Journal of Ocular Pharmacology and Therapeutics (J OCUL PHARMACOL TH )

Publisher: Society for Ocular Pharmacology and Therapeutics, Mary Ann Liebert

Description

This peer-reviewed journal publishes research on all aspects of drug activity pertaining to preventing or controlling diseases of the eye. The official journal of the Society for Ocular Pharmacology and Therapeutics.

Impact factor 1.42

  • Hide impact factor history
     
    Impact factor
  • 5-year impact
    1.32
  • Cited half-life
    6.20
  • Immediacy index
    0.14
  • Eigenfactor
    0.00
  • Article influence
    0.36
  • Website
    Journal of Ocular Pharmacology and Therapeutics website
  • Other titles
    Journal of ocular pharmacology and therapeutics (Online), Journal of ocular pharmacology and therapeutics
  • ISSN
    1080-7683
  • OCLC
    47295624
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Mary Ann Liebert

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's final version or publisher's version/PDF
    • Publisher's version/PDF may be used
    • On author's personal website, institution's intranet, or institutional repository
    • Authors may deposit in funder's designated repository after 12 months
    • Set statement to accompany deposit (see policy)
    • Publisher copyright and source must be acknowledged
    • NIH authors will have their final paper, (post peer review, copy-editing and proof-reading) deposited in PubMed Central on their behalf
  • Classification
    ​ blue

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To compare loteprednol etabonate 0.5%/tobramycin 0.3% (Zylet(®)) with dexamethasone 0.1%/tobramycin 0.3% (Tobradex(®)) in terms of the epithelial healing time, postoperative visual acuity, corneal haziness score, and intraocular pressure (IOP) in postoperative treatment after photorefractive keratectomy (PRK). Methods: This prospective, randomized, double-masked (participants and assessors blinded) controlled study included 32 patients who underwent PRK. The patients were allocated equally into 2 groups by block randomization to receive either loteprednol etabonate (Lot) or dexamethasone (Dex) for 1 month after the surgery. The epithelial healing time, uncorrected visual acuity (UCVA), corneal haziness score, and IOP were evaluated at 1 week, 1 month, and 3 months. Results: The corneal epithelium was healed within 3 days in both groups; however, the epithelium was closed on the second day in 3 cases in the Lot group compared with 1 case in the Dex group. No significant differences were found for UCVA at 1 and 3 months (Fisher exact test, P>0.01). Similarly, there was no statistically significant difference in corneal haziness scores between the 2 groups at 1 and 3 months (Mann-Whitney U test, P>0.05). The number of patients experiencing significantly increased IOP (≥5 mmHg) from baseline at any visit for the Lot group (1/16 patients) was fewer than for the Dex group (3/16 patients). Conclusions: Loteprednol etabonate was effective in postoperative PRK management and was significantly less likely to produce elevations in IOP than was dexamethasone.
    Journal of Ocular Pharmacology and Therapeutics 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: Senescence of the retinal pigment epithelial (RPE) cell layer has been implicated in the occurrence of age-related macular degeneration (AMD). The present study examines whether the ability of vascular endothelial growth factor (VEGF) to decrease the barrier function of RPE cells is enhanced in senescent RPE cells, which could contribute to the pathology of "wet" AMD. Methods: Low or high population doubling level (PDL) range ARPE-19 human RPE cells were cultured in 6-well plates on membrane-containing inserts. After 2 weeks, the cells were treated with either VEGF or its vehicle and their transepithelial electrical resistance (TEER) was measured. One week later, the cells were stained for senescence-associated β-galactosidase (SABG) activity. Results: VEGF was significantly more effective in reducing the TEER of the high PDL ARPE-19 cell layers than the low PDL layers (25% decrease vs. 6% decrease; t-test, P=0.0013). The low PDL cell layers had a modest uniform level of SABG staining. In contrast, the high PDL layers displayed darker and more mottled SABG staining indicative of the presence of senescent cells. Conclusions: The present results show that the ability of VEGF to reduce the barrier function of RPE cell layers is greater in high PDL layers, which display signs of senescence, than in low PDL layers. Senescence-induced changes in the responsiveness of RPE cell layers to VEGF could contribute to the pathology of AMD. Agents that strengthen the barrier properties of RPE cells or reduce their responsiveness to VEGF could be effective in treating "wet" AMD.
    Journal of Ocular Pharmacology and Therapeutics 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: Dexamethasone intravitreal implant (DEX implant, Ozurdex(®); Allergan, Inc.) is used to treat noninfectious posterior uveitis and macular edema associated with retinal vein occlusion and diabetic retinopathy. Two recently published reports of DEX implant fragmentation shortly after injection have raised concerns about the potential for faster implant dissolution and elevated ocular dexamethasone concentrations. This study compared the in vivo release profile and pharmacokinetic behavior of intact and fragmented DEX implants. Methods: DEX implant was surgically implanted as a single unit or fragmented into 3 pieces in the posterior segment of opposing eyes of 36 New Zealand white rabbits. The release of dexamethasone over time from 1-piece and 3-piece fragmented implants dissolved in solution in vitro was compared with that from the 1-piece and 3-piece fragmented implants placed in the rabbit eyes. In addition, dexamethasone concentrations in the vitreous and aqueous humors of each eye were measured at 3 h and days 1, 7, 14, 21, and 28. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used for assays. Results: Dexamethasone release from the 1-piece and 3-piece DEX implants in vivo was not different and was consistent with the in vitro release pattern. Moreover, the concentration profile of dexamethasone in the vitreous and aqueous humors was similar for the 1-piece and 3-piece DEX implants at each time point measured. Conclusions: DEX implant fragmentation neither accelerated its dissolution nor increased the dexamethasone concentration delivered at a given time. Accordingly, DEX implant fragmentation is unlikely to have clinically significant effects in patients.
    Journal of Ocular Pharmacology and Therapeutics 11/2014; 30(10).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: The objective of this study was to collect and evaluate retrospective safety information about the use of besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial keratitis. Methods: This was a retrospective, postmarketing surveillance study conducted at 10 clinical centers in the United States. The study population included 142 patients treated with besifloxacin ophthalmic suspension 0.6% for bacterial keratitis in one or both eyes. For perspective, data on 85 patients treated at these centers with moxifloxacin ophthalmic solution 0.5% for bacterial keratitis were also included. The analysis was designed to measure the types and rates of adverse events (AEs) reported during the treatment of bacterial keratitis with besifloxacin ophthalmic suspension 0.6%. Other treatment outcomes of interest included the development of corneal scarring and corneal neovascularization, measured or presumed bacterial eradication, ending visual acuity, and duration of pain before and after treatment. Results: There was one reported AE of mild superficial punctate keratitis in a patient using besifloxacin ophthalmic suspension 0.6%. The difference in AE frequencies between groups was not significant (P>0.999). Additional treatment outcomes were similar for both groups. Limitations of this report include the retrospective nature of the study. Conclusions: These retrospective data suggest that besifloxacin ophthalmic suspension 0.6% was well tolerated when included in the treatment of bacterial keratitis; no serious AEs were reported. A prospective clinical trial is needed to better isolate the contribution of besifloxacin to the therapeutic outcome and to confirm these observations.
    Journal of Ocular Pharmacology and Therapeutics 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The nitric oxide (NO) pathway and its physiological significance on relaxing smooth muscle and endothelial cells throughout the body is well outlined and understood. Components of this pathway have been located in the ocular anterior and posterior chambers, and they have been connected with vascular, retinal, and trabecular meshwork normal physiology. Nitric oxide has been shown to increase anterior chamber aqueous outflow via reduction in trabeculocyte size and smooth muscle contractility, and Schlemm's canal vasodilation. Anti-vascular endothelial growth factor (VEGF) therapy has been shown to disrupt the normal nitric oxide signaling pathway, producing systemic arterial hypertension following systemically administered anti-VEGF in oncology by exactly that mechanism. Intravitreal anti-VEGF therapy is now considered a standard of care in several retinal diseases. Sustained elevated intraocular pressure (IOP) has been described as a potential adverse effect of therapy that appears related to the number of injections, and it can be produced by any of the various anti-VEGF compounds. We propose a novel mechanism responsible for the increase in IOPs following prolonged intravitreal anti-VEGF therapy. This mechanism postulates a rise in IOP due to a decrease in aqueous outflow from relatively decreased levels of available nitric oxide in the anterior chamber because of anti-VEGF inhibition of nitric oxide synthase. This article outlines the novel mechanism, which provides a likely explanation for this consequence, along with offering therapeutic targets for future research and treatment.
    Journal of Ocular Pharmacology and Therapeutics 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: The aim of the study was to evaluate the effect of 3 subconjunctival bevacizumab injections in patients with an early corneal pterygium recurrence. Methods: This study was a nonrandomized single center trial. Patients with an early corneal pterygium recurrence were selected. All patients received 3 subconjunctival bevacizumab (2.5 mg/0.1 mL) injections (basal, 2 and 4 weeks) in the recurrence area of the pterygium. The corneal and corneal-conjunctival neovascularization areas and the corneal opacification area of each pterygium were determined using digital slit lamp pictures. Results: Thirty-eight patients were enrolled into the study; all patients were injected within 3 months of the diagnosed pterygium recurrence. Interestingly, the bevacizumab injections had a significant effect (P<0.05) on the reduction of corneal, corneal-conjunctival area of neovascularization determined as pixels and on the corneal opacification area determined as mm(2) when comparing the basal values, to the values obtained after 15 days, 1 month, 3 months, 6 months, and 12 months after injections. Conclusions: The vascularized area in all recurrent pterygia and the corneal opacification area with this triple regimen of subconjunctival bevacizumab injections were reduced, which remained until the end of the study. These results suggest that bevacizumab subconjunctival injections could be useful to treat recurrent pterygium.
    Journal of Ocular Pharmacology and Therapeutics 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: We aimed to investigate the safety, tolerability, and systemic diffusion of a single escalating dose of XG-102 (a 31-D-amino-acid peptide inhibiting JNK pathway activation), administered subconjunctivally in the treatment of post-surgery or post-trauma intraocular inflammation. Methods: This is a dose-escalating, tolerance Phase Ib study. Twenty patients with post-surgery or post-traumatic intraocular inflammation were assigned to 1 of the 4 dose escalating (45, 90, 450, or 900 μg XG-102) groups of 5 patients each. Patients were evaluated at 24, 48 h, 8, and 28 days following the administration of XG-102, including laboratory tests, standard eye examinations, vital signs, and occurrence of adverse events. A single plasma quantification of XG-102 was performed 30 min after administration, according to previous pharmacokinetics studies performed on volunteers. Results: A total of 17 non-serious adverse events, considered unrelated to the study treatment, were reported for 10 patients. The adverse event incidence was not related to the drug dose. All patients experienced a decrease in intraocular inflammation as of 24 h post-administration and this decrease was sustained up to 28 days thereafter. No patient required local injection or systemic administration of corticoids following the administration of XG-102. XG-102 was undetectable in the first 3 dose groups. In the fourth-dose group (900 μg) the XG-102 plasma levels were above the limit of detection for 3 patients and above the limit of quantification for 1 patient. Conclusions: In this first clinical trial using XG-102, administered as a single subconjunctival injection as adjunct therapy, in patients with recent post-surgery or post-trauma intraocular inflammation is safe and well tolerated. Further studies are required to evaluate its efficacy.
    Journal of Ocular Pharmacology and Therapeutics 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: The aim of the present study was to evaluate the effectiveness of topically applied tigecycline for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. Methods: Experimental bacterial keratitis was induced in rabbits by a corneal intrastromal injection of 100 colony-forming units (CFUs) of MRSA bacteria. Sixteen hours after the injection, 28 rabbits were randomly divided into 4 treatment groups of 7 rabbits each. In each group, the rabbits' eyes were treated topically with 19 doses of topical tigecycline (10 or 50 mg/mL), vancomycin (50 mg/mL), or isotonic saline. Slit lamp examinations were performed before and after the inoculation by two observers masked to the study for the determination of clinical severity. Corneas were harvested for bacterial quantitation and histopathologic examination. Results: No significant differences were observed in the clinical scores between pretreatment and posttreatment in the 4 groups (P>0.05). The mean difference between the pretreatment and posttreatment clinical scores from the 4 treatment groups was also not significant (P>0.05). All treatment groups had significantly lower CFUs compared with the control group. There were no significant differences in the bacterial load among the treatment groups. The minimum inhibitory concentration (MIC) for tigecycline was 0.12 μg/mL, whereas the MIC for vancomycin was 2.2 μg/mL. The tigecycline 10 mg/mL group had the lowest mean epithelial erosion values among the treatment groups. Conclusions: Topical tigecycline significantly reduced the bacterial load in infected rabbit corneas and may be as effective as vancomycin for the topical treatment of MRSA keratitis.
    Journal of Ocular Pharmacology and Therapeutics 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: XG-102, a TAT-coupled dextrogyre peptide inhibiting the c-Jun N-terminal kinase, was shown efficient in the treatment of experimental uveitis. Preclinical studies are now performed to determine optimal XG-102 dose and route of administration in endotoxin-induced uveitis (EIU) in rats with the purpose of clinical study design. Methods: EIU was induced in Lewis rats by lipopolysaccharides (LPS) injection. XG-102 was administered at the time of LPS challenge by intravenous (IV; 3.2, 35 or 355 μg/injection), intravitreal (IVT; 0.08, 0.2 or 2.2 μg/eye), or subconjunctival (SCJ; 0.2, 1.8 or 22 μg/eye) routes. Controls received either the vehicle (saline) or dexamethasone phosphate injections. Efficacy was assessed by clinical scoring, infiltrating cells count, and expression of inflammatory mediators [inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant-1 (CINC-1)]. The effect of XG-102 on phosphorylation of c-Jun was evaluated by Western blot. Results: XG-102 demonstrated a dose-dependent anti-inflammatory effect in EIU after IV and SCJ administrations. Respective doses of 35 and 1.8 μg were efficient as compared with the vehicle-injected controls, but only the highest doses, respectively 355 and 22 μg, were as efficient as dexamethasone phosphate. After IVT injections, the anti-inflammatory effect of XG-102 was clinically evaluated similar to the corticoid's effect with all the tested doses. Regardless of the administration route, the lowest efficient doses of XG-102 significantly decreased the ration of phospho c-Jun/total c-Jun, reduced cells infiltration in the treated eyes, and significantly downregulated iNOS and CINC-1 expression in the retina. Conclusion: These results confirm that XG-102 peptide has potential for treating intraocular inflammation. SCJ injection appears as a good compromise to provide a therapeutic effect while limiting side effects.
    Journal of Ocular Pharmacology and Therapeutics 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To prospectively evaluate the effects of intravitreal bevacizumab (IVB, Avastin; Genentech, Inc., San Francisco, CA) injections in patients with acute central/hemicentral retinal vein occlusions (C/HCRVOs) (≤1 month after the occlusion was diagnosed) over the course of 3 years. Methods: The study included 57 patients with unilateral acute C/HCRVOs. Initially, the treatment for acute C/HCRVO patients consisted of 4 consecutive IVB injections administered off-label at a dose of 2.5 mg per injection, with each injection spaced ∼45 days apart. Thereafter, IVB therapy was flexible, and subsequent injections were administered during scheduled visits whenever a best corrected visual acuity (BCVA) loss of ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters occurred and/or iris/angle neovascularization appeared (regardless of the intraocular pressure level). Changes in the BCVA and foveal thickness (FT), number of IVB injections administered, and incidence of neovascular glaucoma (NVG) were estimated. Results: The increase in the BCVA score at month 36 was 17.15 (ETDRS letters) (P<0.0001) in cases of nonischemic and 26.81 (ETDRS letters) (P<0.01) in cases of ischemic occlusions. At the end of the follow-up, the proportion of BCVA score improvements greater than 15 ETDRS letters was similar in patients with both forms of occlusions (measured in 45.5% of nonischemic and 45.8% of ischemic patients) (P=0.977). There were significant reductions in FT from baseline values to 230±40.50 μm (P=0.0001) in patients with nonischemic occlusions and 270±40.50 μm (P=0.0001) in patients with ischemic forms. There was a significant difference (P<0.03) in the number of IVB injections administered in patients with nonischemic C/HCRVOs (8.7±1.58) compared to patients with ischemic occlusions (9.7±1.78). NVG occurred in 2 cases of ischemic occlusions. Conclusions: The 3-year IVB therapy provided sustained vision and FT gains in most phakic patients with acute C/HCRVOs, making this treatment option a rational and viable therapeutic strategy. Bevacizumab was more effective in patients with ischemic occlusions who required a significantly higher number of injections.
    Journal of Ocular Pharmacology and Therapeutics 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objective: The purpose of this experiment was to investigate the possible toxic effects of Nepafenac, a nonsteroidal anti-inflammatory molecule, after its intravitreal application in various concentrations. Methods: Forty pigmented rabbits were randomly divided into 4 groups, each including 10 rabbits. The active ingredient Nepafenac was prepared to be applied in different doses, for intravitreal use. Under topical anesthesia, following pupil dilatation, 0.3, 0.5, 0.75, and 1.5 mg doses of Nepafenac was applied intravitreally into the right eye. In each rabbit, the right eye was considered to be the study group. Saline was injected intravitreally into the left eye of each rabbit, and these eyes were considered to be the control group. Immediately after the injection and at the 1st, 4th, and 8th weeks, fundus examination by indirect ophthalmoscopy and intraocular pressure measurement were conducted. Furthermore, electroretinographic (ERG) recordings were taken at the 4th and 8th weeks. At the end of the 8th week, eyes of the surviving 26 rabbits were enucleated, and then animals were sacrificed. Following necessary fixation procedures, histopathological investigations were conducted by using a light and electron microscope. In the histological cross sections, differences between the eyes with injection and the control group were evaluated, and total retinal thickness, inner nuclear layer thickness, and outer nuclear layer thickness were measured. Results: No pathology was found by clinical examination of either group. In the photopic and scotopic full-field ERG, conducted before the injection and in the 4th and 8th weeks after the injection, no statistically significant difference was determined between the study group and the control group. In the histological evaluation of the preparations, there were no statistically significant differences in the retina thickness of control and study groups. In the electron microscopic examinations, there were no toxicity findings in the eyes with injection. Conclusions: Our data show that intravitreal application of 0.3, 0.5, 0.75, and 1.5 mg doses of Nepafenac active substance is nontoxic to the rabbit retina.
    Journal of Ocular Pharmacology and Therapeutics 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To compare the 24-h changes of intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) obtained with tafluprost versus travoprost in patients with normal-tension glaucoma (NTG). Methods: This study is a randomized crossover study of 50 patients newly diagnosed with NTG who received either tafluprost or travoprost given once at 9 PM for 2 months, after which they were crossed over to the other medication for another 2 months. IOP and blood pressure were measured for 24 h before starting the treatment and after finishing the first and second treatment periods. Results: Forty-one patients completed the study. The mean (±standard deviation) 24-h IOP was 16.8±2.0 mmHg at baseline, 14.4±2.2 mmHg on tafluprost, and 13.6±1.8 mmHg on travoprost. Both prostaglandin monotherapies significantly reduced mean 24-h IOP as compared with baseline (P<0.001, P<0.001, respectively), and travoprost demonstrated a lower mean 24-h IOP than tafluprost (P=0.044). Both treatments significantly reduced the IOP from baseline at every point over 24 h. At 3 individual time points, travoprost provided a lower IOP than tafluprost: at 4 PM (13.8±2.7 vs. 14.8±2.6 mmHg, P=0.041), at 6 PM (13.5±2.5 vs. 14.4±2.5 mmHg, P=0.006), and at 8 PM (13.3±2.5 vs. 14.5±2.4 mmHg, P=0.029). Both tafluprost and travoprost significantly increased the 24-h MOPP (P=0.008, P=0.002, respectively), and travoprost demonstrated a greater 24-h MOPP than tafluprost (P=0.027). Conclusions: Both tafluprost and travoprost were effective in lowering IOP and increasing MOPP throughout 24 h in NTG. However, travoprost reduced IOP greater than tafluprost in the late afternoon and evening.
    Journal of Ocular Pharmacology and Therapeutics 10/2014; 30(10).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: Prolonged use of topical antifungal agents may compromise corneal epithelial integrity. Here, we used an in vitro model of human stratified corneal epithelium to compare the ocular toxicity profiles of 4 different antifungal eye drops. Methods: Human corneal epithelial cell sheets were cultured in a serum-free medium containing 0.1% micafungin, 1% voriconazole, 5% pimaricin, 0.1% amphotericin B, or controls (saline or 5% glucose). Cell viability and barrier function were measured by WST-1 assay and carboxyfluorescein permeability assay, respectively. Cell migration was measured on a wound healing assay. Results: WST-1 assay and carboxyfluorescein permeability assay revealed that amphotericin B was the most toxic drug, followed by pimaricin, micafungin, and voriconazole. Cell migration on a wound healing assay was decreased in the following order, amphotericin B, pimaricin, micafungin, and voriconazole. Conclusions: Topical micafungin and voriconazole appeared to be the least toxic to the corneal epithelium. Drug prescription should consider not only fungal species and susceptibility but also ocular toxicity and stage of treatment.
    Journal of Ocular Pharmacology and Therapeutics 10/2014; 30(10).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To investigate the effect of topical motesanib, an inhibitor of receptor tyrosine kinase, on experimental choroidal neovascularization (CNV). Methods: CNV was induced in 46 nine-week-old male C57BL/6 mice using fundus laser photocoagulation. The right eye of each mouse was treated with motesanib eye drop (4 times daily) and the left eye with vehicle eye drop (4 times daily) for 14 days. To evaluate changes in the CNV lesions, fluorescein angiography, immunofluorescence staining with CD34, and histological examinations were performed 14 days after CNV induction. The expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) in choroidal tissues was determined using western blot analysis to demonstrate the inhibitory effect of topically administered motesanib on intracellular signaling pathways involved in CNV development. Results: Fluorescein angiography showed that fluorescence leakage in eyes treated with topical motesanib was significantly less than in mice treated with vehicle (P=0.01). On immunofluorescence staining, the CD34-labeled area was smaller in topical motesanib-treated eyes (P<0.001). The expression level of phosphorylated ERK1/2 relative to that of total ERK1/2 decreased in eyes treated with topical motesanib compared with eyes treated with vehicle. Conclusion: Topical motesanib significantly reduced laser-induced CNV in the experimental mouse model.
    Journal of Ocular Pharmacology and Therapeutics 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Microbial pathogens-bacteria, viruses, fungi, and parasites-are significant causes of blindness, particularly in developing countries. For bacterial and some viral infections a number of antimicrobial drugs are available for therapy but there are fewer available for use in treating fungal and parasitic keratitis. There are also problems with current antimicrobials, such as limited efficacy and the presence of drug-resistant microbes. Thus, there is a need to develop additional drugs. Nature has given us an example of 1 potential source of new antimicrobials: antimicrobial peptides and proteins that are either present in bodily fluids and tissues constitutively or are induced upon infection. Given the nature of peptides, topical applications are the most likely use to be successful and this is ideal for treating keratitis. Such peptides would also be active against drug-resistant pathogens and might act synergistically if used in combination therapy. Hundreds of peptides with antimicrobial properties have been isolated or synthesized but only a handful have been tested against ocular pathogens and even fewer have been tested in animal models. This review summarizes the currently available information on the use of peptides to treat keratitis, outlines some of the problems that have been identified, and discusses future studies that will be needed. Most of the peptides that have been tested have shown activity at concentrations that do not warrant further development, but 1 or 2 have promising activity raising the possibility that peptides can be developed to treat keratitis.
    Journal of Ocular Pharmacology and Therapeutics 09/2014; 30(9).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: Both superficial band keratopathy and deeper calcareous calcification have been linked to the presence of phosphate excipients in topical ophthalmic medicines. (1-3) The European Medicines Agency (EMA) has concluded that patients with ocular surface disease are at greatest risk. This potential side effect should be highlighted to both prescribers and patients. (4) We aimed to review the excipients of commonly prescribed ophthalmic medicines to prepare a list of phosphate-containing drugs and also to investigate where to find this information. Methods: We reviewed 78 commonly used ophthalmic drops and ointments for the information about their excipients. We reviewed the information written on drug boxes, bottles, patient leaflets, and in the electronic Medicines Compendium (EMC), which contains up-to-date details of all medicines licensed for use in the United Kingdom. The British National Formulary (BNF) was also reviewed. Results: We found 22 phosphate-containing, 13 unbuffered, and 43 ophthalmic drugs containing buffers other than phosphate based. Most displayed the list of their excipients on their boxes and in patient leaflets. This information was also available on the EMC website but not in the BNF. Despite the EMA recommendation, none of the phosphate-containing medicines mentions corneal calcification as a potential side effect. Conclusions: We present a reference list of phosphate-based ophthalmic drugs to be used with caution for patients with a compromised ocular surface. We found the EMC to be a reliable and easily accessible source of information about drug components. This information will also be included in the new editions of the BNF.
    Journal of Ocular Pharmacology and Therapeutics 09/2014; 30(10).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To evaluate corneal and conjunctival sensitivity changes following intravitreal ranibizumab (IVR) injection in eyes with diabetic retinopathy. Methods: Forty-six eyes of 46 patients with diabetic macular edema who underwent intravitreal injection of ranibizumab were included in this prospective study. Fifty eyes of 50 type 2 diabetes mellitus patients served as controls. Each participant underwent a complete ophthalmological examination. Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. IVR (0.5 mg/0.05 mL) was injected from the lower temporal quadrant. Corneal and conjunctival sensitivities were measured using the Cochet-Bonnet esthesiometer. Results: Corneal sensitivity (CS) increased significantly at first day in temporal and nasal corneas in treated eyes (P=0.005 and P=0.000, respectively). At first week the increase continued and the difference was significant in central, temporal, and nasal corneas (all P=0.000). In fellow eyes, CS increased significantly only in nasal cornea (P=0.004). Only nasal conjunctival sensitivity increased significantly both in treated and fellow eyes at first week (P=0.000 and P=0.005, respectively). Conclusion: IVR may have a potential to increase corneal and conjunctival sensitivities in diabetic retinopathy.
    Journal of Ocular Pharmacology and Therapeutics 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To evaluate the efficacy and safety of gatifloxacin 0.5% ophthalmic solution administered twice daily for treatment of acute bacterial conjunctivitis. Methods: Two identically designed, double-masked, multicenter studies in the United States and India enrolled patients 1 year or older with acute bacterial conjunctivitis. Patients were randomized to gatifloxacin 0.5% or vehicle treatment for 5 days. Clinical success in clearing conjunctival hyperemia and discharge at day 6 (primary endpoint) and day 4 and microbiological cure were determined. Isolates from positive conjunctival samples were tested for sensitivity and susceptibility. Safety measures included adverse events (AEs). Data from these 2 studies were pooled for these analyses. Results: Of the 1437 randomized patients, 658 constituted the modified intent-to-treat population. Patient characteristics were similar between the pooled treatment groups. Clinical success occurred for 58.0% of gatifloxacin 0.5%-treated versus 45.5% vehicle-treated patients at day 6 (P=0.001) and for 23.7% versus 15.4% in the respective groups at day 4 (P=0.007). Microbiological cure was higher with gatifloxacin 0.5% than vehicle at days 4 and 6 (P<0.001 for both time points). The combined minimum inhibitory concentration required to inhibit 90% of isolates for gatifloxacin 0.5% was 2.0 μg/mL for gram-positive and gram-negative organisms. AEs were reported by 11.6% and 13.3% of patients in the gatifloxacin 0.5% and vehicle safety populations, respectively. One patient in each treatment group experienced a serious AE; neither was treatment related. Conclusions: The 0.5% concentration of gatifloxacin ophthalmic solution was safe and effective for treatment of acute bacterial conjunctivitis with twice-daily administration for 5 days.
    Journal of Ocular Pharmacology and Therapeutics 09/2014; 30(10).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To compare the effects of topical nonsteroidal anti-inflammatory drugs on pupil dilation maintenance during phacoemulsification cataract surgery and quantify the relationships between pupil size change and nuclear hardness. Methods: This prospective randomized clinical observation study was single centered and double-masked. We studied 239 cases undergoing uneventful phacoemulsification cataract surgery in the absence of significant ocular comorbidity. Cases were randomly assigned to 1 of 6 groups receiving the following treatments: (1) diclofenac (0.1%); (2) pranoprofen (0.1%); (3) control, physiological normal saline solution; (4) diclofenac (0.1%) and epinephrine; (5) pranoprofen (0.1%) and epinephrine; (6) control, physiological normal saline and epinephrine solutions. Pupil diameter was measured at 3 intervals of cataract surgery: before the first incision, at the end of nucleus fragmentation, and at the end of cortex irrigation/aspiration. Results: Compared with patients who were not treated, there was a significant difference in maintaining pupil dilation throughout the operation when the patients were treated with either diclofenac or pranoprofen, P<0.001 and P<0.03, respectively. From the first incision to postnucleus fragmentation, the change in pupil size in both diclofenac and control groups was significantly associated with the hardness of the crystalline lens, P=0.001 and P=0.012, respectively. At the end of irrigation/aspiration, the change in pupil size in only the control groups was significantly associated with the hardness of the crystalline lens, P=0.022. Diclofenac treatment was most effective at inhibiting pupil miosis when the hardness of the nucleus was grade 3, P=0.009. Pupil miosis was not related to the hardness of the nucleus when the patients were treated with epinephrine. Conclusions: Both diclofenac and pranoprofen treatment inhibit surgical-induced miosis. There is a negative correlation between the hardness of the crystalline lens and pupil diameter maintenance at the early stage of phacoemulsification.
    Journal of Ocular Pharmacology and Therapeutics 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: There are concerns about arterial thromboembolic event after intravitreal injection of bevacizumab or ranibizumab. Motivated by the fact that D-dimer was a sensitive biomarker for thromboembolism, we evaluated serum D-dimer levels in patients with age-related macular degeneration (AMD) after intravitreal injection of bevacizumab and ranibizumab. Methods: In this prospective, nonrandomized, uncontrolled study, 122 patients (122 eyes) with AMD were enrolled. Sixty-two eyes received intravitreal injections of bevacizumab and 60 eyes received intravitreal injections of ranibizumab monthly for 3 months. Serum D-dimer levels were measured in patients before intravitreal injection and 1 day, 1 week, 1 month, and 3 months thereafter. Results: Serum D-dimer levels were not significantly altered following injection of either bevacizumab or ranibizumab. Subgroup analysis for patients at risk for thromboembolic events revealed that serum D-dimer levels showed no significant change after injection of ranibizumab. However, D-dimer levels significantly increased at 1 day (P=0.041) and 1 week (P=0.022) after injection of bevacizumab. Conclusions: Serum D-dimer levels were not changed after injection with either bevacizumab or ranibizumab. In subgroup analysis, bevacizumab injection in patients at risk of thromboembolism increased serum D-dimer levels.
    Journal of Ocular Pharmacology and Therapeutics 09/2014;