Acupuncture and dry eye: current perspectives. A double-blinded randomized controlled trial and review of the literature.

Purpose: Dry eye disease (DED) is a common disorder that negatively impacts quality of life and vision. Prior studies have shown some benefit of acupuncture for dry eye, but very few have included control group to mitigate placebo effect. This study was designed with a sham acupuncture control group to evaluate true acupuncture treatment effect. Methods: This is a prospective, randomized, double-blinded, sham-acupuncture-controlled trial. Acupuncture treatment for dry eye was performed as per the Niemtzow Protocol. Twenty-four patients received true acupuncture and twenty-five received sham acupuncture. Treatment efficacy was assessed by the Ocular Surface Disease Index (OSDI) Questionnaire, ocular surface staining, tear flow, tear film break-up time (TBUT), and a general questionnaire. Atmospheric data were collected to control for the effect of atmospheric conditions on symptoms of dry eye. Results: OSDI scores in the treatment group improved compared to baseline (1 week, p<0.01, 1 month p<0.05, 3 months p<0.05, and 6 months p<0.01). OSDI scores in the control group improved, but did not reach significance (p=0.09). Secondary outcome measures showed no significant improvement in TBUT, Schiermer's Test, ocular surface grading, or artificial tear application. However, at 3 months, a significant reduction in the frequency of eye closing was observed among participants receiving true acupuncture treatment when compared to baseline (p=0.002). Furthermore, intragroup analysis showed significant reduction in symptoms of discomfort (p=0.01), dryness (p=0.001), scratchiness (p=0.001), and redness (p=0.01) in the true acupuncture group at 3 months. Conclusion: Both true and sham acupuncture improved OSDI at 1 week after treatment, however, the improvement in OSDI was significantly greater in the true treatment groups than the sham group at 6 months after acupuncture. True acupuncture treatment improved many subjective assessments of dry eye symptoms, however, other common indicators used to objectively assess dry eye (tear flow, corneal staining, TBUT) remained unchanged. While there were trends towards improvement in the sham acupuncture group, this did not reach statistical significant during the study period. This suggests a true treatment effect of acupuncture rather than a placebo effect. Acupuncture can, therefore, be an effective adjunct to routine clinical treatment of dry eye.

Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%.

OBJECTIVE: The purpose of this work was to evaluate the effect of loteprednol etabonate (LE) before the initiation of topical cyclosporine A (tCsA) therapy in patients with mild-to-moderate dry eye disease. Prospective, multicenter randomized double-masked parallel group clinical study (NCT00407043). METHODS: Hundred and eighteen patients with dry eye disease were randomized to receive either LE and tCsA (n=61) or artificial tears (AT) and tCsA (n=57). Hundred and twelve patients completed the study (LE: n=57, AT: n=55) and are included in the data analysis. Patients self-administered either LE or AT for 2 weeks 4 times per day, followed by tCsA twice per day accompanied by either LE twice per day or AT twice per day for an additional 6 weeks of treatment. Primary outcome measures included the Ocular Surface Disease Index (OSDI) questionnaire, the Likert scale using standardized facial expressions, lissamine green staining, fluorescein staining, and the Schirmer test. Additional measures included global self-assessment, and safety outcomes included slitlamp examination, intraocular pressure, and assessment of visual acuity. RESULTS: Loteprednol etabonate pretreatment significantly reduced tCsA stinging (P<0.05). Both groups showed significantly improved OSDI scores at the 14-, 30-, and 60-day visits. Loteprednol etabonate showed significantly more OSDI improvement than AT. Both pretreatment strategies improved global self-assessment scores, Schirmer test, fluorescein staining, lissamine staining, and adjunctive AT use. Loteprednol etabonate showed superior improvement in Schirmer test, fluorescein staining, and lissamine staining. Intraocular pressure did not increase in either group. CONCLUSIONS: Loteprednol etabonate induction therapy 2 weeks before the initiation of long-term tCsA treatment for chronic dry eye disease provides more rapid relief of dry eye signs and symptoms with greater efficacy than tCsA and AT alone.

Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the inhibition of corneal transplant rejection in a rat cornea transplant model.

PURPOSE: The cornea is one of the most commonly transplanted tissues. The morpholino-oligomer antisense compound AVI-5126 suppresses expression of proto-oncogene c-myc, a key factor in transplant rejection. AVI-5126 was evaluated in a rat cornea transplant model. METHODS: Donor corneas obtained from August x Copenhagen Irish rats were stored in Optisol™ containing 1.0 or 0.5 mg/mL AVI-5126 or Optisol alone for 24 h before transplant. Recipient Lewis rats were treated topically 3x/d with TobraDex™ and with 1.0 or 0.5 mg/mL of AVI-5126 or saline with daily monitoring for rejection using a modified McDonald-Shadduck Slit Lamp Scale. Using the high-performance liquid chromatography technique, the stability of AVI-5126 (0.5 mg/mL) in Optisol was evaluated for 30 days. AVI-5126 corneal transport was measured using Ussing chamber mounted rabbit corneas. The potential ocular toxicity of AVI-5126 (0.5 mg/mL) was evaluated after 8 days of 3x/d topical application in rats and in-vitro by incubation of human corneas for 8 days. RESULTS: Cornea storage in Optisol containing 1.0 mg/mL AVI-5126 plus post-transplant topical tid AVI-5126 (1.0 mg/mL) application significantly increased graft survival (7.0±1.6 days) versus 5.0±0.8 days for Optisol alone storage plus post-transplant topical tid saline application (P<0.001). After 30 days of storage, no significant degradation of AVI-5126 in Optisol was noted by high-performance liquid chromatography analysis. After 24 h, 5 µg/mL (1% of total dose) crossed the corneas mounted in Ussing chambers. Neither extended topical application of AVI-5126 to rats nor incubation of human corneas in AVI-5126 decreased endothelial cell density. CONCLUSIONS: Graft rejection was significantly delayed after pretransplantation storage of graft corneas in Optisol containing AVI-5126 followed by topical application of AVI-5126 post-transplantation. AVI-5126 was well tolerated, stable, and effectively penetrated the cornea.

Comparison of topical and intravenous administration of WIN 55-212-2 in normotensive rabbits.

OBJECTIVE: This study compares the effect of topical versus intravenous (IV) administration of synthetic WIN 55-212-2 (WIN) or timolol on intraocular pressure (IOP). METHODS: WIN or timolol were administered either topically or by IV in normotensive New Zealand white rabbits. IOP was measured at baseline and 30, 60, and 120 min after administration (n = 4 per group). Blood pressure (BP) and heart rate (HR) were measured concomitantly with IOP. RESULTS: IV administration of 0.1 mg/kg WIN reduced IOP by 30% after 30 min, which continued to decline for up to 120 min. Timolol injection (25 mu g/kg) also reduced IOP by 25% after 30 min but was not sustained. In comparison, both topical WIN (1.0%) and timolol (0.5%) reduced IOP by 20% from baseline after 30 min. IV injection of either WIN or timolol significantly reduced HR to 155.4 +/- 11.4 bpm and 165.9 +/- 11.1 bpm, respectively, from a baseline of 256.3 +/- 9.9 bpm. Topical administration was well tolerated and did not affect behavior, BP, or HR. CONCLUSION: Topical administration of either WIN or timolol did not decrease IOP as much as IV administration, but the lack of systemic or local toxicity could make it the safer alternative.

Topical WIN55212-2 alleviates intraocular hypertension in rats through a CB1 receptor mediated mechanism of action.

INTRODUCTION: Systemically administered cannabinoids can reduce intraocular pressure (IOP), but produce undesirable cardiovascular and central nervous system effects. In a chronic model of ocular hypertension, we examined the efficacy of acute topical administration of WIN55212-2 (WIN) in a novel commercially available vehicle and in combination with timolol. METHODS: IOP was chronically elevated by the surgical ligature of vortex veins in Sprague Dawley rats. IOP was measured by using Goldmann applanation tonometry. IOP, blood pressure (BP), and heart rate (HR) were measured at baseline and 30, 60, 90, and 120 min after the topical administration of WIN 1.0%, 0.25%, 0.06%, or 0.015%, the commercially available vehicle, timolol 0.5%, or a combination of WIN and timolol. SR141716 (CB1 antagonist) or SR144528 (CB2 antagonist) was administered topically 30 min before WIN to determine receptor specificity. To determine ocular and systemic penetration, 3H WIN 55212-2 was administered topically and tissues were collected at 60 and 120 min. Ocular irritation was evaluated by slit-lamp examination (SLE) at baseline and 120 min. RESULTS: WIN significantly decreased IOP in the hypertensive eye, with no BP or HR effects. SR141716 pretreatment significantly inhibited the IOP effects of WIN 1.0% in a dose-dependent manner, while SR 144528 was not as effective. No significant additive effects were observed by combining WIN (0.5% or 1.0%) with timolol 0.5%. WIN was retained in ocular tissue with a t1/2 of 80-100 min. SLE at 120 min revealed no solvent or drug-related toxic effects. CONCLUSIONS: In a chronic ocular hypertensive rat model, topically applied WIN is an effective, nontoxic ocular hypotensive agent with no hemodynamic side-effects. This effect was predominantly CB1 receptor mediated, but some CB2 contribution could not be ruled out.