Article Date: 7/1/2009

Proceed With Caution: When to Adopt New Ideas and Techniques?

Proceed With Caution: When to Adopt New Ideas and Techniques?

PAUL STERNBERG, JR., MD · FRANCO RECCHIA, MD · BRIAN R. CARLSON, MBA, MHSA

Paul Sternberg, Jr., MD, is George W. Hale Professor and Chairman of the Vanderbilt Eye Institute. Franco M. Recchia, MD, is associate professor of ophthalmology and chief of the retina division at the Vanderbilt University School of Medicine in Nashville. Brian R. Carlson, MBA, MHSA, is an administrator at the Vanderbilt Eye Institute. None of the authors has any financial interests in any products mentioned in this article. Dr. Sternberg can be reached via email at paul.sternberg@vanderbilt.edu.

Each year, dozens of new ideas are presented at various retina meetings, including innovative surgical techniques, novel off-label uses of medication, or creative treatment regimens. As a physician sitting in the audience, one is often quite excited by the concept and impressed by the potential impact of a new treatment. And one can usually think of a specific patient or two that fit the clinical scenario and would seem to benefit. But how does one decide whether to modify one's own patient care management plans based on what has just been presented?

Often the speakers are prominent clinicians presenting new approaches to clinical problems, but perhaps with small numbers of patients and limited follow-up. Over the years we have heard surgeons talk about procedures like submacular surgery, macular translocation, chorioretinal laser anastomosis, and radial optic neurotomy. All of these are fairly dramatic invasive procedures, but their "extreme" nature was considered acceptable in the face of the dismal natural history of the conditions for which they were developed.

A natural response to such presentations is excitement. So, too, is some degree of reservation about the premature nature of the work. Many of us will return from a meeting to our offices and immediately start doing these cases. We may travel to observe the surgery first, but often we will simply buy the instruments and start doing the procedure. These quick adoptions have been reflected in the ASRS's annual Preference and Trends survey, where some of these techniques were tried by more than 50% of the membership in the year subsequent to their introduction.

It is of interest that none of the aforementioned surgical treatments have been proven efficacious, and all have fallen out of favor, either proven ineffective by larger studies or supplanted by superior therapies. Another example is intravitreal triamcinolone for diabetic macular edema (DME): roundly adopted, advocated, and then demonstrated by the Diabetic Retinopathy Clinical Research network to be no more effective than laser as monotherapy for DME.1

Current meeting agendas are filled with different physicians proposing a myriad of protocols for monitoring the efficacy of antiangiogenic therapy, with the apparent goal of optimizing benefit while minimizing the number of injections. To date, none of these protocols have shown validated results comparable to those obtained from monthly injections for 2 years. In addition, we hear discussions of various strategies for managing the patient who is "unresponsive" to standard monthly injections of ranibizumab, including a resurgence of interest in photodynamic therapy.

On the other hand, some of us remember the first meetings at which vitrectomy with posterior hyaloid removal was reported as a successful treatment for idiopathic macular holes. Prior to this presentation, there was no treatment for this condition and patients were told they had permanent vision loss. Ironically, when this surgery was first described, some even questioned the integrity of its proponents, suggesting that they were showing preoperative photos as their postoperative results, and describing the surgery as the Emperor's New Clothes. Granted, visualizing the evanescent posterior hyaloid and internal limiting membrane can be quite difficult. However, this surgery proved highly effective and a planned randomized clinical trial was never completed because it was so obvious that the surgery worked.

More recently, we have heard of the efficacy of indirect diode laser photocoagulation for retinopathy of pre maturity and the promise of intravitreal bevacizumab for neovascular age-related macular degeneration. In both cases, encouraging preliminary clinical results, grounded in biological rationale, led to rapid adoption, application, and acceptance. Both treatments have improved quality of life for thousands of patients. Both treatments have become the standard of care in many parts of the world. Neither treatment, however, has been validated by any controlled clinical trial.

Evidence-based medicine has become the mantra of physicians, policy makers, and the public. Clinical recommendations based on multicenter, randomized controlled clinical trials are ideal, but are simply impossible for every clinical situation. Studies of common diseases cannot account for all permutations in clinical history and presentation, and studies of uncommon diseases may never achieve statistical power to yield significant results. With the exponential increase in drugs and devices, no study can include all combinations and comparisons. Practically speaking, we (and our patients) are rarely willing or able to wait the many months necessary to acquire the necessary evidence. And realistically, it is impossible to know it all. An editorial in the British Medical Journal in 1996 suggested that, in order to keep abreast of advances in general medicine, one would need to examine 19 articles per day, 365 days per year.

In reality, most of us spend about an hour per week reading the journals.2 And in the 13 years since that report, the number of relevant publications has increased dramatically! Physicians now receive information from more varied sources than ever before: still peer-reviewed journals and CME-regulated scientific meetings, but also non peer-reviewed or "throwaway" publications, electronic sources, pharmaceutical and surgical representatives, promotional talks at lunches and dinners, direct mailings, etc. As a result, we must do a yeoman's job to screen information sources, sorting through the financial and legal environment to assess the scientific and clinical value of a presentation.

Figure 1. Submacular surgery was introduced in the early 1990s as a treatment for subfoveal CNV that had the potential for sparing the damage to the overlying neurosensory retina seen with laser photocoagulation. After receiving much attention, its efficacy was not demonstrated in the Submacular Surgery Trials.

So how then do we make a decision about whether and when to adopt a new procedure? What steps can we take to ensure that are acting responsibly and reasonably? And what issues should we keep in mind as we contemplate new practices?

Knowledge is power, and there is no substitute for good information. While there are valuable ideas and opinions to be gained from a variety of sources, articles in scientific journals have withstood the process of peer review and generally carry more credibility. Meta-analyses, review articles, or comprehensive analyses of published literature (such as Cochrane Reviews or the American Academy of Ophthalmology's Ophthalmic Technology Assessments) are helpful in painting the "big picture." When a new treatment looks promising, it bears deeper investigation. A visit to the pioneering physician, to observe the technique, to discuss its nuances and evolution, and to observe patients in follow-up, can be valuable and educational. After trying a new technique, it is important to monitor one's outcomes, to make sure make sure that it is truly a benefit to patients and that there are not unforeseen complications. Sharing these results is an integral part of building a collective experience and broader knowledge.

Figure 2. This patient with idiopathic subfoveal choroidal neovascularization underwent successful limited macular translocation surgery, with vision improving from 20/100 pre-operatively (left) to 20/40 postoperatively (right). The technique received great acclaim with special instruments designed and sold; however, its benefit over natural history, laser, or newer techniques like photodynamic therapy and antiangiogenic therapy was never successfully proven in a randomized clinical trial.

Critical thinking is critical to success. Even papers in respected journals, and talks by honored lecturers, will have flaws, and the skills honed in journal clubs during training will help to assess the integrity of the method and the validity of the results. One must think about the science and the biological plausibility behind the treatment. Often, there is good justification for a procedure from clinical observations, histopathologic studies, or laboratory research. For example, biomicroscopic evidence of the progression of idiopathic macular holes suggested the role of vitreomacular traction and implied a therapeutic role for vitrectomy with hyaloid removal.3 Histopathologic differentiation of choroidal neovascular complexes located anterior or posterior to the retinal pigment epithelium (so-called type 1 or type 2 membranes) suggested that certain patients would be more likely to benefit from submacular surgery.4

Critical thinking is also needed in cases in which new treatments may initially appear disappointing. For example, small-gauge transconjunctival vitrectomy offered clear advantages to conventional methods for patient comfort and rapidity of visual recovery, but there were also significant concerns of increased rates of endophthalmitis following 25-gauge surgery.5 These red flags led to reappraisal of procedural steps, modification of techniques, attention to case selection, and additional large-scale studies. Subsequently, more recent studies suggest an incidence of endophthalmitis consistent with conventional 20-gauge studies.6

Networking pays off. One physician will rarely have a sufficiently large or comprehensive experience. Developing relationships with colleagues around the country and the world fosters exchange of information and adds to the collective experience of what does and doesn't work. Sharing results or creation of a registry can identify positive or negative trends and determine sample size required to answer the key questions with statistical validity.

Honesty is the best policy. Ultimately, we need to be honest with ourselves and with our patients. We need to know that we are offering something new not to be the first ones in town to do so, not to be able to present it at a meeting, and not for extra reimbursement, but because our critical analysis and clinical knowledge tell us it is a reasonable option. A candid discussion with patients about their desires and expectations will clarify the appropriateness of a new treatment. Further, an honest appraisal of the natural history of their condition, the realistic goals of treatment, and the reasonable odds of achieving that goal will help patients to decide whether they desire to proceed. Just as everyone looks at the half-full glass differently, patients will respond differently to a procedure with a 50% chance of improving visual acuity by two lines.

Caveat emptor. In addition to the scientific, technical, and ethical aspects of adopting and endorsing a new treatment, one must be cognizant of potential financial and medicolegal aspects. With the explosion of health insurance plans, and the relative slowness by insurance carriers to approve new treatments and indications, patients may be caught in the middle of a costly charge that their carrier determined to be investigational, unsupported, or unnecessary. Informed consent for any new treatment should include a thorough discussion of clinical indication, rationale, known and unknown risks, and acknowledgement of any off-label uses.

Ongoing advances in basic science and biotechnology, coupled with the innate creativity of retinal physicians, will continue to generate innovative treatments for patients with retinal diseases. Whether it is bevacizumab monotherapy for ROP or quintuple therapy for AMD, we are in the enviable position of being able to explore new therapeutic options. While we must continue to greet these new treatments with open minds, it is crucial that we rely on objectivity, available evidence, and sound scientific thinking to determine whether, when, and how we adopt them. RP

REFERENCES

  1. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447-1449.
  2. Sackett DL, Rosenberg WMC, Muir Gray JA, et al. Evidence based medicine: what it is and what it isn't. BMJ. 1996;312:71-72.
  3. Johnson RN, Gass JD. Idiopathic macular holes. Observations, stages of formation, and implications for surgical intervention. Ophthalmology. 1988;95):917-924.
  4. Grossniklaus HE, Gass JD. Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. Am J Ophthalmol. 1998;126:59-69.
  5. Kunimoto DY, Kaiser RS, et al. Incidence of endophthalmitis after 20- and 25-gauge vitrectomy. Ophthalmology. 2007;114:2133-2137.
  6. Shimada H, Nakashizuka H, Hattori T, et al. Incidence of endophthalmitis after 20- and 25-gauge vitrectomy causes and prevention. Ophthalmology. 2008;115:2215-2220.


Retinal Physician, Issue: July 2009