Looking Back on an Innovative Year in Ophthalmology
Ronald C. Gentile, MD; Tal Raviv, MD; Joseph F. Panarelli, MD; Richard B. Rosen, MD
Seven Major Advances
In 2014, ophthalmology continued to offer exciting new challenges and stimulate its subspecialists. Not only have advances been made in medical and surgical treatments for blinding eye diseases, but the field has also seen improvements in noninvasive ocular imaging. This year also marked the introduction of big data.
Although some of these new technologies may not have originated this year, their increased acceptance and use over the past 12 months has undoubtedly shaped how ophthalmologists practice now, and will continue to do so in the future. And while it’s impossible to mention every practice-changing event or trend that occurred this year, we have come up with seven that we feel offer as comprehensive a view as possible, with major advances noted across multiple subspecialties.
Enhancing Cataract Surgery
Cataract surgery, considered one the most successful and cost-effective surgical procedures in the world, has made continued advances and improvements. With the increasing popularity of advanced technology intraocular lenses (IOLs), such as multifocal and torics (astigmatism-correcting), cataract surgeons continue to refine the precision of the procedure to maximize visual and refractive outcomes. Recently, two new technologies—femtosecond laser-assisted cataract surgery and intraoperative aberrometry—have emerged that aid these efforts and help cataract surgeons get the most out of premium IOLs.
Despite some controversy, femtosecond laser-assisted cataract surgery appears to represent a paradigm shift for this procedure. The laser is highly focused and creates a plasma of free electrons and ionized molecules that rapidly expand and collapse, cutting tissue at the explosion site with microcavitation bubbles, very precisely and without thermal damage.
Having been used for a decade in creating corneal flaps for laser-assisted in situ keratomileusis (LASIK) surgery, femtosecond lasers have now been adapted to cataract surgery. There are currently four lasers approved by the US Food and Drug Administration (FDA), for precise corneal incisions, corneal arcuates, capsulotomy, and cataract lens fragmentation. Even though this technology may add to the length and cost of surgery, advocates feel it represents the future of this procedure, given its possibility for significantly lowering complication rates (ie, endophthalmitis, dropped nuclei, vitreous loss, posterior capsular opacification) and further improving already successful outcomes with advanced-technology IOLs.
Intraoperative aberrometry is another evolving technology that is being used with increasing frequency to enhance refractive results with IOLs. As patients’ visual expectations after cataract surgery have increased, aberrometry has helped to better achieve the desired refractive endpoint. By taking real-time intraoperative measurements during cataract extraction, aberrometry aids in reducing residual refractive error postoperatively. This is particularly helpful with advanced technology lenses and in post-LASIK surgery eyes.
Intraoperative aberrometry is performed through an aphakic intraoperative refraction (and, in some cases, a postimplantation reading) that allows the surgeon to modify the IOL power or type, measure total corneal astigmatism for toric IOL selection and real-time alignment, and customize arcuate corneal incisions if needed.
Both femtosecond laser-assisted cataract surgery and intraoperative aberrometry, along with other advances in IOLs, elevate the field of refractive cataract surgery, where complication-free surgery is sought for the patient along with a predictable, lifestyle-enhancing, refractive outcome.
The Dawn of Big Data
The Intelligent Research in Sight (IRIS) Registry is the nation’s first comprehensive eye disease clinical registry. It was developed by the American Academy of Ophthalmology and went live in March 2014. The registry has exceeded expectations, with early adoption by 1000 physicians, and it continues to grow. The IRIS Registry was fashioned after similar registries from the American College of Cardiology and the Society of Thoracic Surgeons.
The registry was designed by ophthalmologists for ophthalmologists and will become the model for other medical and surgical specialties to follow in the future. The hope is that it remains within ophthalmology’s control, as opposed to the criticized and widely misinterpreted ophthalmologic physician data from Medicare beneficiaries released by the Department of Health and Human Services in April 2014.
The IRIS Registry is predicted to become “big data,” a term used for any collection of large and complex data sets whose interpretation requires advanced processing applications. It is able to combine patient data from about 30 different electronic health record systems, which can then be followed longitudinally and analyzed for outcomes to a variety of interventions. This could include new treatments in macular degeneration, diabetic retinopathy, retinal detachment, cataracts, and glaucoma.
Besides potential long-term research benefits, the registry is expected to ultimately improve patient care by providing ophthalmologists and ophthalmology practices with critical practice information, such as:
• Easy-to-interpret benchmark reports to validate their quality of care and identify opportunities for improvement;
• Measurement solutions to help enhance quality and practice efficiently, in addition to aiding in participation in quality reporting and incentive programs; and
• Opportunities for sharing quality improvement strategies and broadening professional networks.
Change is inevitable, and although some fear that big data may fall into the wrong hands or otherwise be manipulated, having physicians initiate the process is a great start. Rules on who will have access to the data and what can be done with them in perpetuity need to be ensured. As long as the registry remains aligned with the standards that ophthalmologists recognize as being the best for patients, it should help advance care and achieve better outcomes.
New Diabetic Macular Edema Treatments
This year witnessed an explosion of treatment options for diabetic macular edema (DME). The FDA approved three new intravitreal pharmaceuticals for the treatment of DME.
Aflibercept (approved July 2014) is an anti-vascular endothelial growth factor (VEGF) molecule made up of a soluble VEGF receptor fusion protein that binds to all forms of VEGF-A and related placental growth factor. The dexamethasone implant (approved June 2014) contains 0.7 mg of dexamethasone in the form of a sustained-release biodegradable steroid implant that can last from 1 to 3 months. It is injected using a single-use applicator via a 22-gauge needle with a shelved injection technique. Fluocinolone acetonide implant (approved September 2014) contains 0.19 mg of fluocinolone acetonide in an injectable, nonerodible, corticosteroid implant designed to release submicrogram levels of drug for 36 months. It is injected using an applicator via a 25-gauge needle.
These three drugs were added to the existing armamentarium alongside the intravitreal pharmaceuticals ranibizumab (approved August 2012) and bevacizumab, the latter of which has been used off-label for almost a decade.
In addition to these five intravitreal pharmaceuticals, laser treatments for DME remain an important tool for stabilization. Just as intravitreal pharmaceuticals have proliferated, so too have the types of lasers and techniques used for administering them in DME.
Lasers have had a significant evolution in this area, and barely resemble the focal laser treatment strategies performed during the landmark Early Treatment Diabetic Retinopathy Study (ETDRS) study of the 1980s. Although standard laser treatments for DME have been shown in certain studies to have less favorable outcomes than pure intravitreal pharmacotherapy strategies, they still have significant practical value.
Newer techniques and advances in laser technology are still being developed and have become more popular in an attempt to decrease intravitreal treatment burdens. Subvisible threshold laser treatments to the retina and retinal pigment epithelium using various minimal dosing strategies, such as micropulsing, “endpoint management,” or computer-assisted navigated laser, appear to reduce the photothermal damaging effect while maintaining efficacy.
Retinal Prosthesis for the Blind
In the past, patients who were blind from retinitis pigmentosa or other hereditary photoreceptor diseases had very few options. The Argus® II Retinal Prosthesis System (Second Sight Medical Products Inc.; Sylmar, California) is the first of the next-generation solutions to this problem. After approval by the FDA in 2013, the first nonstudy device was implanted in the United States in January 2014.
The retinal prosthesis is 3 × 5 mm and is installed surgically onto the surface of the retina, where it acts to replace the function of the degenerated photoreceptor cells. The current-generation implant contains 60 electrodes that stimulate the retina with electrical impulses created by a video processing device. That device transforms images from the video camera mounted in a pair of eyeglasses into electronic information that is wirelessly transmitted to the retinal prosthesis.
This implant, also referred to as a “bionic eye,” has been implanted in approximately a dozen patients in the United States, and its use is expected to increase as patient experiences are shared and reimbursement solutions become standardized.
Noninvasive Retinal Imaging
Optical coherence tomography (OCT) has fundamentally altered the way in which ophthalmologists approach the eye, and it promises to continue to deliver better anatomical information and lead the way to functional imaging.
This became immediately evident with the recent introduction of OCT angiographic images produced without injection of extraneous dye. OCT is able to reveal detailed images of large retinal vessels and capillary networks in seconds using a strategy called “motion contrast,” as opposed to the minutes required in conventional fluorescein angiography. These images are uniquely three-dimensional and allow isolated study of individual capillary beds at different depths of the retina.
Although concerns have been raised about loss of the ability to image leakage (owing to the short recording interval), the need to recognize motion artifacts, and the small fields of view, new strategies are being developed to compensate for these limitations. OCT angiography will greatly expand upon the clinician’s ability to noninvasively recognize the subtle progressive vascular changes in diabetic patients that precede macular decompensation and edema.
Adaptive optics is an imaging technology that offers 10 times better resolution than the current generation of clinical systems. Although it is still in the early stages of commercial availability, its use promises to propel retinal imaging to the next level of detail, providing images of individual photoreceptor cells and microvascular structures, including capillaries and microaneurysms.
Clinical insights using these noninvasive imaging tools have the potential to radically expand the understanding of ocular diseases and treatment responses.
Refining Glaucoma Surgery
Although the exact definition of what constitutes microinvasive glaucoma surgery (MIGS) will vary, it has been defined as glaucoma surgery that lowers intraocular pressure by improving the outflow of aqueous humor with limited surgical manipulation of the conjunctiva or sclera. Most are ab interno procedures performed through a small corneal incision. MIGS is best suited for the treatment of mild to moderate glaucoma rather than more advanced disease, and it is characterized as having a favorable safety profile.
The popularity of MIGS proliferated in 2014 for a variety of reasons[17,18]:
• Less hypotony and associated complications compared with traditional glaucoma surgeries;
• Ability to be performed by a comprehensive ophthalmologist without glaucoma training;
• Can be performed in combination with cataract surgery; and
• Does not preclude future traditional glaucoma surgery (ie, trabeculectomy or tube shunt surgery).
As with any new procedure, there is a learning curve that must be overcome when first implementing these devices. The devices that are generally accepted as belonging to the MIGS family are Trabectome® (NeoMedix; Tustin, California), iStent® (Glaukos; Laguna Hills, California), XEN Gel Stent (AqueSys; Irvine, California), Hydrus™ intracanalicular implant (Ivantis; Irvine, California), and CyPass Micro-Stent® (Transcend Medical; Menlo Park, California). Although some have not yet been approved by the FDA, the Trabectome and the iStent were the first to become available to ophthalmic surgeons in the United States.
There is hope that MIGS will soon be able to bridge the wide gap that exists between medical treatment and filtering surgery for patients with glaucoma.
Gene Therapy for Ocular Diseases
By exploiting the ability of human viruses to enter cells, replacing genes has now become a reality in ophthalmology. A modified virus is used as a vector to transport the wanted gene into the affected cell. For some diseases, this has resulted in substantial breakthrough. Although adenovirus is the most common virus vector used, retrovirus and naked/plasmid DNA are also commonly used.
Approximately 2% of current gene therapy clinical trials are focused on ocular diseases, primarily different types of retinal dystrophies (eg, Leber congenital amaurosis, choroideremia, Stargardt macular degeneration, Usher syndrome type 1B, MERTK mutation-associated retinitis pigmentosa). Other diseases include age-related macular degeneration, Leber hereditary optic neuropathy, corneal scarring, glaucoma, DME, and macular telangiectasia type 2.
Most of the ocular gene transfer studies have not reached phase 3 trials; a notable exception is RPE65 gene therapy for Leber congenital amaurosis. Replacing the RPE65 gene via a subretinal injection using adeno-associated virus vector has had promising results with improved visual and retinal function.
Onward to 2015
In the field of ophthalmology, great strides were made in 2014. The proliferation of new therapies in the various subspecialties has enabled ophthalmologists to continue to improve the quality of life of their patients. As with all new technologies, their true ability to withstand the test of time will depend on the clinical experience within the greater community of ophthalmologists.