Meeting Highlights: ARVO

Small, Tapered Steroid Doses May Control Symptoms

In a double-blind, randomized, controlled pilot study of 20 patients with dry eye, researchers found small, tapered doses of loteprednol effective against dry eye signs and symptoms.

Subjects received either loteprednol etabonate 0.5% (n=10) or NaCl 0.9% (n=10) twice a day for 14 days, tapered to once a day for 15 days, and then every other day for 4 weeks. At baseline, day 14 and day 56, subjects were evaluated for best corrected visual acuity, intraocular pressure, and dry eye signs and symptoms—assessed by the Ocular Surface Disease Index questionnaire, Schirmer I test, tear break-up time (TBUT), lissamine green conjunctival staining, corneal fluorescein staining (CFS) and HLA-DR expression on conjunctival cells.

Treated eyes showed significant decrease in ocular surface inflammation and improved symptoms compared with the control group at days 14 and 56. Although researchers found no significant difference for TBUT or CFS, they noted consistent improvement of lissamine green staining in the steroid group. None of the treated eyes showed significant increase in IOP or worsening visual acuity.

Barabino S. Poster session 3826/D959.

BENNIE H. JENG, MD, RESPONDS:

This study differs from most others in that a tapering dose was used rather than a set dosing at 4 times daily, for example. However, while a significant decrease in inflammation and an improvement in symptoms were seen during the study period, long-term follow up to demonstrate sustained effect is necessary before any conclusions as to the clinical applicability of this regimen can be made. In addition, the use of vehicle rather than NaCl as the placebo in a longer-term study would also make sense. If this regimen can be shown to have positive long-term effects, then patients could be spared higher doses of steroid drops when being treated for dry eyes.

Blink Pattern Affects Ocular Surface Exposure

Researchers analyzed blink pattern and tear-film break-up time and area in 31 adults with mild to moderate dry eye to determine the relationships among these characteristics. Different blink patterns correlated with different amounts of ocular surface exposure. Subjects with longer intervals between blinks and shorter TBUTs had greater ocular surface exposure.

In order to better understand tear film and blink dynamics under natural conditions, investigators used the OPI 2.0 system of tear-film analysis technologies to record TBUT, inter-blink intervals, and tear-film break-up area. They found that subjects demonstrated variable blink rates, with rapid blink patterns serving to make up for tear-film deficiency and with slower blink patterns increasing ocular surface exposure—and presumably ocular surface inflammation.

LaFond AM. Poster session 3845/D978.

BENNIE H. JENG, MD, RESPONDS:

While the results of this study mirror what is generally already believed in clinical practice, the study suggests that this new technology can objectively evaluate the variables of tear-film and blink dynamics. While it may not change clinical management in practice for most patients who have clear-cut diagnoses, this technology could help evaluate patients who do not have straight-forward signs and symptoms of dry eyes. A larger study of such patients, along with outcomes from treatment algorithms based on the objective findings of the OPI 2.0 system may provide clinical utility for our patients in the future.

Ocular Surface Cooler in Sjögren’s Syndrome

Ocular surface temperature cools faster after a blink in dry eyes associated with Sjögren’s syndrome than in normal eyes, especially in the center of the cornea and within 1 second of opening. The temperature drops less dramatically in high humidity, improving dry eye symptoms.

Researchers selected 14 subjects with severe dry eye secondary to Sjögren’s syndrome (tear break-up time < 4 seconds) and 14 subjects with healthy normal eyes for ocular surface temperature measurement. Subjects acclimated to a 24°C, 45% humidity climate-controlled chamber. After 20 minutes, surface temperature was measured by an infrared thermal video camera sensitive to emitted radiation at 0.08°C. Three Sjögren’s subjects repeated the procedure after acclimating for 30 minutes to the chamber with humidity at 85%. Researchers used Matlab software to plot 5 specific areas on the ocular thermograph of eyes fully opened.

All subjects had similar temperatures measured at the root of the nose and on the ocular surface immediately after opening the eye, but the temperature drop rate of the Sjögren’s eyes at all surface points was significantly faster—the fastest at the center of the cornea (-0.276+0.099°C/sec vs. 0.065+0.033°C/sec for the normals, p=0.000)—and larger at the end of the blink cycle (32.79+0.82°C for Sjögren’s vs. 33.73+0.49°C for normals, p=0.000). The rate of the drop in ocular surface temperature was much smaller in the group with high humidity (-0.177+0.040°C/sec, p=0.010).

Wang Q. Poster session 3853/D986.

ELMER TU, MD, RESPONDS:

Perhaps the investigators were clearer than the abstract suggests on their definition of Sjögren’s syndrome, but the criteria of a tear break-up time < 4 seconds may be more indicative of a functionally unstable tear layer not restricted to Sjögren’s syndrome patients. This is important because the findings are most consistent with evaporative tear loss, not exclusive to aqueous tear deficiency, which is a hallmark of Sjögren’s syndrome. The ocular surface cooling may come from radiation of heat on eyelid opening, but is largely from evaporation. A more rapid and complete evaporation of water of a volatile tear film would be most consistent with the mechanism of the evaporative tear loss in these test subjects with short TBUTs of accelerated and longer heat dissipation independent of their Sjögren’s syndrome.

STEPHEN C. KAUFMAN, MD, PHD, RESPONDS:

Objective testing for dry eye disease has been the goal of many studies. Although many objective tests exist, most depend on the control of various variables to improve the accuracy of the tests. Infrared thermography has been proposed as a new means to objectively diagnose dry eye disease.

This study examined infrared thermography of the tear film in normal and Sjögren’s subjects, in a controlled environment chamber. At 45% humidity, the central cornea of the Sjögren’s group was approximately 1°C cooler than the control group. The authors hypothesize that the Sjögren’s patients experience increased evaporation of their tear film, which lowers the temperature of the ocular surface. Also, after blinking the rate of cooling was greater in the Sjögren’s group. This finding suggests that the Sjögren’s group has increased evaporation.

Sjögren’s patients generally have lacrimal gland inflammation, which results in reduced tear production. Increased tear film evaporation is more closely associated with an abnormal tear break-up time and increased exposure. Other ocular thermography studies confirmed that tear break-up time was highly correlated with dry eye disease. Paradoxically, other studies by Morgan and Mori found increased ocular surface temperatures associated with dry eye disease. Clearly, additional testing is required, with more adjunctive testing, to better understand and define the associations of infrared thermography with different etiologies of dry eye disease.

Acupuncture Offers No Treatment Benefit for Dry Eye

In a prospective, double-blind, randomized, controlled study of patients with dry eye, researchers found no objective beneficial effects from acupuncture therapy on widely used clinical indicators for the condition.

Volunteers were randomized to receive two treatment sessions, separated by 24 hours, of acupuncture (n=8) or a sham procedure (n=9). Outcomes were assessed at baseline, 1 week, and 1, 3 and 6 months after treatment using McMonnies and Ocular Surface Disease Index questionnaires, Schirmer’s test with and without anesthesia, fluorescein tear break up time, lissamine green staining and corneal surface regularity index. Researchers found no significant improvement in these measurements after acupuncture treatment.

Shaw KS. Poster session 3839/D972.

STEPHEN C. KAUFMAN, MD, PHD, RESPONDS:

Alternative medicine is always of interest as a possibly overlooked source of treatment for diseases that have no good cure. Some acupuncture practitioners have proposed to have successfully treated dry eye. The authors of this study did not detect a statistically significant difference between the treatment and the sham groups. Their groups were small, but the testing was relatively extensive.

A detailed look at the findings does confirm that the there was a difference between the dry eye patients in the treatment group verses the sham treatment group in their questionnaire scores, with the sham group having a higher (more symptomatic) score. The general P-values between the treatment groups were not significant for most tests, but 4 instances exhibited statistically significant differences between the 2 groups within the 3 posttreatment time points: TBUT was improved more in the sham treatment group at 2 time points, the Schirmer was improved more in the sham treatment group at 1 month, and the McMonnies score was improved more in the sham treatment group at 1 time point. Although it was not statistically significant, the sham group had a greater degree of improvement in the McMonnies and OSDI score at every time point.

Does this mean the sham treatment is a cure for dry eye? Unfortunately, we cannot make that conclusion. Larger studies are necessary to clarify these issues. What we may be able to say is that we cannot underestimate the placebo effect.