Is there a role for tapered topical dose steroidal treatment for dry eye disease? A randomized, pilot study.

PURPOSE: To evaluate the effect of tapered doses of loteprednol-etabonate in dry eye disease patients. MATERIALS AND METHODS: Dry eye and treatment outcomes were assessed by Schirmer I test, tear BUT, lissamine green conjunctival staining, fluorescein corneal staining, and HLA-DR expression on conjunctival cells. Patients received either loteprednol-etabonate 0.5% twice daily for 14 days tapered to once daily for 14 days, and then twice weekly for 28 days (n = 10), or NaCl 0.9%. RESULTS: A significant decrease of ocular surface inflammation and improvement of symptoms was recorded in the study group compared with controls at days 14 and 56. Change from baseline in HLA-DR expression in CD45+ conjunctival cells was significantly higher in treated patients at day 14. Intraocular pressure and best corrected visual acuity were preserved in all treated eyes. CONCLUSIONS: Tapered doses of loteprednol etabonate 0.5% suspension controlled ocular surface inflammation, improving dry eye symptoms.

Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events.

PURPOSE: To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). METHODS: Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). RESULTS: The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. CONCLUSIONS: Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

Bromfenac ophthalmic solution 0.09 %: human aqueous humor concentration detected by high-performance liquid chromatography.

The purpose of this study was to evaluate the aqueous humor concentrations of bromfenac ophthalmic solution 0.09 % in patients undergoing phacoemulsification. Patients requiring cataract extraction received one drop (50 µL) of bromfenac 0.09 % solution in the eye to be operated, before bedtime the day before surgery or the morning of the surgery. The last administration was recorded. At the time of paracentesis, an aqueous humor sample was collected with a 30-gauge needle attached to a TB syringe and was later analyzed by high-performance liquid chromatography for drug concentration. 188 treated volunteers and 48 control, untreated, subjects were included in the study. The mean aqueous concentration of bromfenac in the treated group was 37.60 ± 68.86 and 0 nM (nmol/L) in the control group (p < 0.0001). Correlation coefficient in bromfenac group between time elapsed from instillation and drug concentration was -0.16 (p not significant). Bromfenac showed properties of good penetration and stable concentration in aqueous humor up to about 12 h after instillation.

Evaluation of oxidative stress levels in the conjunctival epithelium of patients with or without dry eye, and dry eye patients treated with preservative-free hyaluronic acid 0.15 % and vitamin B12 eye drops.

PURPOSE: Increased levels of oxidative stress have been seen in animal models of dry eye and in the conjunctival epithelial cells of patients with Sjögren's syndrome. The aims of this study were to compare the levels of oxidative stress in patients with dry eye and patients without dry eye and to evaluate the effects of treatment with preservative-free eye drops containing hyaluronic acid 0.15 % and vitamin B12 on oxidative stress and dry eye symptoms. METHODS: Three cohorts of patients who were to undergo planned cataract surgery were enrolled: patients with dry eye randomized to either no treatment (n = 29) or treatment (n = 32) with hyaluronic acid/vitamin B12 eye drops, and patients without dry eye (n = 42). Patients were assessed by Schirmer's type I test, fluorescein clearance test (FCT), Break Up Time (BUT), and Ocular Surface Disease Index (OSDI). Lipid peroxidation, a marker of oxidative stress, was assessed by LP-CHOLOX test. RESULTS: Compared with patients without dry eye, patients with dry eye had significantly increased levels of oxidative stress, higher OSDI and FCT scores, and significantly lower Schirmer's test and BUT scores. Treatment with eye drops containing hyaluronic acid 0.15 % and vitamin B12 was associated with significantly reduced levels of oxidative stress and OSDI and FCT scores and significantly increased Schirmer's test and BUT scores. CONCLUSIONS: These findings indicate that oxidative stress is associated with dry eye and that hyaluronic acid/vitamin B12 eye drops may attenuate oxidative stress and inflammation, improving dry eye symptoms. Further study in controlled clinical trials is warranted.

Systemic omega-6 essential fatty acid treatment and pge1 tear content in Sjögren's syndrome patients.

PURPOSE: To determine the effect of oral omega-6 essential fatty acids on PGE(1) tear content and signs and symptoms of ocular discomfort in patients with Sjögren's syndrome (SS). METHODS: This randomized, double-masked, controlled, clinical trial involved 40 patients with primary SS, divided into two groups: group 1: 20 patients (18 women, 2 men; mean age, 36.9 +/- 7.9 years [SD]) treated for 1 month with linoleic acid (LA; 112 mg), and gamma-linolenic acid (GLA; 15 mg) administered twice daily; group 2: 20 patients (19 women, 1 man; mean age, 36.3 +/- 5.5 years) treated twice daily with placebo. Patients underwent three examinations: at baseline (T0), after 1 month of treatment (T1), and 15 days after suspension of treatment (T2). At each examination, the following tests were performed: tear sampling (2 microL) from the inferior meniscus, tear break-up time (BUT), fluorescein stain of the ocular surface, and tear basal secretion. A symptom score was also obtained at each examination. PGE1 was evaluated by enzyme immunoassay. The primary efficacy variable was PGE1 content of tears. RESULTS: The tear PGE1 levels were significantly increased in group 1 at T1 versus T0 (PGE1 level: T0, 44 +/- 5.4 ng/mL; T1, 58.3 +/- 5.5 ng/mL; P < 0.01 versus T0 and group 2 at T1). At examination T2, a statistically significant reduction of PGE1 levels toward baseline was observed (45.7 +/- 5.2 ng/mL; P < 0.01 versus T1). A statistically significant reduction of symptom score was observed in group 1 at examination T1 (P < 0.01 versus T0 and group 2 score). At examination T2, the symptom score was significantly higher than T1 but remained lower than T0. The corneal fluorescein stain in group 1 showed a statistically significant improvement at examination T1 versus T0 and group 2 (P < 0.01). This improvement was also present at T2 (P < 0.02). No statistically significant differences were found for the other tests. No statistically significant changes were observed in the patients in group 2 at all examination time points. CONCLUSIONS: Omega-6 administration increases the PGE1 levels in tears of patients with SS and improves ocular surface signs and symptoms of ocular discomfort.

Distribution of conjunctival HLA-DR expression and the pathogenesis of damage in early dry eyes.

PURPOSE: To examine the expression of HLA-DR, a marker of inflammation, in the early stages of dry eye disease and to locate the appearance of this marker on specific areas of the bulbar conjunctiva. METHODS: Dry eye patients were identified and their condition classified as mild (n = 16) or moderate (n = 16) based on Schirmer testing, vital staining, tear break-up time, and symptom questionnaire scores. Brush cytology was used to collect epithelial cells from the nasal, temporal, and superior conjunctivae of patients and age-matched controls. HLA-DR positive cells were detected by immunohistochemical staining and quantified. RESULTS: Patients with moderate dry eye had the highest rate of conjunctival HLA-DR-positive cells, with significantly higher rates than controls regardless of which region of the conjunctiva was sampled (P < 0.01). The mild dry eye group had similar rates of HLA-DR-positive cells in the superior conjunctival region compared with controls. However, in the nasal and temporal regions, they displayed a significantly higher rate of HLA-DR-positive cells than controls (P < 0.01) and the nasal region showed a significant difference (P < 0.01) when compared with the temporal one. Some of these mild dry eyes had no vital staining. CONCLUSIONS: The HLA-DR expression pattern in mild and moderate dry eyes appears to reflect disease progression. Overexpression of HLA-DR in mild dry eyes showing no vital staining suggests that inflammation may be a primary cause of ocular surface damage. These data support the use of immunomodulatory drugs in the treatment of dry eye disease.

Effect of linoleic acid and gamma-linolenic acid on tear production, tear clearance and on the ocular surface after photorefractive keratectomy.

BACKGROUND: The aim of this study was to evaluate the effect of linoleic acid (LA) and gamma-linolenic acid (GLA), both precursors of PGE(1), on tear production, tear fluorescein clearance and on the ocular surface after photorefractive keratectomy (PRK). METHODS: Sixty subjects (age 25+/-10 years; refractive error -3+/-2 diopters (spherical equivalent), mean +/- standard deviation) undergoing PRK were enrolled. The inclusion criteria were: Schirmer 1 test >10 mm/5 min, no corneal fluorescein staining, low irritation symptoms (questionnaire score <5), standardised visual scale (to evaluate tear fluorescein clearance) score <3. Patients were randomly divided into two groups. One group of 31 subjects was treated once daily orally with tablets containing LA (28.5 mg) and GLA (15.1 mg) (from 3 days before PRK to 1 month after PRK). The control group (29 subjects) underwent PRK and received no treatment with LA and GLA. A symptoms questionnaire, Schirmer 1 test and fluorescein clearance test (FCT) using the standardised visual scale were performed before starting therapy (T(0)) and 30 days after PRK (T(1)). RESULTS: All patients completed the study. The Schirmer 1 test varied from 16.3+/-6.9 (T(0)) to 17.6+/-7.2 (T(1)) for the treated group and from 18.3+/-6.2 (T(0)) to 15.7+/-7.4 (T(1)) for the untreated group ( P<0.0001, two-tailed unpaired t-test). FCT was 1.9+/-0.6 at T(0) and 1.6+/-0.8 at T(1) for the treated group and 1.7+/-0.7 at T(0) and 2.0+/-0.9 at T(1) for the untreated group ( P<0.0001). The symptoms score was 4.7+/-1.9 at T(0) and 7.6+/-7.2 at T(1) for the treated group and 4.2+/-2.0 at T(0) and 10.1+/-7.6 at T(1) for the untreated group ( P<0.05). CONCLUSION: Reduced corneal sensitivity has already been proved after PRK. This could be the main reason for a decrease in tear production and for a reduced blinking rate leading to delayed tear clearance. The oral precursors of PGE(1), LA and GLA, could be helpful in increasing tear production and clearance after PRK.

Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component.

PURPOSE: To evaluate the efficacy and anti-inflammatory activity of systemic linoleic (LA) and gamma-linolenic acid (GLA), which decrease chronic inflammation in rheumatoid arthritis, on the ocular surface of patients with keratoconjunctivitis sicca. METHODS: In a randomized clinical trial, 26 patients with aqueous-deficient keratoconjunctivitis sicca were consecutively selected from patients presenting to Department of Neurosciences, Ophthalmology and Genetics, University of Genoa. The diagnosis was based on dry eye symptom survey score, Schirmer-1 test values, positive vital staining with lissamine green, and fluorescein break-up time (FBUT). All patients had ocular surface inflammation based on HLA-DR expression, a major histocompatibility class II antigen, on epithelial bulbar conjunctiva samples. The subjects were randomly divided into two groups of 13 patients each. The study group received tablets containing LA (28.5 mg) and GLA (15 mg) twice daily for 45 days and used tears; the control group received a tear substitute and a placebo tablet for 45 days. RESULTS: Statistically significant changes in symptoms (p < 0.005), lissamine green staining (p < 0.005), and ocular surface inflammation (p < 0.05) occurred in the study group compared with controls. HLA-DR expression varied from 58.5 +/- 14.1% positive conjunctival cells to 41.3 +/- 18.9% in the treated group and from 61.4 +/- 21.9% to 58.0 +/- 13.3% in the controls. No statistically significant difference between groups was found for FBUT and the Schirmer-1 test. CONCLUSIONS: Therapy with LA and GLA and tear substitutes reduces ocular surface inflammation and improves dry eye symptoms. Long-term studies are needed to confirm the role of this new therapy for keratoconjunctivitis sicca.

Pharmacokinetics and bioavailability of a Ginkgo biloba extract.

The aim of the present study was to assess the bioavailability of the main active ingredient in Ginkgo biloba extract, ginkgolid B. The study also focused on the pharmacokinetics of two different dosage regimens for orally administered Gingko biloba extract, 80 mg once daily and 40 mg twice daily for 7 days. Twelve healthy volunteers took part in the study. They were randomly assigned to one of the two treatment groups: 40 mg twice daily or 80 mg once daily, with an interval of 21 days between cycles. Statistical analysis was used to assess the main pharmacokinetic parameters. The results show that a dosage of 40 mg twice daily (every 12 hrs) is accompanied by a significantly longer half-life (t1/2) and mean residence time (MRT) than a single 80 mg dose, even though the latter causes a higher concentration peak (Cmax). The maximum concentration time (Tmax) is 2.3 hrs after administration in both treatments.