COMMENTARY

Cornea and External Disease: Latest Trends in Medical and Surgical Care

American Academy of Ophthalmology 2012

Christopher J. Rapuano, MD

Disclosures

November 20, 2012

Editorial Collaboration

Medscape &

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Thermal Pulsation Therapy for Blepharitis

Hello. I'm Dr. Christopher Rapuano, Chief of the Cornea Service at Wills Eye Institute in Philadelphia. Welcome to Medscape Ophthalmology Insights. This is part of a series of commentaries produced in cooperation between Medscape and Wills Eye Institute. I'm here at the American Academy of Ophthalmology (AAO) meeting in Chicago, and I will be discussing some of the highlights in cornea and external disease from this year's meeting.

I will start with medical treatments. Thermal pulsation therapy for blepharitis -- we all have many patients with chronic blepharitis, and unfortunately some of them are poorly responsive to standard therapies. There is a new US Food and Drug Administration (FDA)-approved treatment for blepharitis.[1] This involves simultaneous heat and compression of the upper and lower eyelids. The idea is that while the eyelids are being heated, the compression actually forces a cleaning out of the meibomian glands. The treatment takes about 12 minutes, and it can be done 1 eye at a time or both eyes at once. I had this treatment done on myself. It's fairly comfortable -- certainly not uncomfortable -- and may help some patients with chronic blepharitis. Although few studies are available in the literature yet, those of us who see many of these chronic sufferers are quite hopeful that this will be a nice addition to our treatment of these patients.

Medical or Surgical Treatment for Ocular Surface Squamous Neoplasia?

The second medical therapy is treatment for ocular surface squamous neoplasia, so squamous cell carcinomas or carcinoma-in-situ of the conjunctiva and cornea. There was a point-counterpoint debate[2,3] at Cornea Subspecialty Day, which talked about whether surgery or medical therapy as a first-line treatment was the preferred way to manage these patients. The medical therapies included mitomycin C, 5-fluorouracil, and interferon alpha-2B. One of the doctors proposed that surgery was the best initial treatment for these cancers, and a main reason was to obtain a histopathology diagnosis so you knew exactly what you were treating. In addition, when it worked, surgery was a one-time treatment that didn't require expensive medications and ongoing patient cooperation. The opposing side felt that the fact that medical therapies did not involve surgery was an advantage, and there was no damage of the limbal stem cells, which is another good thing.

The bottom line is that, as an initial treatment, surgery provides a diagnosis and is often less expensive in the long term and doesn't require patient compliance. This is very reasonable, although medical therapy can be tried if the diagnosis isn't in question and the patient is not interested in surgery, or if the cancer is very diffuse and you feel that surgery will do too much damage to the limbal stem cells. Even if surgery is performed first, if there are lid margins that are positive on histopathology or if there is postoperative recurrence of the tumor, then topical therapy can be used. Furthermore, if the patient has a very large conjunctival tumor, medical therapy can be used initially to shrink the tumor before surgical excision.

Steroids for Corneal Ulcers

Another treatment that was discussed was steroids for corneal ulcers. This has been controversial in the past. Some people use steroids at the beginning of corneal ulcer therapy, some use them later, and some people feel that they shouldn't be used at all in the treatment of corneal ulcers. A large, 500-patient, randomized trial of steroids in the treatment of corneal ulcers was recently published.[4]These corneal ulcers were all culture-positive for bacteria and they were all treated with intensive moxifloxacin. Prednisolone phosphate 4 times daily was started 48 hours after treatment. They found that the steroids might have helped a little with respect to visual acuity months after the infection, but not statistically significantly so. However, just as important, if not more important, was the finding that the steroid cohort did not have more complications -- perforations, chronic ulcers, or failures of therapy. In the end, steroids can be used, although positive cultures are important and steroids probably shouldn't be used for the first day or two until after the antibiotics have had some effect.

CMV Endotheliitis

Cytomegalovirus (CMV) endotheliitis was another topic. This is not a common diagnosis, and it's not something we think about much at all. However, one of the speakers[5] made a point that we should really suspect this in cases of corneal graft rejection, including penetrating keratoplasties and endothelial keratoplasties. If you have a patient with keratic precipitates (KPs) and an anterior chamber reaction after a corneal transplant, you should suspect rejection. You also need to think about CMV endotheliitis. The speaker made a point of trying to differentiate graft rejection from CMV infection; and findings of heavily pigmented KPs, KPs on the graft and on the host, significant Descemet folds, and no neovascularization pointed more toward CMV endotheliitis. It is not always easy to tell clinically, and an aqueous tap for polymerase chain reaction (PCR) is needed to make a definitive diagnosis. If you make the diagnosis, the treatment is oral valganciclovir for several months. It's unclear when to stop therapy. Some people stop when the anterior chamber reaction is gone, and some people do a repeat PCR and stop only when the PCR is negative. Some people don't stop at all, or they stop the oral medications and use topical antiviral agents for months, if not indefinitely. This treatment is still in evolution, but it's definitely something to think about when you have a patient with graft rejection.

Collagen Crosslinking for Keratoconus

Now I'm going to talk about surgical treatments. Several of these were brought up during the meeting this week. The first is collagen crosslinking for keratoconus.It is becoming well accepted that collagen crosslinking works well to slow down, stop, and even reverse some keratoconus changes. It has been done in Europe, South America, Asia, and around the world for 5-10 years, and it is becoming more popular in the United States with some ongoing FDA trials.

There are several controversies. One is, at what age should this be done? Speakers were unclear as to the exact lower age for this procedure, but the consensus seems to be that as soon as you see evidence of progressive keratoconus, it is reasonable to treat that patient. They talked about patients as young as 10, 12, or 15 years old [undergoing collagen crosslinking]. What about an upper age limit? Again, it is unclear, but somewhere in the age group of 35-50 years old might be a good upper limit because keratoconus doesn't usually progress after that age.

Another controversial point was whether there is a severity of keratoconus at which time it is too severe for patients to be good candidates for collagen crosslinking. No exact numbers were agreed upon, but if the keratoconus is very severe with very high keratometry readings, these patients are probably not great candidates for collagen crosslinking.

Another controversial issue is whether to leave the epithelium on or remove the epithelium before placement of the riboflavin. However, during Cornea Subspecialty Day, Theo Seiler[6] recommended removing the epithelium.

Over the past 5-10 years, these treatments have typically used 30 minutes of ultraviolet treatment. Thirty minutes is a long time for physicians and for patients, so one question is, can you increase the intensity of the ultraviolet treatment and reduce the duration? Dr. Seiler felt that this was a reasonable thing to do, although the optimal intensity and duration are not known. In fact, at the Wills Eye Institute, we are part of an FDA trial using collagen crosslinking and randomizing 3 different intensities and durations of ultraviolet treatment.

DMEK or DSEK?

Perhaps one of the biggest topics of discussion at the meeting this week, as far as cornea surgeons are concerned, is Descemet's membrane endothelial keratoplasty (DMEK). Many cornea surgeons are performing Descemet's stripping endothelial keratoplasty (DSEK), where stroma, Descemet's, and endothelium are transplanted into the patient. With DMEK, only Descemet's and endothelium are placed into the eye.

The advantages of DMEK over DSEK include faster visual recovery, higher chance of 20/20 vision, less refractive shift, and perhaps less rejection. However, as with many new techniques, there are several disadvantages. First of all, it's more difficult to separate Descemet's from the donor cornea, and not infrequently there is wastage of donor tissue when that happens. That certainly should be minimized for many reasons.

Currently there are numerous methods for unfolding the tissue in the eye, and whenever you hear about numerous methods for a certain procedure, you know that there isn't one method that is really ideal. Many surgeons who start DMEK notice that a significantly high percentage of patients need rebubblings a day -- or 3 days or a week -- after surgery, when they need to reinject air into the anterior chamber to reattach the periphery of Descemet's.

To help with DMEK and to make it easier, safer, and more reliable, new procedures have been proposed. One is that the eye banks would supply preprepared tissue so that Descemet's is actually separated from the stroma and then put back down, and when it comes to the surgeon, the risk of tearing Descemet's and wasting the tissue is minimized. Perhaps preloaded tissue may be something that an eye bank could do. There are newer insertion techniques with newer inserters that may be easier, safer, and more reproducible. Furthermore, some surgeons are using a long-acting gas, such as SF6, in the anterior chamber, which may last longer and allow the DMEK to attach better to reduce the number of rebubblings that are required.

I hope you enjoyed listening to some of these highlights from this year's AAO meeting. Thanks for joining us. This is Dr. Christopher Rapuano for Medscape Ophthalmology and Wills Eye Institute.

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