Topical Ocular Therapy Research Articles

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

MYOPIA MANAGEMENT WITH AYURVEDIC OCULAR THERAPEUTICS: A CLINICAL STUDY

An open-label double-arm randomised study was conducted to evaluate the efficacy of Drishtipradavarti Aschyotana (eye drops) with and without Mahatriphaladi ghrita Tarpana (a nourishing topical ocular therapy) in the management of simple myopia. The study was comprised of two groups with twenty subjects each. Group A subjects were administered Drishtipradavarti Aschyotana (eye drops), and subjects of group B were administered Drishtipradavarti Aschyotana and Mahatriphaladi ghrita Tarpana. The total duration of treatment in both groups was restricted to 90 days. Subjects under the age group of 18-25 years with refractive error up to - 6 D were included in the study; out of the 45 subjects registered for the study, 40 completed the treatment. The parameters, namely, visual acuity, clinical refraction, indistinct distant vision, headache and eye strain, were evaluated statistically before and after the treatment along with the axial length and corneal radius of curvature findings to observe if there is any reduction in axial length and corneal curvature, after the treatment. The results showed a statistically highly significant reduction in symptoms (p = < 0.001 and p = < 0.01) and visual acuity (p = < 0.001) and a significant reduction in clinical refraction (p = < 0.05) in both groups. Group B showed comparatively better results. No significant changes were noticed in axial length and corneal radius of curvature values after the treatment (p = > 0.05). The results indicate that this Ayurvedic management can be utilised as a safe and potent treatment to control Myopia.

Differentiating primary dry eye disease from ocular neuropathic pain: implications for symptom management

ABSTRACT Clinical Relevance Eyecare practitioners’ management of ocular surface disease is essential in managing increasing dry eye disease (DED) presentations including ocular neuropathic pain (ONP). Topical Proxymetacaine offers a simple, readily available and practical method of detecting ONP in practice and can be used to differentiate ONP from DED by eyecare practitioners, when accompanied with an anterior segment examination. Background Differentiating DED from ONP presents a significant opportunity to eyecare providers, allowing appropriate treatment choices for more adequate symptom control, greater patient satisfaction, and reduced emergent re-presentations. This study aims to differentiate patients presenting with DED symptoms into DED or ONP using a simple diagnostic tool, which can be used in practice to allocate appropriate treatment options for the patient’s respective condition. A comparison of the prevalence of presentations of ONP presenting with DED symptoms in hospital ophthalmology settings and in optometric primary care settings will also be made. Methods Patients with symptoms of DED were opportunistically recruited as they presented to ophthalmology outpatient clinics and primary care optometric services. Patients were then categorised as DED, ONP, or mixed DED/ONP based on their subjective response 30 seconds post-Proxymetacaine Hydrochloride 2% instillation. Results Twenty-one patients were recruited, including 12 patients from ophthalmologic outpatient clinics and nine patients from primary care optometric services. Twelve patients were identified to have primary DED, while nine patients were identified to have ONP. 43% of patients presenting with DED symptoms had features of neuropathic pain in ophthalmologic outpatient presentations compared to 44% of patients in primary care optometric services. Conclusion Categorising DED and ONP patients by their response to Proxymetacaine can be used as a simple diagnostic tool in guiding future patient management and can be indicative of their potential response to topical therapies. The use of topical Proxymetacaine and the resultant change in ocular pain score can facilitate selection of patients who may benefit from centrally acting neuropathic pain agents over topical ocular therapy.

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU): A Case Series in a Tertiary Care Uveitis Setting.

Background: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disorder typically characterized by sudden-onset non-granulomatous anterior uveitis associated with tubulointerstitial nephritis (TIN). However, the prevalence and clinical features of TINU are still a matter of debate. To add information about TINU, we describe here the clinical features of a series of patients affected by TINU in a retrospective study. Methods: A total of 9358 clinical records of both adult and pediatric patients up to 21 years of age, referred to the Uveitis Center of the Sapienza University of Rome, were examined. The medical records covered a period from 1990 to 2020. Various demographic and clinical features were analyzed in patients who met the criteria for TINU. Results: Twenty-one patients with TINU were identified. TINU was classified as definite, possible, or probable by the currently recognized international criteria. The median age at diagnosis was 14 years (interquartile range 12–35). Females were predominant (15/21, 71.4%). In most cases (14/21, 66.6%), patients developed ocular disease concurrently with renal disease. The most frequent type of ocular involvement was bilateral anterior uveitis (9/21, 42.8%). In two cases, patients presented with bilateral intermediate uveitis; in three cases, they presented with bilateral or unilateral alternating posterior uveitis; and in four cases, they presented with bilateral panuveitis. In one case, the uveitis was anterior in the right eye (OD) and posterior in the left eye (OS), and two cases presented with bilateral asynchronous or unilateral alternating anterior uveitis. All patients received treatment with systemic corticosteroids and topical ocular therapy. At the end of the follow-up, a significant improvement in ocular signs and symptoms with a return to normal visual acuity was generally observed. In all patients, acute kidney injury (AKI) reverted completely and none progressed to chronic kidney disease (CKD). Conclusions: Patients with TINU may often present with atypical uveitis. We suggest that patients with sudden-onset uveitis, even if not bilateral anterior, should be referred to a nephologist for an assessment of the possible presence of renal disease.

Lomefloxacin loaded solid lipid nanoparticles gel for topical ocular therapy: Optimization, evaluation and ex vivo studies

The present study was conducted to develop a novel Lomefloxacin-loaded SLN gel to treat eye infections. Lomefloxacin-loaded solid lipid nanoparticles were prepared by the emulsification solvent evaporation method. Stearic acid was used as solid lipid and poloxamer 188 as surfactant. Optimization of nanoformulation was done by Box Behnken Design using Design Expert Software 12. Stearic acid, poloxamer 188 and propylene glycol concentrations were the independent variables and particle size and % entrapment efficiency (EE) were dependent variables. The optimized lomefloxacin-loaded SLN was further incorporated into Chitosan (LSNG). A total of 9 batches (LSNG1 to LSNG9) were prepared by varying the concentration of Chitosan from 0.05% w/v to 0.25%w/v. LSNG8 was selected as an optimized batch based on its gelling capacity and viscosity. In vitro and ex vivo studies of LSNG8 showed drug release for a prolonged period of time. Furthermore, the HET-CAM test revealed that the formulation is non-irritant and thus can be well tolerated when instilled in the eye. Therefore, LSNG8 can offer improved management of microbial growth.

Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Sorafenib (SRB), a multikinase inhibitor, is effective in reducing experimental corneal neovascularization (CNV) after oral administration; however, its therapeutic use in ocular surface disorders is restricted due to poor solubility and limited bioavailability. This study aimed to develop and optimize SRB-loaded nanostructured lipid carriers (SRB-NLCs) for topical ocular delivery by a central composite design response surface methodology (CCD-RSM). It was spherical and uniform in morphology with an average particle size of 111.87 ± 0.93 nm and a narrow size distribution. The in vitro drug release from the released SRB-NLC formulation was well fitted to Korsmeyer Peppas release kinetics. The cell counting kit-8 (CCK-8) cell viability assay demonstrated that SRB-NLC was not obviously cytotoxic to human corneal epithelial cells (HCECs). An in vivo ocular irritation test showed that SRB-NLC was well tolerated by rabbit eyes. Ocular pharmacokinetics revealed 6.79-fold and 1.24-fold increase in the area under concentration-time curves (AUC0-12h) over 12 h in rabbit cornea and conjunctiva, respectively, treated with one dose of SRB-NLC compared with those treated with SRB suspension. Moreover, SRB-NLC (0.05% SRB) and dexamethasone (0.025%) similarly suppressed corneal neovascularization in mice. In conclusion, the optimized SRB-NLC formulation demonstrated excellent physicochemical properties and good tolerance, sustained release, and enhanced ocular bioavailability. It is safe and potentially effective for the treatment of corneal neovascularization.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Bortezomib-Induced Blepharitis: a Case Report

Introduction: Bortezomib is a proteasome inhibitor approved for the treatment of multiple myeloma, and has known manageable toxicities. Blepharitis is an inflammatory condition of the eyelid that leads to formation of chalazia both causing visual field disturbance. Bortezomib induced blepharitis has not been well reported in the literature. Case: we present a case of 76 year old lady with multiple myeloma who developed bortezomib-induced blepharitis and chalazia. Patient was successfully treated after topical ocular therapy, systemic antibiotherapy and omission of bortezomib.

Rationalized Approach for Formulation and Optimization of Ebastine Microemulsion Using Design Expert for Solubility Enhancement

Ebastine is available as an oral antihistamine formula for allergic disorders such as tablets and syrup. Oral ebastine causes unfavorable effects on heart like QT prolongation, severe gastric distress, decreased tear production, resulting in dryness of the ocular surface, which exacerbates ocular discomfort and increasing susceptibility of eye to irritation. To avoid systemic side effects and ocular discomfort, topical ocular therapy could prove to be superior to systemic therapy in treating ocular allergies. Hence, topical formulation was developed to achieve onsite exposure of ebastine for ocular allergies. Moreover, conjunctiva is more accessible to hydrophilic molecules than lipophilic molecules. This creates challenge for a lipophilic molecule such as ebastine for topical ocular development. Successful dissolution of ebastine in o/w microemulsion allows its use in more convenient soluble form. Initially, solubility of drug in various oils, surfactant and cosurfactant was determined, followed by pseudo-ternary phase diagram to find microemulsion area. The D-optimal mixture design was employed for optimization of formulation. The optimized microemulsion formulation was characterized for its transparency, drug content, droplet size, zeta potential, viscosity, isotonicity, osmolarity and surface tension etc. The optimum physicochemical properties were observed to be eye-fitting. Carboxy methyl cellulose and sodium hyaluronate were used as gelling agents at different concentrations to increase residential time at the site of action. In vitro drug release study revealed that ebastine release from microemulsion gel in a sustained manner up to 24 hrs. for the purpose of providing prolonged therapy for ocular allergy. Hence, prepared microemulsion had great potential as an alternative to customary oral formulations of poorly soluble drug. Keywords: Ebastine, Microemulsion, D-optimal mixture design, Solubility

Nanoemulsion Based Vehicle for Effective Ocular Delivery of Moxifloxacin Using Experimental Design and Pharmacokinetic Study in Rabbits.

Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor® P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1–MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1–MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm2/h) and control (~31.53 µg/cm2/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (Cmax; 555.73 ± 133.34 ng/mL) and delayed Tmax value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (AUC0–8 h) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy.

Preparation and Evaluation of Topically Applied Azithromycin Based on Sodium Hyaluronate in Treatment of Conjunctivitis.

Azithromycin (AZI) eye drops containing sodium hyaluronate (SH) were developed to improve the bioavailability of AZI. Interaction between AZI and SH in the AZI-SH formulation was investigated by differential scanning calorimetry, X-ray diffraction, and 1H-nuclear magnetic resonance spectroscopy analyses. Moreover, advantages of using SH as an excipient were investigated by comparing physiological properties and pharmacokinetic behaviors of SH-containing AZI eye drops with that of hydroxypropyl methylcellulose (HPMC)-containing formulation. In addition, safety of the developed AZI-SH eye drops was evaluated by in vitro 3-(4,5-dimethyl-2-Thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay (MTT assay) and neutral red uptake assay as well as in vivo eye irritation test and acute toxicity test. The results indicated that AZI formed a complex with SH under a slightly acidic condition. The area under the curve (AUC) of AZI in SH-containing formulation was 1.58-fold higher (P < 0.01) than that in HPMC-containing formulation due to the interaction between the amine group of AZI and the carboxyl group of SH, despite of the higher viscosity of HPMC-containing formulation. Safety evaluation showed that AZI-SH eye drops caused no obvious eye irritation and acute toxicity. In conclusion, the developed SH-containing AZI formulation possessing advantages of longer retention time and higher drug availability was a promising drug formulation for topical ocular therapy.

The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration.

A noninvasive topical ocular therapy for the treatment of neovascular or "wet" age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAR related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small-molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile.

Nanogels of methylcellulose hydrophobized with N-tert-butylacrylamide for ocular drug delivery.

While eye drops account for the majority of ophthalmic formulation for drug delivery, their efficiency is limited by rapid pre-corneal loss. In this study, we investigate nanogel suspensions in order to improve the topical ocular therapy by reducing dosage and frequency of administration. We synthesized self-assembling nanogels of 140nm by grafting side chains of poly(N-tert-butylacrylamide) (PNtBAm) on methylcellulose via cerium ammonium nitrate. Successful grafting of PNtBAm onto methylcellulose (MC) was confirmed by both NMR and ATR. Synthesized molecules (MC-g-PNtBAm) self-assembled in water driven by hydrophobic interaction of the grafted side chains creating colloid solutions. Materials were synthesized by changing feed ratios of acid, initiator and monomer in order to control the degree of hydrophobic modification. The nanogels were tested for different degrees of grafting. Viability studies performed with HCE cells testified to the biocompatibility of poly(N-tert-butylacrylamide) grafted methylcellulose nanogels. Dexamethasone was entrapped with an efficiency superior to 95% and its release presented minimal burst phase. Diffusion of drug from the nanogels was found to be delayed by increasing the degree of grafting. The release profile of the entrapped compound from the MC-g-PNtBAm nanogels can thus be tuned by simply adjusting the degree of hydrophobic modification. MC-g-PNtBAm nanogels present promising properties for ocular drug delivery.

Preliminary characterization of dexamethasone-loaded cross-linked hyaluronic acid films for topical ocular therapy

The aim of this work was to design and characterize cross-linked hyaluronic acid (HA)–itaconic acid (IT) films loaded with dexamethasone sodium phosphate salt (DEX) for topical therapy of inflammatory ocular surface diseases. Films were chemically cross-linked with polyethylene glycol diglycidyl ether (PEGDE), then physical and mechanical characterization by stress–strain, X-ray diffraction, X-ray fluorescence spectrometry and swelling assays was conducted. A sequential in vitro therapeutic efficacy model was designed to assess changes in interleukin (IL)-6 production in an inflamed human corneal epithelial (HCE) cell line after film exposure. Changes in cell proliferation after film exposure were assessed using the alamarBlue® proliferation assay. Experimental findings showed desirable mechanical properties and in vitro efficacy to reduce cell inflammation. A moderately decreased proliferation rate was induced in HCE cells by DEX-loaded films, compared to commercial DEX eye drops. These results suggest that DEX and HA have opposite effects. The sequential in vitro therapeutic efficacy model arises as an efficient tool to study drug release from delivery systems by indirect measurement of a biological response.

Sinais e sintomas de doença da superfície ocular em usuários de hipotensores oculares tópicos

To determine the prevalence of signs and symptoms of ocular surface disease (OSD) in patients using topical intraocular pressure-lowering therapy. In this cross-sectional study, 40 patients were consecutively recruited from the glaucoma clinic of a public hospital located in Rio de Janeiro, Brazil. Eligible patients were 18 years of age or older, with primary open-angle glaucoma or ocular hypertension and on the same topical ocular therapy for at least 6 months. The following data were considered: sex, age, medication history and number of years on topical intraocular pressure-lowering therapy. All patients underwent an evaluation of the ocular surface which included: an interview using the Ocular Surface Disease Index® (OSDI®) questionnaire, break-up time, biomicroscopy, fluorescein corneal staining and rose Bengal ocular surface staining. The mean OSDI® score was 24.6 ± 20.7. Most patients (67.5%) had an abnormal score on the OSDI® questionnaire. In 25% of patients, the score was consistent with mild symptoms, 12.5% with moderate symptoms and 30% with severe symptoms. Blepharitis and punctate keratitis were diagnosed in 42.5% and 20% of patients respectively. Tear film instability was observed in 75% of patients and ocular surface staining with rose Bengal in 35%. A positive statistically significant correlation (r=0.4; p=0.01) was found between OSDI® scores and the duration of topical intraocular pressure-lowering therapy. Patients with primary open-angle glaucoma or ocular hypertension on topical intraocular pressure-lowering therapy have high prevalence of OSD. Longer duration since diagnosis is significantly correlated with worsening of OSD symptoms.

Ocular biocompatibility of novel Cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers

Topical ocular drug delivery has always been a challenge for pharmaceutical technology scientists. In the last two decades, many nano-systems have been studied to find ways to overcome the typical problems of topical ocular therapy, such as difficult corneal penetration and poor drug availability. In this study, methoxy poly(ethylene glycol)-hexylsubstituted poly(lactides) (MPEG-hexPLA) micelle formulations, which are promising nanocarriers for poorly water soluble drugs, were investigated for the delivery of Cyclosporin A (CsA) to the eye. As a new possible pharmaceutical excipient, the ocular compatibility of MPEG-hexPLA micelle formulations was evaluated. An in vitro biocompatibility assessment on human corneal epithelial cells was carried out using different tests. Cytotoxicity was studied by using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), and clonogenic tests and revealed that the CsA formulations and copolymer solutions were not toxic. After incubation with MPEG-hexPLA micelle formulations, the activation of caspase-dependent and -independent apoptosis as well as autophagy was evaluated using immunohistochemistry by analyzing the localization of four antibodies: (1) anti-caspase 3; (2) anti-apoptotic inducing factor (AIF); (3) anti-IL-Dnase II and (4) anti-microtubule-associated protein 1 light chain 3 (LC3). No apoptosis was induced when the cells were treated with the micelle solutions that were either unloaded or loaded with CsA. The ocular tolerance was assessed in vivo on rabbit eyes by Confocal Laser Scanning Ophthalmoscopy (CLSO), and very good tolerability was seen. The observed corneal surface was comparable to a control surface that was treated with a 0.9% NaCl solution. In conclusion, these results demonstrate that MPEG-hexPLA micelles are promising drug carriers for ocular diseases involving the activation of cytokines, such as dry eye syndrome and autoimmune uveitis, or for the prevention of corneal graft rejection.

Adherence with brimonidine in patients with glaucoma aware and not aware of electronic monitoring

To assess the impact of open versus masked adherence monitoring on adherence with topical brimonidine using two different dosing schedules. Thirty-seven patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Patients were randomly assigned to open or masked adherence monitoring and to brimonidine twice daily (BID) or three times daily (TID). Patients received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks with weekly intraocular pressure measurements. Adherence calculations comprised dosing intervals, adherence rate and time covered. Subgroup analysis with anova included the factors masking, regimen, diagnosis and age. Among 36 individually analysed patients, 12 (33%) had adherence rates above 75%, therein two (5%)>90%. The mean adherence rate in 19 patients aware of adherence measurements was 70 ± 17% for brimonidine BID and 65 ± 14% for TID, not significantly different to the rates of 17 patients not informed about adherence measurements (77 ± 6% BID, 62 ± 9% TID, p = 0.24). On average, patients with brimonidine TID achieved significantly lower adherence rates (64 ± 12%) than patients on BID (73 ± 13%, p = 0.02). Still, patients on TID applied brimonidine more often (TID 1.9 ± 0.3, BID 1.5 ± 0.1 mean applications per day). The median coverage was 70% and showed no statistically significant difference between patients on BID and TID (p = 0.36). The study findings suggest that adherence measurements are not significantly altered by open adherence monitoring, which may simplify future adherence studies. Adherence with brimonidine eye drops was insufficient for most patients. These results demonstrate the necessity to develop new strategies to improve compliance in glaucoma therapy.

Electronic compliance monitoring in glaucoma patients used to topical therapy

Abstract Purpose Individual compliance of glaucoma and ocular hypertensive patients with Brimonidine was studied with regards to total dose, dosage intervals, coverage, drug waste, attempts per application and risk factors for low compliance. Methods Thirty‐eight men and 26women aged 70 ±11 years [42‐89] received conventional Brimonidine vials (Alphagan®, Allergan™) equipped with a microprocessor‐controlled monitoring device capable to record date and time of each eye drop application with a known detection sensitivity for eye drop applications ~ 99%. 48 glaucoma and 16 ocular hypertensive patients used to eye drop therapy for 11 ±8 years [1‐35] were enrolled and randomly assigned to Brimonidine therapy b.i.d or t.i.d daily for 4 weeks. Results Electronic records revealed a mean of 1.4 applications per day (range: 0.7‐2.2) for patients assigned to Brimonidine 2x daily with a mean treatment interval of 18.2 hours (range: 11.2‐38.4 h). Patients on Brimonidine 3x daily showed a mean rate of 1.8 applications per day (range: 1.0‐2.7) and a mean treatment interval of 12.4 h (range: 9.1‐39.7 h). 10 patients ceased therapy before completing the 4 weeks period, therein 4 with side effects and 6 patients having emptied the bottle prematurely. Conclusion Almost 10 percent of the patients emptied their vial in less than 4 weeks by using more than one drop per application and thereby do need refills more often than usually calculated. Our data confirm the need for larger studies on individual compliance with topical ocular therapy in glaucoma. Electronic compliance monitoring may be a useful tool in ophthalmic practice to recognize low‐compliant patients.

Risk Factors for Scleral Buckle Removal: A Matched, Case-Control Study

To identify preoperative, perioperative, and postoperative risk factors for scleral buckle (SB) removal. Retrospective, consecutive, matched, case-control study. Cases included all patients undergoing SB removal between August 1988 and December 2007 at a single academic center. Cases were matched against four randomly selected control patients who underwent SB implantation during the same year as the case. Odds ratios (OR) were calculated for each factor investigated. Forty cases of SB removal and 148 matched control cases were identified. Three cases of SB removal were omitted from analysis because of incomplete records. Factors associated with SB removal for any reason, using univariate analysis, included concurrent globe-penetrating injury at time of SB placement (OR, 24; 95% confidence interval [CI], 2.9 to 200), concurrent pars plana vitrectomy (PPV) (OR, 17.3; 95% CI, 4.9 to 61), diabetes mellitus (DM) (OR, 7.3; 95% CI, 1.8 to 30), prior chronic topical ocular therapy (OR, 4.3; 95% CI, 1.7 to 11), and subsequent ocular procedures (OR, 3.4; 95% CI, 1.5 to 7.5). Factors independently associated with SB removal using multivariate analysis included concurrent globe-penetrating injury (OR, 27.3; 95% CI, 1.7 to 426), concurrent PPV (OR, 11.3; 95% CI, 2.9 to 45), DM (OR, 8.9; 95% CI, 1.3 to 58), and subsequent ocular procedures (OR, 3.9; 95% CI, 1.4 to 11). Factors that did not alter SB removal risk included patient age; gender; and type, size, or location of buckling elements used. Awareness of these risk factors may be valuable for the surgical planning of retinal detachment repair in patients at higher risk for subsequent SB removal and for risk stratification subsequent to SB implantation.

Monitoring individual compliance in glaucoma patients used to topical therapy

Abstract Purpose: Individual compliance with Brimonidine eye drops was studied in glaucoma patients and ocular hypertensives. Methods: Conventional Brimonidine vials were equipped with a microprocessor‐controlled monitoring device capable to record date and time of each eye drop application including ambient temperature. After written informed consent, glaucoma and ocular hypertensive patients used to eye drop therapy were randomly assigned to Brimonidine therapy b.i.d or t.i.d daily for 4 weeks. Results: Twenty six males and fourteen females aged 69 ± 11 years [42‐89] were enrolled in this study. According to the monitoring devices all patients were non‐compliant with regard to total dose and coverage. Electronic records revealed a mean of 1.5 (range: 1.1‐2.0) applications per day for patients assigned to Brimonidine 2x daily with a mean treatment interval of 16.8 hours (range: 12.1‐22.2 h). Patients on Brimonidine 3x daily showed a mean rate of 1.9 (range: 1.8‐2.7) applications per day and a mean treatment interval of 11.9 h (range: 9.1‐13.9 h). One patient discontinued therapy after day 7 (12 applications) and one after day 1 (1 application only). No difference was observed between IOP at baseline and after one month (p=0.16). Conclusions: The monitoring devices permit to detect individual non‐compliance with regard to missed doses, non‐treatment intervals. Our data confirm the need for larger studies on individual compliance with topical ocular therapy in glaucoma.