Recent Research in the Treatment of Anterior Segment Eye Disease


Recent Research in the Treatment of Anterior Segment Eye Disease

By Marjorie Jeandervin, OD, MS
March 2000

There have been some astonishing scientific breakthroughs in the last few years. For example, the world was amazed when Dolly the sheep was the first animal cloned, but hold onto your hats. The December issue of Nature reported that human corneas are now being grown in a laboratory at the University of Ottawa. Although the corneas are far from ready for use in transplantation, the laboratory-grown corneas resembled human corneas in gross morphology, transparency and histology. These corneal equivalents also showed wound-healing reactions similar to human corneas when exposed to surfactants. Similar changes in transparency to human and rabbit corneas were also observed in response to chemical injury. Before corneal equivalents may be used in transplantation or as an alternative to animal research in the future, thorough testing of immune responses and the cancerous nature of the cells must be completed.

The Endothelium with CLs

We know that long-term contact lens wear causes changes in the corneal endothelium. But what we don't know is the long-term impact refractive surgery has on the corneal endothelium. Many patients who have refractive surgery are previous long-term contact lens wearers. The fact that we are unsure of the effect of refractive surgery on the endothelium poses an important question about safety.

A group of doctors at the Mayo Clinic Department of Ophthalmology studied the changes in central and peripheral corneal endothelium in a group of long-term contact lens wearers and compared their findings to a group of age- and sex-matched nonwearers. The investigators used wide-field contact specular microscopy to evaluate endothelial cell density and coefficient of variation of cell area. They found that overall cell density was not decreased in the contact lens wearers, but that a mild redistribution of endothelial cells from center to periphery did occur (Fig. 1). The next step in the future is to determine the impact of these changes in endothelial cell distribution on the safety of refractive surgery procedures.

FIG. 1: Endothelial polymegithism.

Breakthroughs in the Treatment of Herpetic Eye Disease

The Herpetic Eye Disease Study (HEDS) is an eight-center prospective study designed to evaluate the effectiveness of various pharmacological combinations for different aspects of herpetic disease. Several trials have been performed to evaluate the treatment options for acute herpetic stromal keratitis, iridocyclitis, epithelial keratitis, iritis and prophylaxis for the prevention of recurrent ocular disease. Probably the most interesting result that has been reported involves the use of oral acyclovir for prophylaxis. Patients with a history of ocular herpetic disease were given 400mg of acyclovir twice daily orally for a period of 12 months. Those patients showed a reduction in the rate of ocular and orofacial disease. It should be noted however, that the prophylactic benefit ended with discontinuation of the drug, and some patients who received the treatment did have recurrences. Future studies will determine whether different dosages will be more effective and whether new drugs, such as valacyclovir and famcyclovir, will produce similar or even better prophylactic results. Other interesting findings from HEDS include the following:

  • Treatment with topical steroids was effective in reducing the persistence or progression of stromal inflammation.
  • Kreatment with topical steroids was also effective in shortening the duration of stromal keratitis.
  • Although the sample size was not adequate to determine statistical significance, oral acyclovir appeared to be beneficial in the treatment of herpetic iridocyclitis.
  • No significant benefit was found when oral acyclovir was used in combination with topical corticosteroids and trifluridine to treat stromal keratitis.
  • Oral acyclovir did not appear beneficial in preventing subsequent stromal keratitis or iritis.

How Do We Typically Fit Keratoconic Lenses?

The Collaborative Longitudinal Evaluation of Keratoconus Study, better known as the CLEK Study, took a look at the community standard of care with regard to the apical fitting relationships of rigid contact lenses in keratoconus patients. To determine the fitting relationships, the base curve of the patients' habitual lenses was compared to the first definite apical clearance lens (FDACL). The FDACL lens represents the flattest lens that still gives an apical clearance fluorescein pattern. Of the 1,209 patients enrolled in the study, 808 habitually wore contact lenses. Of those contact lens wearing patients, 95 eyes were wearing lenses fitted with apical clearance, and 713 eyes were wearing lenses fitted with apical touch. Habitual lenses at least 10.00D flatter than the FDACL were found in 33 patients.

The more severe the disease, the flatter the lenses are typically fitted (Table 1). So why is this an area of concern? Because it has been hypothesized that flat-fitting lenses pose a risk for potential corneal scarring. Future research being conducted by the CLEK Study group will determine whether we need to change our keratoconic fitting habits.

TABLE :  Keratoconic Lens Fitting

Mild (<45.00D)  1.18D flatter
Moderate (45.00 to 52.00D)  2.38D flatter
Severe (>52.00D)   4.01D flatter

What's New in Dry Eye

In last year's review of the literature, I included a review of the pathology of dry eye. This year, I decided to give you a brief update on what's happening in the world of dry eye and contact lenses.

A questionnaire administered to relatively successful full-time contact lens wearers revealed that symptoms of dryness, frequency of blurring and changeable vision are worse in the evening. These patients also reported decreased comfort at the end of the day. The symptoms of dryness were less common when the patients weren't wearing their contact lenses. Were the symptoms bad enough to cause the patients to discontinue lens wear? No.

Despite the symptoms reported, most patients didn't remove their contact lenses. The bottom line: it may be better to schedule patients with dry eye symptoms later in the day.

Diagnoses for Penetrating Keratoplasty

Ever wonder what the leading diagnoses are prior to penetrating keratoplasty? According to a report by a group in Toronto, Canada, as of 1980, pseudophakic bullous keratopathy is the foremost diagnosis (see Table 2). They reviewed the charts of over 6,000 patients who had undergone the surgery between 1964 and 1995. The runners-up were regraft, in second place, followed by keratoconus. Prior to 1980, the leading diagnosis was keratoconus. The surprising fact, at least in my opinion, is the high ranking of regrafts. Eighteen percent of the reported surgeries -- a total of 1,115 cases, were repeated transplants.


TABLE 2: The Top Six Leading Diagnoses for PKP

1) Pseudophakic bullous keratopathy
2) Regraft
3) Keratoconus
4) Fuchs'
5) Trauma
6) Viral

The age distribution of patients undergoing transplant showed a bimodal distribution with peaks in the fourth and eighth decades of life. This represents the age-specific characteristics of diseases such as keratoconus and pseudophakic bullous keratopathy (Fig. 2). The number of penetrating keratoplasties performed has increased over the last three or four decades, and as the availability of donor tissue increases, we will most likely see a steady increase in the future.

FIG. 2: pseudo-phakic bullous keratopathy.

New Complication with High Hyperopic PRK

As a result of the current FDA approvals, and even more that are in the pipeline, refractive surgery is becoming more commonplace for our hyperopic patients. Unfortunately, with this increase in hyperopic refractive surgery cases comes a new roster of surgical complications.

A group of doctors at the Cleveland Clinic Foundation Cole Eye Institute reported on a newly observed complication following hyperopic photorefractive keratectomy (PRK). Case reports of three out of 1,000 consecutive surgical patients who underwent hyperopic PRK revealed central bump-like corneal opacities.

Although the incidence of this newly reported complication is low, it is of concern due to the accompanying loss of spectacle corrected visual acuity. You may be wondering what could be causing these corneal opacities? Suction ring alignment difficulties, multiple optic zone markings and prelaser stromal edema with irregular folds occurred in each case.

Phototherapeutic keratectomy was the treatment performed in each case; however, it was discovered that due to the depth of the opacities, reoperation only temporarily resolved the problem.

Bottled Water and Contact Lenses

Because the microbiologic quality of bottled water is often misconstrued as being superior to that of tap water, patients have been know to use it instead of sterile saline to rinse their contact lenses. The Cullen Eye Institute in Houston tested two different lots from 23 brands of noncarbonated bottled water to determine whether the water has the possibility of contaminating the contact lenses. Viable microorganisms were found in 11 of the 23 brands tested. Gram-negative rods, predominantly Pseudomonads, were the most commonly detected. So although it's refreshing to drink, bottled water isn't the best choice for contact lens care because it may contain high numbers of likely ocular pathogens. Because brief exposure may contaminate contact lenses, this study stressed the importance of using sterile solutions for rinsing and storing lenses.

New research will continue to develop in all areas of eye care. It's impertinent for us to stay on top of any new information that may benefit us and our practices. Doing so will better able you to provide your patients with more options, which in turn will strengthen their trust in your judgement. 

References are available upon request. To receive references via fax, call (800) 239-4684 and request document #58. (Be sure to have a fax number ready.)

Dr. Jeandervin is a graduate student at the Ohio State University. She is currently studying the effects of near work and myopia and overnight orthokeratology.