Research Digest

Phase 2 dry eye drug results.

Ophthalmologists at the Kresge Eye Institute in Detroit recently undertook a randomized, controlled trial using eye drops containing thymosin β4 (TB4), a naturally occurring peptide, in patients with severe dry eye disease. They reported finding a statistically significant symptom improvement.

The study authors randomized 18 eyes of nine patients, including three patients with graft vs. host disease, to either sham treatment or TB4 eye drops six times daily for 28 days. Ophthalmic assessments were performed, including corneal fluorescein staining and administration of the Ocular Surface Disease Index (OSDI) questionnaire, on a weekly basis over the treatment period, as well as at one month following treatment.

At day 56, the TB4-treated patients reported a 35.1% reduction in ocular discomfort, according to OSDI. In addition, at the same time point, TB4-treated eyes experienced a 49.1% reduction in total fluorescein staining. Both tear film breakup time and tear volume production improved.

Although the trial was limited by the small number of patients, the prospective nature, blinding and placebo control lent particular strength to the evidence. Larger RCTs are being planned.

Incisions and the ocular surface.

To determine what differences exist, produced by incision style, in ocular surface characteristics following strabismus surgery, surgeons in China conducted a large trial of 120 eyes with exotropia.

After randomizing the eyes to either a limbal or fornix incision, the authors administered a battery of ocular surface tests at one, two and four weeks postoperatively. They found that the group with limbal incisions had: increased dry eye symptom scores; decreased tear film breakup time; and corneal sensitivity.

The group with fornix incisions had similar but shorter-term outcomes for tear film breakup time and dry eye symptom scores, but these eyes experienced no change in corneal sensitivity.

The authors conclude that limbal incisions resulted in worse dry eye symptoms and more serious consequences for tear film stability and corneal sensitivity. However, because these changes are nevertheless transient, the authors recommend choosing incision style based on other factors.

DALK for OSD.

Cornea surgeons in South Korea conducted a retrospective review of 15 patients with intractable ocular surface disease (OSD) who received deep anterior lamellar keratoplasty (DALK) with irradiated acellular cornea and amniotic membrane transplantation.

The patients’ indications for surgery included: ocular burns, bacterial or viral keratitis and recurrent band keratopathy, among other disorders. Within two weeks postoperatively, all 15 patients experienced epithelialization. Eighty percent of the patients showed no graft rejection, neovascularization or opacification; the other three developed either neovascularization or opacification but no rejection. The latter cases were treated with PK and had good outcomes at eight months postoperatively.

The authors attribute their impressive outcomes to the sterility of the acellular corneal tissue used in the procedure. In addition, the antifibrotic effects of the amniotic membrane contributed to the successful findings.

Diagnosing Demodex.

Demodex eyelid mites are surprisingly common in humans, and they have been implicated in dry eye disease, blepharitis and other diseases. To facilitate diagnosis, doctors in France used confocal microscopy.

The authors enrolled 48 subjects — eight healthy subjects, 22 with dry eye and 18 with blepharitis — and had their lower eyelids examined with in vivo confocal microscopy. Twenty-five subjects from all three groups also had extracted eyelashes tested.

Of the blepharitis patients with Demodex infections, all of them were correctly diagnosed with confocal microscopy and with examination of extracted eyelashes. However, while confocal microscopy detected 60% of infestations in dry eye patients and 12% in healthy subjects, examination of extracted eyelashes detected only 50% and 0%, respectively. Mites were less likely to be detected if infesting the meibomian glands, rather than the eyelashes.

The authors note that the confocal microscopy was not able to distinguish between the two species of Demodex that parasitize humans. However, they believe that confocal microscopy could be useful for diagnosis of eyelid mites, particularly in centers lacking laboratories for more specific testing.

OSD posttrabeculectomy.

Ophthalmologists in Singapore seeking to characterize the epidemiology of OSD in patients who have undergone trabeculectomy augmented with mitomycin C (MMC) enrolled 12 patients referred to their clinic in a clinical study.

Fifteen eyes of the 12 patients were included in the study; of these 15 eyes, 14 were treated with MMC, while the other was treated with 5-fluoracil. The patients, who were a mean of ~70 years old, had a mean tear breakup time of 5.32 sec and a mean Schirmer score of 6.14 mm/5 min. Several risk factors for dry eye were present, including factors related to anti-glaucoma medications.

After treatment for dry eye, half of these patients experienced improved best-corrected visual acuity, with a mean improvement of two ETDRS lines of vision. The authors recommend greater vigilance regarding dry eye in patients undergoing trabeculectomy with MMC if they are taking an unusually large number of anti-glaucoma medications.

LASIK and persistent postsurgical pain.

This group of researchers, comprised of pain experts, ophthalmologists, geneticists and more set out to understand if LASIK patients, still complaining about pain months after their procedure, were actually experiencing pain or dry eye symptoms. The researchers report that symptoms produced by the corneal nerve cuts made during the surgery resemble the “pathologic neuroplasticity” created in other types of postsurgical pain, such as a coronary artery bypass.

They also report that LASIK patients who go on to develop persistent pain — between 20% and 55% — are the same percentage of those who do likewise who have surgeries such as a bypass, breast removal and thoracotomies.

How to curtail this issue? Since it’s a nerve problem, the authors report, minimize the surgical techniques; it seems sensible, they said. Evidence exists that shows the amount of pain depends on the type of surgical technique.

And lastly, treatment. Accepting the problem is not dry eye and instead pain-related opens up a new world of treatment, including new classes of drug therapy.

Patients with MMP in need of entropion repair

Researchers set out to determine how best to manage patients with mucous membrane pemphigoid, either biopsy confirmed or presumed, who were in need of surgery to repair their eyelids.

The researchers found seven patients with 11 eyes affected by MMP, mostly cicatricial entropion.

The primary outcome measures were disease progression; ocular inflammation control; and how successful the surgery turned out.

As for the results: eight eyes, or nearly 73%, needed a bandage lens to ensure that the cornea was protected while disease control and immunosuppression were attained. Prior to lid surgery, immunosuppressive treatment was used in all patients; the average was 15.1 months; after surgery, the mean was 6.6 months.

All patients enjoyed full surgical success. The patients were followed for an average of 20.8 months. The orals used were mycophenolate and cyclophosphamide; prednisone was used at the same time in four patients.

Identifying risk factors for DMEK preparation

Researchers at the Lions Gate Eye Bank wanted to identify reasons for DMEK preparation failure. Researchers divided the 563 corneal tissues prepared between October 2011 and May 2014 into two groups: those who had failed proper preparation, and those who succeeded DMEK preparation. They found three primary culprits: diabetes, obesity and hyperlipidemia. The tissue of donors whose diabetes was especially long-term had higher levels of failure.

The overall failure rate was 5.2%. Univariate analysis revealed that donors who had diabetes (P=0.000028); its duration (P=0.023); hypertension (P=0.021); and hyperlipidemia or obesity (P=0.0004) had tissue that failed more common. When these tissues were taken out of the failure group, the rate went down to 2.2%.

This work may provide useful information to other eye banks interested in establishing a DMEK program.