Our corneal surgeons, who specialize in corneal transplantation and other conditions, are Dr. Martin, Dr. Rubinfeld, and Dr. Adi.
CORNEAL COLLAGEN CROSS-LINKING
Current results are promising, and the procedure has the potential for expanded indications.
BY WILLIAM B. TRATTLER, MD, AND ROY S. RUBINFELD, MD
Corneal collagen cross-linking with riboflavin is
currently performed internationally for the
treatment of a variety of conditions, including
keratoconus and pellucid marginal degeneration.
Researchers are also studying the procedure’s
potential to treat conditions ranging from infectious
corneal ulcers that will not heal to painful
pseudophakic bullous keratopathy. With
cross-linking expected to be approved and
used frequently in the United States, now
is a prime time for clinicians to learn more
about its history, results to date, and
potential future applications. This article
also shares some tips for success.
BACKGROUND
Eberhard Spoerl, PhD, and Theo Seiler, MD, developed the cross-linking procedure in the late 1990s.¹,² The surgeon instills riboflavin (a B vitamin) drops on the cornea after removing the epithelium. Once saturated with riboflavin, the cornea undergoes irradiation with ultraviolet (UV) A light for about 30 minutes (Figure 1). This treatment stiffens abnormally weak corneas, primarily in the anterior 200 to 300 μm, by creating strong bonds (or cross-links) between corneal collagen fibers.³ These bonds function much like the rungs that make a ladder structurally stronger and more rigid. Clinical research has shown that cross-linking not only stops the progression of keratoconus, but it also induces flattening of the cornea and visual improvement.³
TIPS
Preoperative Evaluation During the preoperative assessment, it is important to determine whether a patient with keratoconus is an appropriate candidate for cross-linking. At the slit lamp, the cornea should be clear or at least not severely scarred. The clinician performs pachymetry to ensure that the cornea is sufficiently thick for treatment. After the epithelium’s removal, the corneal thickness should be at least 400 μm. The instillation of hypotonic riboflavin drops can temporarily swell thinner corneas to make cross-linking safe. Studies have shown that the first 300 μm of corneal tissue fully absorb the wavelength of UVA light used in cross-linking (approximately 370 nm), so the minimal amount of UV light that penetrates deeper is well within safe levels.³
Corneal topography and Scheimpflug photography or other advanced imaging allow ophthalmologists to determine the steepness of the cornea. Measurements greater than 60.00 D indicate that the cornea may not flatten enough to make cross-linking worthwhile. Other considerations include a history of corneal herpes simplex virus, which UV exposure may reactivate. Any preexisting dry eye disease requires preoperative treatment, because the condition can delay epithelial healing.
In general, after a complete examination, patients with keratoconus can be advised on whether or not cross-linking has the potential to improve their corneal condition.
Surgery
Cross-linking is a straightforward procedure. After the instillation of topical anesthetic drops and the placement of a lid speculum, the surgeon manually removes the epithelium with a hockey-stick spatula. Some ophthalmologists use dilute alcohol to facilitate epithelial removal. The surgeon then removes the lid speculum, and an assistant instills liquid riboflavin in the eye (one drop every 2 minutes for 30 minutes). After this step is complete, the ophthalmologist performs a slit-lamp examination, which should reveal flare in the anterior chamber of the eye. This finding suggests that the riboflavin has saturated the cornea and the eye is ready for UV light treatment.
After placement of the lid speculum, the patient is positioned under the UV lamp, and the UV beam is centered on the cornea. During the next 30 minutes, an assistant places a drop of riboflavin solution on the eye every 2 minutes while the UV light remains centered on the cornea.
Upon the treatment’s completion, the surgeon places a bandage contact lens and prescribes topical antibiotic and anti-inflammatory drops. At this stage, there are a lot of similarities to excimer laser surface ablation procedures such as PRK. The surgeon therefore selects a topical antibiotic that can reduce the risk of infection and topical anti-inflammatory medications to decrease pain while avoiding delays in epithelial healing.
Postoperative Course
The patient should return 4 to 6 days after the procedure for removal of the bandage contact lens. He or she is instructed to continue the topical antibiotic drop for 7 to 10 days or until no epithelial defect remains. The patient continues using topical steroids for 2 to 4 weeks postoperatively.
CLINICAL RESULTS
In numerous European studies of the safety and efficacy of cross-linking for progressive keratoconus, the corneal shape has typically stabilized and is no longer becoming steeper by 3 months postoperatively. By 6 months, the cornea has become flatter (by as much as 6.00 D or more), and subjects’ BCVA has improved in many cases.³ These improvements in corneal shape and changes in vision appear to continue for more than 6 years.³ After cross-linking, corneal thickness decreases as the tissue becomes stronger and more compact. This thinning becomes evident at 1 month and persists long term.³
In the United States, R. Doyle Stulting, MD, PhD, initiated a multicenter study in 2007. The preliminary results showed a stabilization of the corneal shape at 3 months and flattening by 6 months after treatment. In contrast, control eyes (which did not undergo cross-linking) continued to experience progressive keratoconus and to lose vision during this time period.4
Because cross-linking strengthens the cornea, patients may become eligible for laser vision correction. Preliminary results with PRK for these individuals have been favorable, with a significant improvement in UCVA and BCVA.4
FUTURE INDICATIONS
In addition to therapy for keratoconus and post-LASIK ectasia, corneal collagen cross-linking with riboflavin may play a role in the treatment of corneal infections. A recent in vitro study revealed that both riboflavin alone and UV exposure alone were inadequate at killing Staphylococcus aureus, methicillin-resistant S aureus, and Pseudomonas aeruginosa. The combined application of riboflavin and UV exposure, however, eliminated these organisms.5 In the future, cross-linking may serve as an adjunctive treatment for challenging corneal infections.
Research has also focused on the treatment of pseudophakic corneal edema in patients who may not be good candidates for corneal transplantation. Early studies have shown that cross-linking can induce a reduction in cor- 54 I CATARACT & REFRACTIVE SURGERY TODAY I SEPTEMBER 2009 COVER STORY “During the preoperative assessment, it is important to determine whether a patient with keratoconus is an appropriate candidate for cross-linking." neal thickness. Investigators studied 10 patients with an average preoperative corneal thickness of 840 μm. On average, 9 months after treatment, the corneal tissue had thinned by 125 μm, and eyes had gained one line of BCVA.4 Cross-linking may prove more effective than corneal micropuncture at relieving the discomfort of patients with corneal edema.6
At present, cross-linking is an exciting procedure performed internationally that has the potential to help patients with a variety of clinical conditions. Surgeons are working hard to make this therapy available to patients in the United States.
Roy S. Rubinfeld, MD, is a clinical associate professor at Georgetown University Medical Center and on staff at The Washington Hospital Center in Washington, DC. He is in private practice with Washington Eye Physicians & Surgeons in Chevy Chase, Maryland. Dr. Rubinfeld may be reached at (301) 654-5290; rubinkr1@aol.com.
William B. Trattler, MD, is the director of cornea at the Center for Excellence in Eye Care in Miami. Dr. Trattler may be reached at (305) 598-2020; wtrattler@earthlink.net.
1. Spörl E, Huhle M, Kasper M, Seiler T. Increased rigidity of the cornea caused by intrastromal cross-linking [in German]. Ophthalmologe. 1997;94(12):902-906.
2. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66:97-103.
3. Kohlhaas M, Spoerl E, Schilde T, et al. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006;32:279-283.
4. Stulting RD. Update on riboflavin-UV crosslinking. Paper presented at: The ASCRS Symposium on Cataract, IOL and Refractive Surgery; April 6, 2009; San Francisco, CA.
5. Greebel GJ, Schrier A, Attia H, et al. In vitro antimicrobial efficacy of riboflavin and ultraviolet light on Staph aureus, methicillin resistant Staph aureus (MRSA) and Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci. 2009;50:e-abstract 5117.
6. Rubinfeld RS, Laibson PR, Cohen EJ, et al. Anterior stromal puncture for recurrent erosion: further experience and new instrumentation. Ophthalmic Surg. 1990;21(5):318-326.
THE CORNEAL SURGERY PATIENT
Most people who have been told they might need a corneal transplant are understandably uncertain and concerned. They don't always know what to expect in terms of success rates, discomfort, and physical activity after the procedure. Most patients have mild discomfort for the first few days after surgery, and they usually return to work after about three to four days.
What is Corneal Transplantation?
Corneal transplantation (also called penetrating or perforating keratoplasty) is by far the most commonly performed and most successful transplant procedure. Unlike other forms of transplantation, patients generally do not require any anti-rejection pills or intravenous medications, and in most cases it is uncommon for rejection to interfere with the eventual success of corneal transplants. The cornea – the “clear window” in front of the eye – usually has no blood vessels in it, so the body's immune system is unaware of the surgery. For most patients, rejection rarely causes failure of the transplant.
Click here to read about the newest advance in corneal transplantation-DSAEK
What Conditions May Lead to Corneal Transplantation?
Common corneal conditions that require transplantation surgery include keratoconus, corneal edema, and corneal dystrophies. Corneal transplant surgery has evolved into a highly specialized procedure, best performed by surgeons who are corneal fellowship trained. We usually perform our transplant surgery in our state-of-the-art Eye Surgery Center, a freestanding ambulatory surgery center that specializes in eye surgery.
Discomfort After Surgery
Most patients experience a foreign body sensation (as if something were in their eye) for several days after surgery. Often, the eye aches and itches and bright lights may be temporarily uncomfortable. This discomfort improves over the course of several days. At no point after the first day or two should you experience severe pain. If you experience pain that is not relieved by Tylenol, you should call the office and ask to speak with your surgeon. Most patients can return to their usual routines within several days after surgery. You may even watch TV soon after your surgery.
Post-surgery Restrictions
The most important thing to remember is to not let anything strike your eye. You will need to wear the eye shield at night to avoid inadvertently rubbing your eye while you are sleeping. Your surgeon will tell you when to discontinue the use of this shield. Avoid lifting objects heavier than 30 pounds within the first few weeks after surgery. Also, do not bend over with your head below your waist until your doctor says you can do so. If necessary, you may take a laxative to avoid straining. If you exercise regularly, check with your surgeon regarding what exercises are acceptable at different points in your recovery. The most important precautions you can take to protect your eye involve wearing the shield at night and glasses (of any sort) during the day to avoid a blow to the eye, which could jeopardize the success of your surgery.
Leave the patch and shield on after surgery until your surgeon removes them on your first post-op visit. A “black eye” after surgery with a black and blue appearance to your lids is normal, and this will resolve over a few weeks. Mild lid swelling is also normal. A little bloody discoloration of your tears for a week or so is not cause for concern. The eye is often quite red after surgery for a few weeks. A clean, warm, wet washcloth can be used to gently clean crust from the lids.
Your First Post-Op Visit
It is essential that you return for your scheduled appointments after surgery. At the first post-operative visit, your surgeon will tell you how to use your eye medications after surgery. Please bring with you the package of eye medicines that you received after your surgery was completed. If you use medicines in your other eye, continue to use the same medicines (without change) in that eye. You should use the following medications in your operated eye (until your surgeon changes your instructions).
Please don't hesitate to ask either the ophthalmic technician or your physician if you have any questions whatsoever. Please feel free to call with questions. We would much prefer to determine that nothing is wrong, than for you to experience a potential problem and worry or ignore it, hoping it will resolve by itself.
Expected Vision After Surgery
Contrary to popular opinion, your vision will not improve immediately after surgery. In fact, your vision may be worse after surgery than it was before surgery. For the first few weeks or months following surgery, you will likely experience daily fluctuations in your vision. However, if your vision improves over the course of several weeks and then suddenly dramatically decreases, this may be cause for concern.
At about three months after a corneal transplant, your surgeon will consider changing your glasses to allow better vision in that eye. Most patients get their best vision about one year after the transplant. Also, increasing redness and light sensitivity is a possible sign of a problem, as is seeing bright flashing lights, a “curtain” across your vision, or a large shower of floaters. Some floaters after surgery, however, are to be expected.
A Success Story
One of our many corneal transplant patients, Howard Beiles, sent us this picture from the top of Mt. Kilimanjaro in Tanzania. His procedure by one of our Washington Eye surgeons allowed him to see the beauties of the surrounding area from nearly 20,000 feet (if you look closely, the flag he is holding bears the surgeon's name). Patients like Mr. Beiles, with the diagnosis of keratoconus or endothelial dystrophy, have the highest success rates after their corneal transplants.
DSAEK
DSAEK (DESCEMET STRIPPING ENDOTHELIAL KERATOPLASTY)
Sutureless Corneal Endothelial Transplant
For the treatment of corneal swelling, DSAEK is a way of performing a safer corneal transplant than traditional PENETRATING KERATOPLASTY (PKP). Only the damaged endothelial layer is replaced, leaving the remainder of the cornea undisturbed. In a traditional transplant of the cornea a full thickness incision is made, creating a circular opening in the front of the eye that requires many sutures to secure the transplant. In DSAEK the new cornea is inserted through a small incision that requires one suture for closure; the graft is then supported by an air bubble until it stabilizes.
Because the new transplant does not require sutures, there is less induced irregularity or change in the curvature of the recipient cornea (astigmatism). This translates into faster rehabilitation of vision, fewer postoperative physical restrictions and a stronger eye after surgery which is less susceptible to injury from trauma. The surgical incision is smaller and does not greatly alter the eye’s integrity. There is also less concern about sutures breaking and causing infections.
WHAT IS CORNEAL SWELLING?
Swelling of the cornea can result from premature aging of the cornea’s inner lining (Fuch’s Endothelial Dystrophy) which is a hereditary condition, or as a result of loss of these inner cells (endothelium) due to trauma, including previous eye surgery. This is where DSAEK can be most helpful in restoring vision. DSAEK does not work in scarred or irregularly shaped corneas.
DONOR CORNEAS------ WHERE DO THEY COME FROM?
Loosing a loved one is undoubtedly devastating; a donated cornea from a healthy eye is a gift of sight that lives on. “Donor” refers to the person providing the cornea; “recipient” is the person receiving the cornea. There is no need to match the tissue, eye color or gender for corneal transplants. We usually do attempt to match the general age, especially when operating on a child or young adult, as these individuals have much longer life expectancy. It is a common misconception that, when donating the corneas, the body will be disfigured. This is not true. Only a portion of the cornea the size of a dime is donated.
HOW IS DSAEK DONE?
The surgery is performed under mild sedation. Numbing medication is also used so there is little or no discomfort. Using sophisticated instrumentation adapted from LASIK procedures, the donor cornea is prepared and placed in the recipient’s eye. This new graft is then supported by an air bubble that presses against the recipient’s cornea while the patient is comfortably lying on their back. The bubble takes the place of sutures and is only necessary for a short period of time after completion of the surgery.
BEFORE YOUR SURGERY:
Your surgeon will meet with you in our office and examine you before deciding on surgery. Testing and measurements will be performed at the time of your appointment. Any questions will be answered and the informed consent (giving permission to your surgeon to perform the surgery) will be explained and signed. Our business office will review the cost of the procedure (most insurances and Medicare cover much of the cost). Your surgeon and the staff at Washington Eye Physicians & Surgeons will explain post-operative care and will address any other questions you might have about your outpatient surgery, DSAEK. You will be asked to use antibiotics and other eye drops prior to your surgery, and it is very important not to eat anything after midnight on the night before your procedure.
POST – OPERATIVE CARE:
Your surgeon will check your healing on the day after surgery. Your vision is not expected to be improved immediately at this visit; in fact, it is usually worse on your first post-op day.
There is usually no pain after surgery although some light sensitivity and scratchiness is common. Visual recovery varies depending on the severity of your corneal cloudiness prior to surgery. Most patients notice improvement in their vision during the first two weeks after surgery with continued improvement during the next four to six weeks. This is faster than the many months and often years of rehabilitation needed after a traditional transplant.
Post-operative visits are scheduled at one day, one week, and one month after the procedure, then monthly depending on the patient’s progress.
- You will usually be able to resume most activities 2 days after surgery.
- Eye makeup is allowed at 1 week and swimming at 4 weeks after surgery.
- Exercise such as treadmill, or walking are permitted at 1 week.
- Jogging or weight lifting should be avoided for 3 to 4 weeks.
You will likely have a change in your eye glass prescription at some point after the surgery.
ADVANTAGES OF DSAEK:
- Visual recovery is significantly faster.
- The eye is less susceptible to injury after surgery.
- There is usually less astigmatism and less change in your eyeglass prescription.
- Suture related problems are reduced.
- There are fewer restrictions on physical activity after the surgery.
