Cohen EJ. Cornea and External Disease in the New Millennium. Arch Ophthalmol. 2000;118(7):979–981. doi:10-1001/pubs.Ophthalmol.-ISSN-0003-9950-118-7-esa90017
It is a challenge to speculate about the changes and advances related to the cornea and external disease as we enter the new millennium. The remarkable advances in refractive surgery during just the past decade have made it a huge field of ophthalmology, which is beyond the scope of this article. Subjects to consider include corneal transplantation, infections, dry eyes and blepharitis, ocular surface reconstruction, corneal imaging, contact lenses, and eye banking. Speculation regarding the future of any field of ophthalmology must be made in the context of larger trends regarding health care policies in the United States, as the current emphasis on control of medical costs may have a negative impact on progress through deleterious effects on medical training and research.
Although corneal transplantation is currently frequently performed with a high success rate, there are issues that leave room for progress. Patients require meticulous long-term care following corneal transplantation to obtain optimal results. Success remains limited in patients with corneal neovascularization, severe ocular surface disease, and congenital corneal opacities. Topical corticosteroids are the standard treatment for the prevention and treatment of allograft rejection episodes, but their adverse effects, including steroid-induced glaucoma, cataract formation, increased risk of infection, and impaired wound healing, are well known. The development of equally effective and safer topical medications is under current investigation. Generally, the newer topical corticosteroids that have become available seem to be safer but not as effective as standard prednisolone or dexamethasone. Use of topical cyclosporine has had mixed results, but seems to have a steroid-sparing effect in patients with steroid-related complications and has considerably improved the prognosis of penetrating keratoplasty for congenital corneal opacities. Low-dose topical cyclosporine will probably become commercially available in the near future. Hopefully, safer and more effective topical antirejection agents will become available in the years to come.
Astigmatism remains a problem for visual rehabilitation in patients with clear corneal transplants. Prevention of astigmatism may be achieved in the future by improvements in the preparation of the host and donor corneas, such as laser-guided tissue removal, development of well-tolerated permanent sutures or adhesives, and ways to enhance wound healing. Advances in contact lenses and refractive surgery may also improve the management of postoperative astigmatism.
It is also reasonable to speculate about advances that could obviate the need for corneal transplantation. In recent years, excimer laser phototherapeutic keratoplasty has become the initial approach for the treatment of superficial stromal corneal dystrophies, including Thiele-Benke, lattice, and granular dystrophies. Although gene therapy has not made the advances predicted and has faced recent devastating complications, it is conceivable that these corneal dystrophies may be amenable to topical gene therapy. These diseases are superficial in their early stages, and current information suggests that they represent different abnormalities of the same gene. Similar advances in the understanding of the biochemical and genetic basis for keratoconus in the future could translate into effective topical therapy that could prevent disease progression. One can imagine the day when corneal edema would no longer be the most common indication for corneal transplantation due to advances in the safety of cataract surgery and perhaps the development of topical agents, which could preserve endothelial function, or the ability to transplant endothelial cells only. The recent development of artificial corneas is promising for evaluating drug safety and efficacy but is unlikely to be useful for corneal transplantation in the foreseeable future. These speculations may be far-fetched, but when one considers the amazing progression in the past half century, it is possible some may become reality.
Turning to corneal and conjunctival infections, the future holds the possibility for important improvements, but there are legitimate concerns about the potential for worsening. The rise of infections caused by drug-resistant organisms has to date been a greater problem for medicine in general than in ophthalmology, but this could change in the future. New drugs are being developed for vancomycin-resistant organisms. There should be more widespread support among the medical community, including ophthalmology, for more restrictive use of antimicrobial agents to try to delay the emergence of drug resistance. As the population ages and life expectancy increases for patients with various long-term diseases, it is likely that the number of immunocompromised patients with reduced resistance to infection will also rise.
A more optimistic view is that infections may be reduced. The availability of a vaccine against chicken pox in recent years may translate into fewer patients with herpes zoster ophthalmicus in the future. Progress has been made with currently available systemic antivirals to reduce by 50% recurrent herpes simplex keratitis. In the future, more effective drugs may be developed that eliminate latent infection and subsequent recurrent disease, or better, a vaccine may prevent herpes simplex virus infections. Topical cidofovir is currently being studied for treatment of adenoviral conjunctivitis. The use of ivermectin holds the promise of eradicating onchocerciasis, or river blindness, in the next few years. Azithromycin is effective when given as a single oral dose against trachoma. This common cause of blindness in the developing world may be controlled by repeated treatment in endemic areas in the not so distant future. Regarding the improved diagnosis of various infections, perhaps confocal biomicroscopy will become as routine as slitlamp biomicroscopy, and the findings will be as readily understood as the results of smears and cultures. Further development and routine usage of polymerase chain reaction tests for corneal and conjunctival specimens may facilitate specific diagnosis of infections.
Dry eyes and blepharitis are common diseases that cause long-term ocular discomfort and, in some circumstances, potentially blinding corneal ulcers and perforations. Currently, there is new information regarding the inflammatory and hormonal nature of dry eyes and the possibility that topical immunomodulatory agents such as cyclosporine or hormones may be beneficial. Although there is cause for optimism, caution is in order since new agents bring the possibility of new complications, as in the case of topical nonsteroidal anti-inflammatory agents that have recently been linked with serious corneal complications, including corneal melting and perforation. Regarding blepharitis and rosacea, topical agents such as metronidazole are being studied, which may reduce or eliminate the need for systemic tetracycline administration in moderate and severe cases. Whenever possible, the search for topical ocular therapy is preferable to systemic treatment with the potential for adverse effects.
Ocular reconstruction for patients with severe ocular surface disease such as aniridia, chemical burns, and ocular cicatricial pemphigoid, using limbal cell transplants and amniotic membrane has made enormous advances in recent years. There is now hope for patients who in the past failed with all other approaches. Long-term systemic immunosuppression is necessary for these patients and success remains limited in patients with Stevens-Johnson syndrome. Continued progress will hopefully occur regarding the prevention of rejection with topical agents. Improvements in permanent keratoprostheses may increase their use beyond patients with severe bilateral chemical burns and cicatrizing diseases. Prevention of chemical eye injuries by means of eye protection in occupations that put employees at risk for exposure to hazardous materials and efforts to decrease violence in our society could reduce the burden of severe chemical burns.
Corneal imaging in the past decade has moved from a research technique to an indispensable clinical test for the diagnosis and evaluation of patients with irregular astigmatism due to corneal disease or following refractive surgery. The technology is actively evolving, and the widely used placido-based systems may be replaced by other, more accurate methods. A slit-beam system now can evaluate posterior corneal curvature, which may be a method to detect early corneal ectasia, especially after refractive surgery. Recently, wave-front technology has been used to develop imaging systems that detect optical aberrations and can be used directly to guide refractive surgical procedures.
Regarding contact lenses, the recent availability of daily disposable lenses holds the hope for improved safety. Perhaps improved contact lens materials will reduce or eliminate the increased risk of corneal ulcers associated with overnight wear of contact lenses. There is room for improvement in contact lens disinfection, combining simplicity and efficacy against a wide range of organisms, including bacteria, fungi, and acanthamoeba. In the future, gas-permeable lenses may be truly custom fitted using accurate corneal imaging linked to lens manufacturing. The need for gas-permeable lenses may be reduced by other approaches for the prevention and treatment of irregular astigmatism.
Advances in eye banking have greatly improved the availability and quality of donor tissue to the point of eliminating long waiting lists in industrial Western societies. Major cultural changes, however, are needed to improve corneal donation in non-Western societies. Further advances in donor storage media may improve the preservation of the corneal endothelium and epithelium for longer durations and reduce the risk of infection following corneal transplantation. However, refractive surgery may reduce the pool of donors considerably. Studies are planned to evaluate long-term results with the use of healthy older donor tissue to try to improve the potential source of donors.
But how will the current medical climate in the United States affect all these potential advances? Research is necessary for progress. Academic medical centers are critical for medical research and training in the United States. For-profit hospitals and health maintenance organizations are not committed to training and research. Current health care policies have reduced reimbursement to academic medical centers, which also care for many indigent patients. Huge financial losses threaten the viability of many academic medical centers and already negatively affect research and training. The government, through support of the National Institutes of Health, Bethesda, Md, recognizes the importance of medical research. A high priority for the near future is to provide adequate funding to secure the future of research and training at academic medical centers; otherwise, medical progress will not proceed, and the current quality of medical care will diminish. Continued quality clinical training and research is key to a bright future in ophthalmology and medicine in general.
Accepted for publication March 21, 2000.
Corresponding author: Elisabeth J. Cohen, MD, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19105.