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News
The Ethics of Valid Consent for Organ Transplantation
According to the dead donor rule, patients must be deceased before any organ for transplantation may be removed. Current medical practice has adopted brain death and cardiac death as acceptable definitions of death. Robert D. Truog, MD, a professor at Harvard Medical School, and Franklin G. Miller, PhD, of the Department of Bioethics at the National Institutes of Health, argue that these definitions are "misleading" and "flawed," because these donors are not dead.1 Oftentimes, patients who are declared brain dead still have lower brain function, and those who experience cardiac arrest can be revived. In this sense, Drs. Truog and Miller wrote, "[the] medical profession has been gerrymandering with the definition of death to carefully conform with conditions that are most favorable for transplantation."1
In response to this ethical conundrum, Drs. Truog and Miller propose an alternative approach to vital organ donation that requires valid informed consent from patients or their surrogates in cases of irreversible neurologic injury. With valid consent, they state, no wrong is done in retrieving vital organs before death, provided anesthesia is administered. They assert that valid consent under the limited condition of devastating neurologic injury protects the patient, respects the wishes of those who wish to donate organs, and will expand the pool of eligible organ donors.
Given the prevalence and importance of corneal transplantation for sight-restoring procedures, Cataract & Refractive Surgery Today contacted members of the ophthalmic community for their reaction to Drs. Truog and Miller's proposal. Paul J. Dougherty, MD, agreed with their argument and expressed concern that "the many definitions of 'death' could be potentially manipulated by the organ transplantation industry." Dr. Dougherty is Clinical Instructor of Ophthalmology at Jules Stein Eye Institute, University of California at Los Angeles, and Medical Director of Dougherty Laser Vision Institute in Camarillo, California. In a situation of irreversible neurologic damage, consent from the donor or surrogate would remove the "definition" dilemma as well as create the best possible chance of survival for the individuals receiving an organ, Dr. Dougherty argued. "Rather than waiting until life-sustaining extraordinary measures like a ventilator have been withdrawn to remove the organs, it makes a lot more sense for the organs to be removed prior to withdrawing extraordinary life support to maximize the viability of the organs for transplantation."
Mark Packer, MD, agrees with Drs. Truog and Miller's assertion that "whether death occurs as the result of ventilator withdrawal or organ procurement, the ethically relevant precondition is valid consent by the patient or surrogate."1 The "obsolete abstract terminology" of the dead donor rule can conflict with personal wishes regarding end-of-life care, stated Dr. Packer, Clinical Associate Professor at the Casey Eye Institute, Oregon Health and Science University, and private practitioner at Drs. Fine, Hoffman & Packer, LLC. "Applying generalized or abstract definitions to individual, real-life situations involving ethical decisions inevitably creates untenable postures," he continued. "We can never specify every possible situation that may arise; thus, we must trust someone else to do the right thing when we cannot. Those trusted persons are our surrogates. We should allow love and empathy to guide their choices, within the broadest possible conception of individual freedom and justice."
Replacing the dead donor rule with valid informed patient or surrogate consent does not address the "misleading" and "flawed" definitions of death to which the medical profession currently adhere, asserted Lisa Brothers Arbisser, MD, in an e-mail to CRSToday. "I agree that the dead donor rule can no longer be strictly interpreted as a cold and stiff patient, [but] if we are to assist and prolong others' lives with useful organ transplantation, it seems to me that the most critical issue is to use a definition of death that is comfortable for the protection of public confidence."
Dr. Arbisser is in private practice at Eye Surgeons Associates in the Iowa and Illinois Quad Cities, and she is Adjunct Clinical Associate Professor at the John A. Moran Eye Center, Uni-versity of Utah, Salt Lake City. "Although ethicists are clearly still grappling with these issues, I believe that a socially acceptable definition of death is of utmost importance beyond any philosophical or medical definition," Dr. Arbisser wrote. "Viable organ procurement is certainly important to in-creasing [the] availability of tissue; however, any crisis in public confidence could radically decrease the likelihood of people choosing to become donors."
Anti-Infective Eye Drop Recommended for Approval
The FDA Dermatologic and Ophthalmic Drugs Advisory Committee voted unanimously to recommend the approval of besifloxacin ophthalmic suspension, 0.6%, (Bausch & Lomb, Rochester, NY), a broad-spectrum, anti-infective drop for the treatment of bacterial conjunctivitis. Besifloxacin is a novel fluoroquinolone that eradicates a broad spectrum of common bacterial conjunctivitis pathogens. Currently, the FDA advisory committee is reviewing besifloxacin as part of the approval review process for new drug applications. The product is due to come to market in the United States in 2009, according to a spokesperson from Bausch & Lomb.
Positive Results for Topography-Guided LASIK
The 6-month results of an ongoing FDA trial indicate that topography-guided LASIK is safe, effective, and predictable for the treatment of low-to-moderate myopia with astigmatism.1
The study, conducted at four centers in the United States, included 135 eyes of 68 patients with a spherical manifest refraction error ranging from -0.50 to -7.00 D and astigmatism ranging from 0.50 to 4.00 D. Researchers used the customized aspheric treatment zone ablation algorithm of the EC-5000 CXII excimer laser (Nidek Co. Ltd., Tokoyo, Japan) for all LASIK procedures.
At 6 months postoperatively, refractive and visual acuity outcomes exceeded the FDA's criteria for topography-guided LASIK, the investigators reported. The mean manifest refraction spherical equivalent in all eyes was -0.09 D ±0.31. No eye lost two or more lines of BSCVA. Out of 131 eyes, 116 (89%) had a UCVA of 20/20 or better. BSCVA increased by two or more lines in 21 eyes (16%), and 122 eyes (93%) had a manifest refraction spherical equivalent within ±0.50 D. The total ocular higher-order aberrations increased by 0.04 µm. Additionally, glare and halo symptoms were reduced.
"Topography-guided LASIK is the next revolutionary advance in laser vision correction," Paul J. Dougherty, MD, lead author of the study, wrote in an e-mail to Cataract & Refractive Surgery Today. Dr. Dougherty is Clinical Instructor of Ophthalmology at Jules Stein Eye Institute, University of California at Los Angeles, and Medical Director of Dougherty Laser Vision Institute in Camarillo, California. "This procedure is likely to replace Hartmann-Shack driven custom treatments because of its higher fidelity and ability to image and treat irregular astigmatism in a truly customized fashion with surgeon input. Unlike the currently available wavefront-guided custom lasers, which are based on 200 Hartmann-Shack data points that change every time the patient blinks, the CATz topography-guided treatments are based on almost 7,000 topographic data points with the type and amount of irregularity treatment determined by the surgeon."
Dr. Dougherty is a consultant to Nidek Co. Ltd.
Once-Daily Xibrom Achieves Statistically Significant Results
The results from a phase 3 clinical trial of once-daily Xibrom (bromfenac 0.09%; Ista Pharmaceuticals, Inc., Irvine, CA) suggest that the topical, nonsteroidal anti-inflammatory drug is effective for the control of ocular inflammation and pain after cataract surgery.
The phase 3 trial enrolled 282 patients who underwent cataract surgery. The study consisted of two identical US multicenter, randomized, double-masked, parallel-group, vehicle-controlled studies. The trials were performed under a common protocol and designated the east region trial (ER) and the west region trial (WR). Patients received either Xibrom or placebo once daily 1 day before surgery and continued for 14 days following surgery. Pain was assessed at 1 and 15 days after surgery.
The WR trial showed statistical significance in eliminating ocular inflammation 15 days after cataract surgery and ocular pain 1 day after surgery. The ER did not demonstrate statistical significance for these endpoints. A higher rate of discontinued patients and placebo effect for pain relief are possible reasons why the ER trial did not produce statistically significant results. The proportion of patients who did not experience photophobia was statistically significant in both the WR and ER studies, and no serious ocular or systemic adverse events occurred.
Ista plans to perform a confirmatory phase 3 trial of once-daily Xibrom in 2009. The FDA approved Xibrom in 2005 as a twice-daily formulation.
Dry Eye Drug to Begin Clinical Trials
Resolvyx Pharmaceuticals (Bedford, MA) plans to begin a placebo-controlled, phase 1/2 clinical trial of RX-10045 for the treatment of moderate-to-severe dry eye by the end of 2008. The company submitted an investigational new drug application to the FDA in early October 2008.
RX-10045 is an isopropyl ester prodrug of the active resolvin compound, RX-10008. In in vivo preclinical studies, RX-10045 prevented dry eye symptoms and restored healthy cellular function. According to the company, the drug was also effective for decreasing corneal inflammation, reducing corneal epithelial damage, and preventing the loss of goblet cells.
Team of Ophthalmic Surgeons Formed to Study Collamer
STAAR Surgical Company (Monrovia, CA) recently formed the Collamer Accommodating Study Team (CAST) to collaborate with STAAR on an evaluation of the baseline accommodative ability of the company's collamer lens technology. The team of seven ophthalmic surgeons will explore the accommodative properties of collamer over the course of three phases.
Phase 1 will begin with the scheduled 2009 launch of the Collamer Aspheric Single Piece Lens. Members of the CAST will collect data on near and distance visual acuity from patients who receive the lens. During phase 2, the CAST will evaluate the design changes of the new lens against the baseline accommodative data collected from phase 1. Phase 3 will involve a newly designed collamer lens that will undergo clinical study and submission to the FDA for approval in the United States.
Companies Partner to Test Drugs on Human Stem-Cell–Derived Corneal Tissue
International Stem Cell Corporation (ISCO; Oceanside, CA) is partnering with Absorption Systems (Exton, PA) to commercialize human stem-cell–derived corneal tissue for drug testing. According to a news release, the collaboration combines ISCO's parthenogenetic stem-cell–derived human corneal tissue with Absorption Systems' expertise in creating in vitro assay systems for drug testing.
ISCO stated that its corneal tissue, which includes cellular layers and structures found in the human cornea, is viable for toxicity testing in the laboratory. As a result of the collaboration, ISCO plans eventually to use its parthenogenetic stem cells to create cell transplant therapies for diseases of the eye. Both companies say that testing drugs in parthenogenetic stem-cell–derived human corneal tissue-based assays will reduce the use of laboratory animals currently necessary for these tests.
Surveys Reveal Global Burden of Presbyopia
Presbyopia affects more than an estimated 1 billion people globally, according to an analysis of multiple population-based surveys.1 That figure is projected to increase to 1.4 billion by 2020 and to 1.8 billion by 2050.
Of the 1 billion people currently affected by presbyopia, 517 million do not have adequate near vision correction. Four hundred ten million of these individuals (94% of whom live in developing countries) have a significant near-vision disability and could benefit from spectacles. According to investigators, patients' "access to spectacles in [developing] countries is limited by insufficient numbers of health care professionals able to perform relevant eye examinations, a lack of available, affordable spectacles, and a lack of adequate public health support structures to help people obtain spectacles."1 If spectacles are not made more accessible in these countries, researchers project that the number of individuals globally who will be disabled due to uncorrected presbyopia will increase to 563 million by 2020.
Researchers stated that additional epidemiological study is needed to generate a more accurate global estimate of those affected by presbyopia. Based on their findings, however, the investigators recommended that "a provision of human resources, affordable spectacles, and systems of delivery" be instituted in developing countries to help combat the growing visual problem in these regions.1 Additionally, they proposed that primary eye care include refractions as well as evaluations for glaucoma and diabetic eye disease, because patients with these diseases are generally affected by presbyopia.
More Effective Dry Eye Therapies Desired
Most (94%) of the 245 ophthalmologists who participated in a recent survey sponsored by Aton Pharma, Inc. (Lawrenceville, NJ), felt that more effective therapies for moderate-to-severe dry eye are needed. Only 5% of respondents rated current therapies effective for severe dry eye. Participants in the survey reported that, over the course of a year, they prescribe, recommend, or suggest an average of 1.9 different treatment approaches for each patient with mild dry eye, 3.2 treatment approaches for each patient with moderate dry eye, and 4.9 treatment approaches for each patient with severe dry eye.
Participants were also asked about their primary treatment goals for moderate-to-severe dry eye patients. Maintaining and protecting the ocular surface was ranked as the primary or secondary goal by 74% of respondents, and lubricating and hydrating the ocular surface was ranked as the primary or secondary goal by 67%. When selecting treatment products, the surveyed ophthalmologists identified a product's ability to provide continuous relief (84%) and its ability to be used long term by a patient (74%) as most important. Other considerations included dosing frequency (66%), the length of time preserving the tear film (66%), and the length of time to effectiveness (63%).
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