The Use of Junfeng BFS Water (JBW) in Dry Eye Syndrome.

BACKGROUND AND PURPOSE: Junfeng BFS Water (JBW) is normal drinking water treated by an extremely low frequency electromagnetic field with certain electromagnetic oscillations. This leads to a change in physical water properties, such as an increase in permittivity and an increase in dissolved oxygen. Animal studies show that JBW has certain biological effects, such as improvement in microcirculation, cell hydration, and blood rheology. In a clinical study, we were able to show an improvement in ocular blood flow after drinking JBW. Since people drinking JBW reported an improvement in dry eye symptoms, we wanted to examine tear film stability by determining the break-up time (BUT) through patient interviews. METHODS: Sixty patients (120 eyes) were age matched and randomized in a double-blind study using the JBW device, or an identical looking nonworking device, without influence on drinking water (control group). All participants had to drink 2 liters of water per day over a period of 2 months. All study subjects underwent a complete ophthalmological examination, including measurement of BUT at day 0, 1 month, and 2 months. At the same time, the patients were interviewed about their eyes, their subjective feelings, and their vision. Statistical analysis was performed using the IBM SSPS program. Bivariate statistics were performed using the ANOVA test. The level of significance was a = 0.05 RESULTS: The increase in BUT was significantly higher in both eyes (a< = 0.01) of the population drinking JBW after 1 and 2 months compared to the control group using untreated water. This result was confirmed in patient interviews. Therefore, patients drinking JBW judged the question "do you have tired eyes?" significantly better (a = 0.04) than the control group after 1 month. Eighty percent of the JBW group continued to drink JBW 6 months after the end of the study, and more than 50% were able to reduce treatment with artificial tears or stop it completely. CONCLUSIONS: Apart from an improvement in microcirculation, drinking JBW seems to have a positive effect on dry eye syndrome. Mechanisms are still unknown, and improvement in microcirculation of the lacrimal gland should be discussed. If our results can be confirmed in a larger study, and with more sophisticated methods, we see a potential for JBW's use as an additive to conventional dry eye therapy.

First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-ß2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery.

PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-ß2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6.75 µg, 22.5 µg, 67.5 µg or 225 µg, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of approximately 0.3 µM, 1 µM, 3 µM or 10 µM after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc assessment. RESULTS: In total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (±SD) for dose levels 1, 2, 3, and 4 were at Day 43 9.8 mmHg ± 1.0 mmHg, 11.3 mmHg ± 6.7 mmHg, 5.5 mmHg ± 3.0 mmHg and 7.5 mmHg ± 2.3 mmHg SD; and at Day 85 9.7 mmHg ± 3.3 mmHg, 14.2 mmHg ± 6.5 mmHg, 5.8 mmHg ± 1.8 mmHg and 7.8 mmHg ± 0.6 mmHg, respectively. In contrast to IOP values for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period. CONCLUSION: This first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 µg or 225 µg at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.

Efficacy and safety of preoperative IOP reduction using a preservative-free fixed combination of dorzolamide/timolol eye drops versus oral acetazolamide and dexamethasone eye drops and assessment of the clinical outcome of trabeculectomy in glaucoma.

INTRODUCTION: To demonstrate that preoperative treatment for 28 days with topical dorzolamide/timolol is non-inferior (Δ = 4 mm Hg) to oral acetazolamide and topical dexamethasone (standard therapy) in terms of intraocular pressure (IOP) reduction 3 and 6 months after trabeculectomy in glaucoma patients. MATERIALS AND METHODS: Sixty-two eyes undergoing trabeculectomy with mitomycin C were included in this monocentric prospective randomized controlled study. IOP change between baseline and 3 months post-op was defined as the primary efficacy variable. Secondary efficacy variables included the number of 5-fluorouracil (5-FU) injections, needlings, suture lyses, preoperative IOP change, hypertension rate and change of conjunctival redness 3 and 6 months post-op. Safety was assessed based on the documentation of adverse events. RESULTS: Preoperative treatment with topical dorzolamide/timolol was non-inferior to oral acetazolamide and topical dexamethasone in terms of IOP reduction 3 months after trabeculectomy (adjusted means -8.12 mmHg versus -8.30 mmHg; Difference: 0.18; 95% CI -1.91 to 2.26, p = 0.8662). Similar results were found 6 months after trabeculectomy (-9.13 mmHg versus -9.06 mmHg; p = 0.9401). Comparable results were also shown for both groups concerning the classification of the filtering bleb, corneal staining, and numbers of treatments with 5-FU, needlings and suture lyses. More patients reported AEs in the acetazolamide/dexamethasone group than in the dorzolamide/timolol group. DISCUSSION: Preoperative, preservative-free, fixed-dose dorzolamide/timolol seems to be equally effective as preoperative acetazolamide and dexamethasone and has a favourable safety profile.

Changes in quality of life in visually impaired patients after low-vision rehabilitation.

The objective of the study was to assess the impact of low-vision aids on quality of life. Interviews included a modified version of the National Eye Institute Visual Functioning Questionnaire (Modified German NEI VFQ-25), the Hospital Anxiety and Depression Scale, the Mini-Mental State Examination Blind, and Indicators of the Rehabilitation Status. These were conducted before and 5 months after low-vision rehabilitation that involved recommendation of devices and instructing patients on how to use them. Of a total of 88 patients interviewed before low-vision rehabilitation, 50 patients could be reached for the follow-up interview. A huge proportion of the sample reported clinically significant depression (30%) or anxiety (30%). There were no differences between participants or dropouts. After fitting of low-vision devices, patients reported a significant improvement in perceived near tasks (P<0.01), social functioning (P<0.01), and reading ability (P<0.001). The magnitude of change was moderate. No significant changes were found in Hospital Anxiety and Depression Scale, Mini-Mental State Examination Blind, and Indicators of the Rehabilitation Status. Low-vision rehabilitation appears to have a broader effect than simply improving visual performance, as it may positively influence social functioning. Even though this study had no control group, the influence of low-vision aids on social functioning has not been reported before and should encourage their use.

Sulcus implantation of a single-piece foldable acrylic intraocular lens after posterior capsular rupture in cataract surgery.

PURPOSE: To evaluate the safety of a foldable acrylic single-piece intraocular lens (IOL) in cases of complicated cataract surgery and sulcus implantation. The setting was University and private anterior segment surgery practices. METHODS: In this observational case series study, 13 eyes of 13 patients were included after complicated phacoemulsification with extensive posterior capsule rupture with or without vitreous loss. A foldable acrylic single-piece IOL (Rayner Superflex 620H; Rayner Intraocular Lenses Limited, Hove, East Sussex, UK) was implanted in the ciliary sulcus in each eye. Postoperative follow-up included best-corrected visual acuity, anterior segment biomicroscopy, IOL centration and position, intraocular pressure, and fundus biomicroscopy. Optical coherence tomography was performed in 2 subjects. Median follow-up time was 12 months (range 1-21 months). RESULTS: Visual acuity 12 months after surgery was 6/18 and below in 5 eyes (39%), between 6/12 and 6/7.5 in 6 eyes (46%), and 6/6 in 2 eyes (15%). All patients experienced vision improvement. Postoperative complications included corneal edema (2 eyes), Descemet folds (1 eye), intraocular pressure elevations (3 eyes), and pronounced anterior segment inflammation (1 eye). Two eyes had minor pupil contour abnormalities. No significant IOL decentration was observed. CONCLUSIONS: Sulcus implantation of a foldable acrylic single-piece IOL in eyes with complicated cataract surgery maintains the advantages of easy insertion and small incision. Postoperatively, all IOLs were centered, visual results were good, and complications were manageable and not IOL-related.

Efficacy and tolerability of preservative-free eye drops containing a fixed combination of dorzolamide and timolol in glaucoma patients.

PURPOSE: To evaluate the efficacy and tolerability of preservative-free eye drops (dorzolamide/timolol) in routine management of preservative-sensitive glaucoma patients. METHODS: Data from 2,298 glaucoma patients requiring intraocular pressure (IOP) reduction and suffering from intolerance to benzalkonium chloride or active agents of previously used eye drops were valid for baseline and safety analysis in this prospective, open, noncomparative, multicenter, noninterventional study. Patients were treated with preservative-free dorzolamide/timolol eye drops for 12 weeks. Main efficacy endpoint was IOP reduction after 12 weeks of treatment. Two thousand forty-nine patients were considered for efficacy analysis. Tolerability was assessed by evaluating adverse drug reactions. RESULTS: Mean baseline IOP was 20.8 mmHg. Baseline IOP was reduced to 16.7 mmHg after 12 weeks of treatment corresponding to a mean absolute (percent) change of -4.1 mmHg (-17.3%). The proportion of patients with IOP ≤21 mmHg increased from 59.9% at baseline to 94.6% after 12 weeks. The most frequently reported ocular adverse drug reactions were burning eyes (2.4%) and hyperemia (0.9%). Local tolerability improved in 79.3% of patients compared to their previous glaucoma therapy. CONCLUSIONS: This observational study confirms the IOP lowering effect of preservative-free eye drops containing the fixed combination of dorzolamide/timolol in a large patient's population. The drug was well tolerated and improved the local tolerability in the vast majority of patients.

Surface topographies of glaucoma drainage devices and their influence on human tenon fibroblast adhesion.

PURPOSE: This study was performed to investigate the surface topography of different glaucoma drainage devices and to determine the effects of surface roughness on cell adhesion of cultured human tenon fibroblasts. METHODS: The surface topography of four widely used devices (Ahmed FP7 and Ahmed S-2; New World Medical, Inc., Rancho Cucamonga, CA; Baerveldt BG101-350; Advanced Medical Optics, Irvine, CA; and Molteno S1; Molteno Ophthalmic Ltd., Dunedin, New Zealand) was investigated by scanning electron microscopy, and roughness was quantified by white-light confocal microscopy. Cells were grown for 72 hours on the surfaces of implants affixed to standard culture dishes. The cells were labeled with a fluorescent dye and detected by confocal laser scanning microscopy, while simultaneously imaging the surface reflectance. Collagen adsorption was quantified immunologically by using fluorescent beads coupled to a secondary antibody. RESULTS: The root-mean-square roughness was 1.5 +/- 0.1 microm (mean +/- SE) for the silicone Ahmed model FP7 and 1.3 +/- 0.1 microm for the Ahmed with polypropylene base plate Ahmed model S-2. The Baerveldt was substantially smoother, with a mean roughness of 0.1 +/- 0.01 microm. The Molteno was the smoothest of all devices (0.07 +/- 0.01 microm). Cell adhesion was most prevalent on base plates with higher surface roughness, markedly less pronounced on the smoother base plates, and independent of collagen adsorption. CONCLUSIONS: The most frequently implanted glaucoma drainage devices are of markedly different surface topography. Surface roughness appears to correlate with tenon fibroblast adhesion in vitro and also with the rate of occurrence of postimplantation hypertensive phase and failure due to fibrous encapsulation. Surface roughness may thus play a role in triggering excessive fibrovascular reactions. Smoother base plate surfaces may enhance the success rates of these devices.

Subclinical optic neuropathy in Fabry disease.

BACKGROUND: Fabry disease is a rare X-linked lysosomal storage disorder, caused by the deficiency of alpha-galactosidase A. Ophthalmic features comprise a cornea verticillata, conjunctival aneurysms, tortuous conjunctival and/or retinal vessels, and anterior and posterior subcapsular cataracts. The issue of a possible subclinical optic neuropathy in Fabry disease has been raised recently. In this pilot study, we looked for signs of optic neuropathy in our cohort of Fabry patients. METHODS: Thirty-one Fabry patients (15 male, 16 female, mean age 34 years) underwent an ophthalmological investigation consisting of assessment of best corrected visual acuity, slit lamp investigation, testing of pupillary reaction, funduscopy, applanation tonometry, and automated perimetry (Humphrey 30-2). Twenty-nine patients received enzyme replacement therapy with agalsidase alpha (Replagal). RESULTS: Twenty-five of thirty-one patients showed the typical cornea verticillata, tortuous vessels were seen in 17. Two patients exhibited the pathognomonic posterior subcapsular spoke-like ('Fabry') cataract. Intraocular pressure (IOP) was < or = 20 mm Hg in all patients (mean IOP, range 10-20 mm Hg), and all had normal appearing discs on direct funduscopy. Ten out of 31 patients revealed pathological visual fields exhibiting relative central scotomas in automated 30 degrees static perimetry. CONCLUSIONS: In the absence of any other plausible explanation responsible for the field defects detected, we found subclinical optic neuropathy in 10/31 patients suffering from Fabry disease. This figure is in line with a previous report and raises the question whether perimetry should become a part of the ophthalmological examination in Fabry patients. Remarkably, our patients did not complain about any visual impairment. Further investigations are needed to more precisely define this complication of Fabry disease.

Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork.

BACKGROUND: Endothelin-1 (ET-1) is known to induce contraction of trabecular meshwork (TM) and is probably involved in the pathogenesis of glaucoma. Calcium (Ca(2+))-independent contraction has been shown in TM, and its inhibition may represent an interesting way of influencing outflow facility, and thus intraocular pressure (IOP). This study investigates the role of ET-1 and its receptors ET-A and ET-B (ET-AR and ET-BR) in TM Ca(2+)-independent contractility. METHODS: Isometric tension measurements of bovine TM (BTM) strips were performed using a force-length transducer system. Intra- and extracellular Ca(2+) buffering was achieved by means of EGTA and BAPTA-AM. Under Ca(2+)-free conditions, ET-1-induced contractility of TM was assessed also in the presence of the specific inhibitors for ET-AR and ET-BR, BQ123 and BQ788 respectively. In order to clarify the intracellular mediators of Ca(2+)-independent contractility induced by ET-1, TM contraction was further measured in the presence of Y-27632, a selective inhibitor of Rho-associated kinases (ROCKs). The expression of ROCK1 and of its activating protein RhoA in BTM cells was investigated using western blot analysis. RESULTS: ET-1 induced a significant contraction of native BTM after intra- and extracellular Ca(2+)-depletion (45% +/- 8% of the maximally inducible contraction). Both endothelin receptor inhibitors BQ123 and BQ788 significantly reduced TM Ca(2+)-independent contraction in response to ET-1 (8.4 +/- 3.3% and 20.3 +/- 4.8% respectively). In the presence of the ROCK inhibitor Y-27632, ET-1-induced contraction of TM under Ca(2+)-free conditions was almost completely abolished (4.3% +/- 1.7%, p < 0.001). A clear signal for RhoA at 24 kDa and ROCK1 at 160 kDa could be detected in lysates of native tissue and cultured BTM cells with western blot. CONCLUSIONS: This study shows evidence that a significant portion of ET-1-induced contraction of TM is Ca(2+)-independent. In this contraction pathway, both ET-AR and ET-BR are involved with RhoA and its kinases as intracellular mediators. Ca(2+)-independent contraction of TM in response to ET-1 may represent a specific target to modulate IOP.

Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study.

OBJECTIVE: To evaluate the effect of optic nerve circulation, using color Doppler imaging (CDI), on the progression of visual field damage in primary open-angle glaucoma. METHODS: The relationship between the results of retrobulbar CDI, performed shortly after the diagnosis of primary open-angle glaucoma, and the progression of visual field loss for 7 years was evaluated in 44 glaucoma patients. Color Doppler imaging variables in patients with a stable and deteriorating clinical course were compared, and the pattern of increasing risk for different CDI values was analyzed using an additive logistic model. Based on this nonparametric analysis, we arrived at a discriminant CDI value identifying glaucoma patients with a poor prognosis. On the basis of the discriminant value, patients were divided into 2 groups, and the odds ratio of visual field loss for each group was then estimated. RESULTS: Patients with a stable visual field had a higher diastolic velocity and a lower resistivity index in the ophthalmic artery (P<.001 for both) compared with those with a deteriorating visual field during the study. The odds of visual field deterioration in patients with an ophthalmic artery resistivity index of 0.78 or higher was about 6 times that of patients with an ophthalmic artery resistivity index lower than 0.78. CONCLUSION: Color Doppler imaging variables of the ophthalmic artery correlate with the risk of visual field deterioration in patients with primary open-angle glaucoma.

Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma.

The authors considered a group of patients with newly diagnosed primary open-angle glaucoma studying the effects of a 4-week treatment with timolol or dorzolamide on retrobulbar vessels. Ocular hemodynamics were assessed by means of color Doppler imaging of the ophthalmic artery, the temporal short posterior ciliary arteries (SPCAs) and the central retinal artery. For each vessel, systolic and diastolic blood flow velocities were measured, and the resistivity index (RI) was calculated. The only significant result was a reduction of temporal SPCA RI after dorzolamide treatment in comparison with baseline (p = 0.011). In the same group, dorzolamide treatment had a slight and nonsignificant increase in temporal SPCA diastolic velocity. The resistance decrease observed after dorzolamide treatment in the ciliary circulation may be due to the decrease in intraocular pressure or a possible direct vasodilating effect of the drug.