Leaders in their respective specialties came together at the American Academy of Optometry 2015 meeting in New Orleans to share their latest research in dry eye and glaucoma.
Hot topics in dry eye focused on study results from lifitegrast, Shire’s dry eye therapy pending FDA approval; Refresh Optive Gel Drops, Allergan’s newest rewetting drop with glycerin; and MiboFlo, MiBo Medical Group’s lid massager.
More from AAO: The pros and cons of the latest dry eye tech
Editorial Advisory Board member Walter O. Whitley, OD, FAAO, summarized three randomized trials for lifitegrast. The drug is a small molecule integrin antagonist that interferes with binding of ICAM-1 to the integrin LFA-1 on the T-cell surface, inhibiting T cell recruitment and activation associated with dry eye disease.
Learning from Study 1: Met pre-specified sign endpoint, mean change from baseline to day 84 in inferior corneal staining score (ICSS) and there was a dose-response relationship for signs and symptoms of dry eye with greatest efficacy for 5.0% solution vs. 0.1% and 1.0%.
Learning from Study 2: Met the sign (ICSS) but not the symptom co-primary endpoint. Lifitegrast effect on ICSS was more pronounced in less symptomatic subjects.
Learning from Study 3: Lifitegrast significantly improved eye dryness score and all pre-specified secondary symptom endpoints achieved statistical significance. Lifitegrast failed to separate sign endpoint from placebo in the more symptomatic population.
As in previous dry eye disease (DED) research, outcomes for signs and symptoms of DED are poorly correlated in lifitegrast clinical trials.
For the eye dryness score, there may be a “floor effect,” as seen in Study 2, in which efficacy can be demonstrated only when baseline symptoms are sufficiently severe. In contrast, subjects with high baseline ICSS grades may have underlying conditions not responsive to a short course of treatment, or there may be difficulties in grading the inferior corneal staining score (ICSS).
Because of the paradoxical relationship between signs and symptoms of DED observed in the lifitegrast trials, it may not be possible to achieve statistical success with the coprimary endpoints (signs and symptoms) in the same study.
In two studies, lifitegrast improved signs of DED in subjects with mild to moderate baseline symptomatology. In two studies, lifitegrast improved symptoms of DED in subjects with moderate to severe baseline symptomatology.
In all three studies, lifitegrast appeared to be well tolerated in with no serious ocular treatment-emergent adverse events.
Next: Refresh Optive Gel Drops
Refresh Optive Gel Drops
Chris Lievens, OD, FAAO, talked about study results featuring an enhanced viscosity eye drop for moderate to severe dry eye disease.
“Carboxymethyl cellulose (CMC) may be combined with small molecules, such as glycerin, which can enter ocular cells and improve hydration,” he says. “Higher concentrations, such as 1%, enhance viscosity and ocular residence time.”
The study aimed to compare 1% CMC and glycerin vs. 1% CMC alone in 188 patients. The primary efficacy measure was Ocular Surface Disease Index (OSDI), with secondary measures of tear break-up time (TBUT), Schirmer with anesthesia, and subject survey on symptoms and acceptability.
OSDI scores improved significantly from baseline in both treatment groups at Day 30.
TBUT showed significant improvement from baseline at Day 7 with the test product; at Day 30, both groups had significant improvement.
Combined corneal and conjunctival staining showed significant improvement from baseline in both groups at Day 7. At Day 30, both groups had significant improvements from baseline combined staining. Only the test product showed improved corneal staining at both Days 7 and 30.
Ocular symptoms measured by a visual analog scale also improved from baseline in both groups. There were no significant changes in Schirmer test results.
Acceptability results indicated some transient blur with both of these more viscous products but were otherwise positive. Reported study product usage was slightly lower with test product than CMC
Overall, the test product was safe and effective for relief of dry eye signs and symptoms.
“These results support the use of CMC-glycerin eye drops as an effective treatment to reduce signs and symptoms of dry eye disease,” says Dr. Lievens.
Leslie O’Dell, OD, FAAO, wanted to determine if a 12-minute treatment with MiBoFlo would improve patient symptoms.
She used the SPEED questionnaire to gather subjective information and OSDI for clinical data, then treated only one eye per patient with MiBoFlo.
Her results showed no impact on symptoms and no significant improvement for SPEED or OSDI scores. However, meibomian secretion scores did significantly improve for gland expression with a single 12-minute treatment. In addition, there was significant improvement in baseline in the treatment group.
“I suggest to combine treatment with in-office manual expression of glands,” she says. “Patients tolerate it very well. This study showed me there was a void in what we do with meibomian gland expression. We need treatment options, and it’s good to have a step by step approach.
Dr. O’Dell recommends the LEO method: liquefy, express, observe.
She noted that there is no CPT code at this time for MiBoFlo treatments; practitioners need to charge fee for service.
Brett King, OD, FAAO, shared the results of his research on using en face and circumpapillary ocular coherence tomography (OCT) to predict functional loss in glaucoma patients.
Dr. King and his team tested one eye in each of the 17 subjects participating in an ongoing prospective study to gather spectral-domain OCT (SD-OCT) scans and perimetric sensitivities on a custom testing station who had completed three visits. Testing was restricted to 18 of the 24-2 locations above and below the nasal portion of the horizontal midline.
Four examiners were then asked to review the en face and circumpapillary RNFL images for the subjects with glaucoma. The visual field loss was masked, and the examiners were asked to predict which of the locations would show a defect. The 17 subjects and four examiners provided 68 predicted fields for both en face and circumpapillary.
The study found that both en face and circumpupillary often allow the examiner to predict visual field defects, and Dr. King says they may do so in a complementary manner. He says that en face RNFL images may be a potential new tool for eyecare providers to translate structure to function in management of glaucoma. Dr. King believes this warrants further training for the examiners and refinement of this potential tool.
Next: The prevalence of 10-2 visual field loss
The prevalence of 10-2 visual field loss
My Tho Karin Tran, OD, MS, presented the paper that she summarized in the Academy Press Conference earlier this week
. She says that recent studies have found that glaucomatous visual field loss within the central 10 degrees is not uncommon, which may substantially impact a patient’s quality of life. Dr. Tran’s study aimed to determine the prevalence of 10-2 visual field loss in glaucoma patients and glaucoma suspects and to examine factors that may predict the presence of 10-2 visual field loss.
The study, which took place at Albuquerque VA Medical Center, involved patients participating in a prospective, longitudinal glaucoma research study in which 10-2 visual field tests were included. All of the patients had a diagnosis of primary open-angle glaucoma, normal-tension glaucoma, ocular hypertension, or were glaucoma suspect who had reliable 24-2 and 10-2 visual field tests as well as spectral domain OCT RNFL scans within six months of the 10-2 test.
Researchers used previously published cluster criteria to identify and calculate the prevalence of 10-2 visual field loss before and after staging patients according to 24-2 visual field loss. They used regression analyses to investigate factors associated with presences and severity of 10-2 visual field loss.
Of the 173 patients, 10-2 visual field loss was detected in 81. Of those patients, five had detected 10-2 visual field loss out of those that had no 24-2 visual field loss; 38 out of 47 who had mild 24-2 visual field loss; 18 out of 19 who had moderate visual field loss; and 20 out of 20 patients who had advanced 24-2 visual field loss. Dr. Than says that the mean lowest-eye global RNFL value was 62 µm in patients with vs. 85 µm without 10-2 visual field loss.
Dr. Than says the results indicate measureable visual field loss within the central 10 degrees is very common in glaucoma, even when 24-2 VF loss is mild. She says eyecare providers should consider 10-2 testing in all patients with glaucoma, particularly when OCT-RNFL scans are abnormal.
Next: IOP and long anterior zonule trait
IOP and long anterior zonule trait
Daniel Roberts, OD, PhD, FAAO, investigated the relationship between intraocular pressure (IOP) and long anterior zonule (LAZ) trait, which is characterized by zonular fibers that extend more centrally than usual on the anterior lens capsule and can result in pigment liberation from the back of the iris.
Study participants were examined for LAZ, and researchers collected information about systemic and ocular health status through standard examination and with a questionnaire. Researchers used multivariate regression modeling to explore the relationship between IOP and LAZ.
The study found that eyes with LAZ tended to have higher IOP than eyes without the trait, which Dr. Roberts says is consistent with the hypothesis that glaucoma risk may be higher among people with LAZ.
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