut carefully, one donor cornea can serve several purposes.

Drawbacks are that both DALK and DMEK are demanding surgeries that currently can only be performed at leading-edge ophthalmic hospitals, and, because both techniques are relatively new, longer-term outcomes and effectiveness remain to be determined. Also preparation and care of the split corneas requires sophisticated planning and preparation, and access to additional corneas is essential in case full transplants becomes necessary. Further research is needed.

Commenting on this technique, Steven Silverstein, MD, an experienced cornea transplant surgeon based in Kansas City, Mo., says that although most transplant surgeons are doing DSAEK, very few at this point are doing DMEK. “It is technically more difficult, with a minimum—at this point in the learning curve—of potential visual improvement over DSAEK,” he says. “It is still too early to tell whether it will go mainstream and replace DSAEK as the technique improves.” Also, he says, care must be taken in cutting donor tissue to not damage the endothelial cell layer.

From a practical standpoint, Dr. Silverstein says both patients would typically need to be scheduled on the same day at the same facility, and have differing needs.

“It is true that the tissue shortage abroad is huge, and this would be an even bigger opportunity for European, Asian and third-world countries,” asserts Dr. Silverstein. “It is not technically challenging to separate the layers of the cornea for the two procedures. What is novel here is that they have deliberately studied the feasibility of using tissue in this manner to spread the availability of tissue.”

And this from Dr. Gorovoy:

“I believe that is the way to go to, not only to save tissue, but also to control costs. This is discouraged in the United States, as the corneas [that come from eye banks] are for single use, but I know of several of us who use the tissue for multiple patients.”

Dr. Gorovoy notes that donor cornea can be used for both lamellar grafts and covering tube shunts with cornea tissue.

“Occasionally, the tissue can even be used for emergency patch grafts,” says Dr. Gorovoy, “so it is possible one cornea could actually help four patients. If this is done, it is important the surgeon keep logs of the tissue and recipients, but I am not aware of any adverse sequelae to date.”

Punctal Plug Drug Delivery Fails Trial

QLT study was for allergic conjunctivitis.

■ QLT Inc. has announced disappointing results from a phase 2 proof-of-concept clinical trial for the olopatadine punctal plug delivery system (O-PPDS) for allergic conjunctivitis. However, the company continues to study punctal plug delivery for glaucoma medications.

Interim results from the randomized, placebo-controlled, double-masked phase 2 trial have shown that O-PPDS is generally safe and well tolerated in subjects with allergic conjunctivitis. An analysis has been performed on data from subjects in Group 1 of the study, in which the PPDS (O-PPDS or placebo-PPDS) was placed in subjects' lower puncta bilaterally for four days. Subjects were then exposed to ragweed allergen for four hours in an environmental exposure chamber (EEC). Itching and other signs and symptoms of allergic conjunctivitis were assessed during the four-hour EEC session. Following a 12-day washout period, the subjects were then assessed during an EEC session after treatment with Patanol or placebo eye drops.

QLT says the data demonstrate that there were no significant differences noted between the O-PPDS and placebo-PPDS subjects with respect to reduction in the signs and symptoms of allergic conjunctivitis, with both cohorts showing similar improvements. Internal study controls, including the olopatadine and placebo eye drop cohort responses, also failed to confirm the model's efficacy relative to the trial design.

“These equivocal results from the first trial examining the potential utility of sustained low-dose olopatadine delivery in the eye support the notion that the EEC model, as utilized in the conduct of this trial, was not sufficiently sensitive to adequately demonstrate the potential benefit of the O-PPDS in patients suffering from allergic conjunctivitis,” said Dipak Panigrahi, MD, senior vice president of research and development, and chief medical officer of QLT. “Given these findings, we have decided to stop the current study at this time.”

“We are disappointed that the O-PPDS study model could not generate definitive clinical results; however, we plan to continue to evaluate alternative study designs for the O-PPDS,” said Bob Butchofsky, president and CEO of QLT. “We do not plan to begin further clinical trials of the O-PPDS pending the outcome of our ongoing Latanoprost-PPDS trial in glaucoma.”

California MDs in Scope-of-Practice Battle

Physicians: ODs not adequately trained to treat glaucoma.

By Samantha Stahl, Assistant Editor

■ Two California physician groups are fighting recently approved regulations to certify optometrists to treat glaucoma. Optometrists previously won the right to treat limited types of the disease by claiming that some rural areas of the state were underserved by ophthalmologists and that ODs could be trained to treat glaucoma effectively and cover those gaps. They recently pushed for a revised certification process, charging that the prior process was too difficult.

The California Medical Association and California Academy of Eye Physicians and Surgeons, who filed suit on January 11 against the California State Board of Optometry, fear that the new standards allow ODs to be certified to independently treat glaucoma are now too weak.

The physicians also cite a case involving a VA facility in Palo Alto in which 87 glaucoma patients were reassigned to ophthalmologists after allegations of substandard care provided by optometrists.

The new rules, which went into effect on January 8, now allow an optometrist to be certified to treat glaucoma without ever having to directly treat a glaucoma patient with medication during the training process. Prior regulations had optometrists treat 50 patients over two years, each under the supervision of an ophthalmologist.

“We feel that the new standards were not developed in a way that protects patients. Patient safety is number one,” says Craig Kliger, MD, executive vice president of the California Academy of Eye Physicians and Surgeons. The organization put forth proposals to the Department of Consumer Affairs last year for alternative certification requirements, recommending that optometrists treat patients from their own practices as part of the certification process to get actual management experience rather than just examine patients in a group setting and develop treatment plans for those patients that would never get executed. It is unclear whether the Department seriously considered the proposal.

In general, the requirements in question ask optometrists to complete two of the following: A 16-hour lecture-based case management course, a 16-hour grand rounds program of examining (but not treating) live patients, and/or a preceptorship program where the optometrist must co-manage patients with a certified optometrist or ophthalmologist.

Dr. Kliger says, “We believe we have a strong legal case and are hopeful that the regulations will be voided in the interest of patient safety.”

Research Digest

New & Noteworthy Journal Articles

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Anti-VEGF for glaucoma. Adding to a growing body of evidence for the use of anti-VEGF agents in neovascular glaucoma (NVG), the February 2011 issue of Archives of Ophthalmology features the results of the largest prospective trial of intravitreal bevacizumab in NVG.

Ophthalmologists in London treated 52 eyes in 50 patients with NVG with an intravitreal injection of 1.25 mg bevacizumab and then followed them up for six months. They used subjective pain scoring as their primary outcome, and also measured IOP and iris neovascularization at each monthly visit.

Of the 44 patients who finished the study, subjective pain scores reduced by a statistically significant degree just a week following the injection, with this relief extending throughout the six-month period of follow-up. Iris neovascularization also decreased to a significant extent, but this decrease was transient and tended to rebound by the end of follow-up. While there was a reduction in the number of topical glaucoma medications required after treatment with bevacizumab, 31 eyes still required insertion of a drainage device to decrease IOP. However, this was viewed as successful treatment, given that IOP was reduced over the follow-up period in 100% of the eyes studied.

A baffling aspect of the study is that pain was reduced significantly after injection of bevacizumab, but the injection alone seemed not to reduce IOP. Thus, a commonly deduced connection between pain and IOP elevation may be overestimated, and inflammation and its reduction may play a role in pain abatement. While more studies are needed, at the very least, this study suggests that intravitreal bevacizumab may help to reduce complications in IOP-lowering surgery in patients with NVG.

► Steroids for DME. Is the treatment of diabetic macular edema using peribulbar injections of triamcinolone acetonide safe? Laser is still the standard of care for DME, but steroids have gained ground, particularly with the approval by the FDA of Allergan's Ozurdex intravitreal insert containing dexamethasone for the treatment of macular edema consequent to retinal vein occlusion and the likely approval, therefore, of other steroid treatments for other forms of edema. A team of retinal physicians from the National Eye Institute in Bethesda, Md., take up this question in the February 2011 issue of Retina.

Data were gathered from six eyes that had been treated for DME using triamcinolone over a two-year period. IOP increased by more than 10 mm Hg in 17 eyes. Furthermore, another six patients required phacoemulsification by the end of the two-year period due to steroid-induced cataracts. These results were gathered from four treatment groups determined by dose of triamcinolone (20 mg or 40 mg) and whether the injection was followed by treatment with laser.

The authors of the study conclude that peribulbar injections are associated with increased incidence of elevations in IOP; this result appears to be more relevant with regard to anterior injections. However, ptosis is a more common adverse event with posterior peribulbar injections, so doctors must proceed with caution. Although the sample size used in this study was quite small, the study is the longest prospective study of its kind, and the authors believe its results may have implications for steroid use across retinal disorders.

► Sight for sore eyes? With the herpes simplex virus type 1 (HSV-1) a major cause of vision loss due to corneal complications, a group of investigators from New Orleans have examined the theory that the cornea is a reservoir for the latent virus. They report their findings in the March 2011 issue of Cornea.

The authors conducted a meta-analysis of more than 50 research articles published in peer-reviewed journals. The literature included studies carried out on mice, rabbits and non-human primates, as well as humans. In particular, the authors examined the issue of whether herpes keratitis (HK) can be activated by latent viruses following penetrating keratoplasty (PK), after which HK is a common complication.

Based on their research, the authors believe that the human cornea is a potential site for HSV-1 latency. However, they concede that their conclusion is far from authoritative, particularly given the several studies they analyzed that found only low percentages (some as low as 17%) of latent virus in human cornea samples that had shown symptoms of HK. The authors hope that, with better screening technology, HK following PK can be decreased or eliminated.

► Britain is burning. The February 2011 issue of the British Journal of Ophthalmology features two papers on the treatment of acute ocular burns, as well as an editorial on the topic. In the editorial, Jean-Jacques Gicquel, MD, of Poitiers, France, reviews the first aid treatment of ocular burns, dividing the discussion into the agent causing the burn (acid vs. alkali) and covering the transition from emergency care to long-term management.

The first article, covering research carried out by physicians in New Delhi, India, compares two prognostic classification systems, finding that the Dua classification system introduced in 2001 is superior to the older Roper Hall system, particularly because the Dua system subdivides the Roper Hall grade 4 burn category into further categories.

The second paper, also from New Delhi, details the transplantation of amniotic membrane in eyes with acute ocular burns and notes that the procedure leads to faster healing of epithelial defects in moderate burns. However, there are no other advantages to the procedure that could be identified. OM