Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study.

PURPOSE: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Participants with ≥5 VFs (213 placebo, 217 treatment). METHODS: Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms. MAIN OUTCOME MEASURES: Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations. RESULTS: In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 µm thicker; P = 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression. CONCLUSIONS: No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparative Study of Latanoprost Drug Delivery Systems for Glaucoma Treatment and Their Interaction with the Tear Film Lipid Layer Models.

This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.

A triple combination of latanoprost, fractional CO2 laser, and platelet-rich plasma in localized vitiligo: A clinical and histopathologic study.

BACKGROUND: Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies. OBJECTIVES: We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO2 laser or fractional CO2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo. PATIENTS/METHODS: The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation. RESULTS: Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO2 or latanoprost alone. CONCLUSION: Fractional CO2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

Timolol maleate, a ß blocker eye drop, improved edema in a retinal vein occlusion model.

Purpose: To investigate the therapeutic effects of eye drops, namely, timolol maleate, a ß-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model. Methods: An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema. Results: Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO. Conclusions: These results indicate that timolol eye drops may be a potential option for RVO treatment.

Primary Open-Angle Glaucoma Progression in Glaucoma Patients with Unchanged Topical Treatment over 3 Years - Retrospective Observational Cohort Analysis.

BACKGROUND: Lowering intraocular pressure (IOP) is a mainstay of glaucoma therapy. It is, however, still an open question whether a comparable level of long-term IOP lowering achieved by different medications results in comparable protection for the retinal ganglion cells. The purpose of this study was to retrospectively analyze glaucoma damage progression in two cohorts of primary open-angle glaucoma patients with different and unchanged therapy over a period of 3 years, and the main objective of this study was to determine possible differences in terms of structural [retinal nerve fiber layer thickness (RNFL)] and functional [visual field (VF)] outcome. PATIENTS AND METHODS: The retrospective observational cohort analysis compared two differently treated groups of glaucoma patients with their original, at study entry, topical therapy unchanged over 3 years. The main endpoint was the time course of RNFL thickness and VF mean defect (MD). RESULTS: Twenty-one eyes were included in each group. The first group (21 eyes) was on a fixed combination of timolol and dorzolamide twice a day and the second group on one drop of prostaglandin analog, either latanoprost alone (15 eyes) or travoprost alone (6 eyes), in an unchanged regimen over a period of 3 years. IOP in mmHg at baseline and at 36 months was 11.9 ± 2.4 and 13.0 ± 2.1 in the first, and 12.9 ± 3.0 and 14.1 ± 3.2 in the second group, respectively. RNFL thickness values in micrometers were at baseline and at 36 months 77.8 ± 12.3 and 76.6 ± 15.2 in the first, and 77.5 ± 15.2 and 72.8 ± 14.5 in the second group, respectively. VF MD in dB were 1.7 ± 2.5 and 1.2 ± 2.9 in the first, and 0.9 ± 2.3 and 0.7 ± 2.6 in the second group, respectively. CONCLUSION: Both groups had comparable baseline, as well as mean overall IOP. However, the course of IOP levels over time was different in the two groups, showing earlier and more pronounced long-term drift in the prostaglandin analog-treated group. RNFL thickness was comparable at baseline, however, RNFL thinning over time was more pronounced in the prostaglandin analog-treated group. There were no statistical differences between the groups in terms of VF MD at baseline and over time.

A Non-Inferiority Study of Combination of Latanoprost and Timolol Formulation to Their Separate Use in Drug-Naive Primary Open Angle Glaucoma and Ocular Hypertension Nigerian Patients. {RCT 93803536 (Nigeria Clinical Trial Registry)}.

BACKGROUND: Control of intraocular pressure continues to be the mainstay of the management of primary open-angle glaucoma. It is also one of the key factors to consider in the diagnosis and risk of conversion of ocular hypertension to glaucoma (POAG). Medical management of IOP control is central to the treatment of POAG especially in resource-poor countries. AIM: This study aimed to demonstrate the non-inferiority of a fixed combination of front-line drugs in the medical management of glaucoma (latanoprost and timolol) compared to concomitant use of the same drugs. METHODOLOGY: It was a double-blind, randomized clinical trial (RCT) in which 116 sequentially consenting participants 40 years and above were recruited and randomized to receive either a fixed combination (group A) or a concomitant combination of latanoprost and timolol (group B). The study was carried out across two tertiary centers in southwest Nigeria. RESULTS: One hundred and fifteen (115) patients were analysed, 58 in group A and 57 in group B. The mean age of participants was 57.9 (± 11.5) years. There were 51 (44.3%) females. Primary open-angle glaucoma (POAG) was the diagnosis in 88 (76.5%) of the participants. No statistically significant difference between the two groups at recruitment. Mean IOP reduction from baseline to day 28 was -17.30 ± 7.8 (95% CI: -15.37 to -19.15), and -14.59 ± 6.1 (95% CI: -12.98 to -16.19) for groups A and B. Group A thus had a 54.97% IOP reduction from baseline values while group B had 51.81% (p = 0.770). The mean intergroup difference (MeD) in IOP reduction (µA - µB) between the two groups on day 28 was 2.05 ± 5.74 (95% CI: 0.6 - 1.61) p=0.04. CONCLUSION: The study was able to demonstrate a noninferiority relationship between the fixed combination dosage form of latanoprost and timolol as compared to the concomitant dosage forms.

CONTEXTE: Le contrôle de la pression intraoculaire reste le pilier de la prise en charge du glaucome à angle ouvert primaire. C'est également l'un des principaux facteurs à considérer dans le diagnostic et le risque de conversion de l'hypertension oculaire en glaucome (POAG). La gestion médicale du contrôle de la pression intraoculaire est essentielle dans le traitement du POAG, surtout dans les pays à ressources limitées. OBJECTIF: Cette étude visait à démontrer la non-infériorité d'une combinaison fixe de médicaments de première ligne dans la gestion médicale du glaucome (latanoprost et timolol) par rapport à l'utilisation concomitante des mêmes médicaments. MÉTHODOLOGIE: Il s'agissait d'un essai clinique randomisé en double aveugle dans lequel 116 participants consécutifs âgés de 40 ans et plus ont été recrutés et répartis de manière aléatoire pour recevoir soit une combinaison fixe (groupe A) soit une combinaison concomitante de latanoprost et de timolol (groupe B). L'étude a été menée dans deux centres tertiaires du sud-ouest du Nigeria. RÉSULTATS: Cent quinze (115) patients ont été analysés, 58 dans le groupe A et 57 dans le groupe B. L'âge moyen des participants était de 57,9 (± 11,5) ans. Il y avait 51 (44,3%) femmes. Le glaucome à angle ouvert primaire (POAG) a été diagnostiqué chez 88 (76,5%) des participants. Aucune différence statistiquement significative entre les deux groupes au moment du recrutement. La réduction moyenne de la pression intraoculaire entre le début et le jour 28 était de -17,30 ± 7,8 (IC à 95% : -15,37 à ­19,15) et de -14,59 ± 6,1 (IC à 95% : -12,98 à -16,19) pour les groupes A et B. Le groupe A a ainsi présenté une réduction de 54,97 % de la PIO par rapport aux valeurs initiales tandis que le groupe B a enregistré 51,81 % (p = 0,770). La différence moyenne intergroupes (DMI) dans la réduction de la PIO (µA ­ µB) entre les deux groupes au jour 28 était de 2,05 ± 5,74 (IC à 95% : 0,6 ­ 1,61) p = 0,04. CONCLUSION: L'étude a pu démontrer une relation de noninfériorité entre la forme posologique fixe de latanoprost et de timolol par rapport aux formes posologiques concomitantes. MOTS-CLÉS: Glaucoma, Hypertension oculaire, Contrôle de la PIO, Nigérians, Latanoprost, Timolol, Hypotenseurs oculaires, Combinaison fixe, Patients naïfs aux médicaments.

Effects of topical prostaglandin therapy on corneal layers thickness in primary open-angle glaucoma patients using anterior segment optical coherence tomography.

PURPOSE: To evaluate the effects of latanoprost, bimatoprost, and travoprost eye drops and their preservatives on each corneal layer thickness in patients with primary open-angle glaucoma (POAG). METHODS: We retrospectively analyzed 79 eyes of 79 patients with POAG who were receiving prostaglandin therapy. Patients were divided into three subgroups according to monotherapy with latanoprost, bimatoprost, and travoprost during a mean of 43.14 ± 19.12 months follow-up period. In addition, the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) were measured by anterior segment optical coherence tomography (AS-OCT) at baseline and every six months after treatment initiation at each visit between 9 and 12 o'clock in the morning. Furthermore, intraocular pressure (IOP) was measured with Goldmann applanation tonometry (GAT) after AS-OCT measurements at each visit. RESULTS: All three groups were not significantly different in age, gender, follow-up period, and mean intraocular pressure values (p > 0.05 for all). The reduction of CCT in the latanoprost, bimatoprost, and travoprost groups was 6.53 ± 3.17, 18.59 ± 8.42, and 10.1 ± 1.13 µm, respectively. The decrease in CST values was 4.65 ± 1.54, 15.84 ± 7.47, 9.69 ± 1.45 µm, and CET values were 1.88 ± 1.66, 2.75 ± 0.73, 0.41 ± 0.54 µm in all groups, respectively. A statistically significant thinning was observed in all corneal layers (p < 0.05) except the CST values in the latanoprost group and CET values in the travoprost group. However, no significant difference was found in the average reduction of CET, CST, and CCT values among the three groups (p > 0.05). CONCLUSION: Topical treatment with latanoprost, bimatoprost, and travoprost affects each layer of the cornea separately according to the active and protective substances contained in these eye drops. On the other hand, the thinning effect on the corneal layers was similar in these three drugs because there was no significant difference between the three groups in the total amount of thinning of the corneal layers during the follow-up period.

Noninferiority Study Comparing Latanoprost 0.005% Without Versus With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension.

OBJECTIVES: To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension). METHODS: Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE). RESULTS: The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups. CONCLUSIONS: Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

Comparative effects of latanoprost and latanoprostene bunod on intraocular pressure and pupil size in ophthalmologically normal Beagle dogs.

OBJECTIVE: To compare effects of latanoprost, a topical prostaglandin analogue (PGA) commonly used to treat glaucoma and lens instability in dogs, and latanoprostene bunod, a novel PGA with a nitric oxide-donating moiety, on intraocular pressure (IOP) and pupil diameter (PD). ANIMALS STUDIED: Ten ophthalmologically normal Beagle dogs. PROCEDURES: Dogs were treated twice a day for 5 days in a randomly selected eye with either latanoprost or latanoprostene bunod. After a 6-week washout period, dogs were treated with the opposite drug. IOP and PD were measured at treatment times, at midday on days 1 and 5, and for 6 days post-treatment. RESULTS: Both drugs significantly decreased IOP and PD. At midday on day 5 of treatment, mean IOP in eyes treated with latanoprost was 4.5 mmHg lower than the fellow eye and 3.0 mmHg lower than the same eye at baseline, while mean IOP in eyes treated with latanoprostene bunod was 5.5 mmHg lower than the fellow eye and 3.6 mmHg lower than baseline. Mean PD was 0.94 mm in eyes treated with latanoprost and 0.76 mmHg in eyes treated with latanoprostene bunod. There was no significant difference between the two drugs for either parameter at that time point (p = .372 and .619, respectively, for IOP relative to control and to baseline; p = .076 for PD) or when analyzed longitudinally. Significant diurnal variation in PD was noted and may have implications for treatment of lens' instability. CONCLUSIONS: Latanoprost and latanoprostene bunod produce similar IOP reduction and miosis in normal canine eyes.

Sustained latanoprost release from PEGylated solid lipid nanoparticle-laden soft contact lens to treat glaucoma.

Contact lens have been proposed as a mean of ocular drug delivery, but the conventional soaking method to load hydrophobic drugs, such as latanoprost shows low drug loading and high burst release with alteration in the critical lens properties. In this paper, a novel latanoprost-loaded PEGylated solid lipid nanoparticles (LP-pSLNs) were developed to increase the latanoprost loading capacity of contact lenses (LP-pSLN-L), while also sustaining ocular drug delivery. The pSLNs were spherical in shape with an average size of 105‒132 nm (nanometer) and a zeta potential ranging from ‒29.1 to ‒26.7 mV (millivolt). The LP-pSLNs led to improved swelling, transmittance, and protein adherence of the lens compared to the non-pegylated SLNs congeners (LP-SLN-L) and conventional soaked lens (LP-SM-L). The LP-SM-L lens showed low drug loading, high burst release, and a short release duration of 24 h. The LP-SLN-L and LP-pSLN-L lenses showed high drug uptake and sustained drug release up to 120 h and 96 h, respectively. The pegylation reduced the size of nanoparticles and improved the drug loading capacity, while the release rate was high in the initial hours. The LP-pSLN-L lens was found to be safe based in histopathological studies. In animal studies, the LP-pSLN-10-L batch showed high drug concentration at all-time points up to 96 h compared to the LP-SM-L and eye drop solution. In conclusion, pSLNs improved the latanoprost loading in the contact lens and showed sustained drug release, and thus can be used as a substitute to eye drop therapy.

[Neuroprotective properties of latanoprost]. / Neiroprotektornye svoistva latanoprosta.

Glaucoma is the main cause of irreversible blindness in the world. Latanoprost - an ester prodrug of prostaglandin F2α (PGF2α) - was the first prostaglandin analogue used to treat glaucoma. The review shows that latanoprost possesses direct neuroprotective properties such as blocking the entry of calcium ions into neurons and inhibiting the action of caspase-3, inhibiting the activity of cyclooxygenase and activation of polypeptide 2B1 (OATP2B1) and Klotho protein. It is emphasized that when the drug is instilled into the eye, the concentration of the drug inside the vitreous body is twice as high as what is required to ensure the survival of retinal ganglion cells.

[Xalacom: possibilities and advantages of the drug in the treatment of patients with glaucoma]. / Ksalakom: vozmozhnosti i preimushchestva preparata v terapii glaukomy.

The strategy of glaucoma therapy is aimed at preserving visual functions and ensuring an acceptable quality of life for patients. To achieve this strategic goal, clinicians in their practice use drugs that affect the main factor in the progression of the disease - intraocular pressure (IOP), aiming to reduce it to an individual target level. It is not always possible to achieve optimal IOP values with monotherapy. Many patients require a combination of drugs from different pharmacological groups. Xalacom is a fixed drug with good tolerability and t hypotensive effect. This review focuses on the benefits of this drug for the treatment of glaucoma.

Corneal epithelium and limbal region alterations due to glaucoma medications evaluated by anterior segment optic coherence tomography: a case-control study.

AIM: To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency. METHODS: Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed. RESULTS: A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (p < 0.001). The mean central corneal epithelium thickness was 48.5 ± 5.3 in patients and 54.5 ± 5.9 in controls (p < 0.001). The mean central total corneal thickness was 529.2 ± 41.2 in patients and 536 ± 35.3 in controls (p = 0.335). The mean limbal epithelium thickness was 64.1 ± 9.1 in patients and 76 ± 11.5 in controls (p < 0.001). CONCLUSION: Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

Risk Factors for Visual Field Deterioration in the United Kingdom Glaucoma Treatment Study.

PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) investigated the visual field (VF)-preserving effect of medical treatment in open-angle glaucoma (OAG). The objective of this analysis was to identify risk factors associated with VF deterioration. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Five hundred sixteen participants with previously untreated OAG were recruited prospectively in 10 United Kingdom centers. METHODS: Eligibility criteria were modeled on those for the Early Manifest Glaucoma Trial. Study participants were randomized to either latanoprost 0.005% or placebo eye drops. The observation period was 2 years and involved, among other procedures, VF testing and intraocular pressure (IOP) measurement at 11 scheduled visits, with clustering of tests at baseline, 18 months, and 24 months. Guided progression analysis pattern deviation maps were used to determine VF deterioration. Cox regression was used to compute the hazard ratios (HRs) and respective 95% confidence intervals (CIs) while accounting for the correlation within sites. Model selection was guided by backward stepwise selection conducted on the model containing all variables that were significant at the 0.2 level in the univariate analysis. Follow-up variables that showed collinearity with baseline values were not retained in the final model. MAIN OUTCOME MEASURE: Time to VF deterioration. RESULTS: Treatment with latanoprost reduced the HR, for VF deterioration by 58% (HR, 0.42; 95% CI, 0.27-0.67; P = 0.001). Factors associated with deterioration were bilateral disease (HR, 1.59 for yes vs. no; 95% CI, 1.02-2.50; P = 0.041), higher baseline IOP (HR, 1.07 per mmHg; 95% CI, 1.02-1.12; P = 0.008), and disc hemorrhage at visit 1 (HR, 2.08; 95% CI, 1.07-4.04; P = 0.030). Smoking (current or previous) was associated with a reduced HR, for VF deterioration (HR, 0.59; 95% CI, 0.37-0.93; P = 0.023). No other evaluated factors were found to be statistically significant in the multivariable analysis. CONCLUSIONS: In the UKGTS, treatment with latanoprost halved VF deterioration risk. Bilateral disease, higher IOP, and disc hemorrhage were confirmed as risk factors for deterioration; smoking history seemed to be protective against VF deterioration.

Effectiveness of Blepharoptosis Surgery in Patients With Deepening of the Upper Eyelid Sulcus.

The purpose of this retrospective study was to evaluate the effectiveness of blepharoptosis surgery in patients with deepening of the upper eyelid sulcus (DUES). This case series included 10 consecutive patients (19 eyes) with DUES associated with use of a prostaglandin analog for glaucoma. Patients who had used bimatoprost and developed DUES were changed to an alternative prostaglandin analog and observed for ≥3 months. If there was no improvement, they underwent levator resection for blepharoptosis and were followed up for ≥6 months postoperatively. Improvement in margin reflex distance-1 and surgical complications was evaluated. After discontinuation of bimatoprost in 3 cases (6 eyes), mild subjective and objective improvement in DUES was seen in 2 cases (4 eyes) but without improvement in blepharoptosis. The prostaglandin analog used before surgery was travoprost in 4 eyes (21.0%), tafluprost in 7 eyes (36.9%; including 4 eyes switched from bimatoprost), and latanoprost in 8 eyes (42.1%; including 2 eyes switched from bimatoprost). The mean margin reflex distance-1 value was 1.11 ±â€Š0.96 mm before surgery and 3.72 ±â€Š0.81 mm at the final postoperative follow-up; the difference was significant (P = 3.32 × -10). There were no intraoperative or postoperative complications. Levator resection is a useful and safe procedure for blepharoptosis with DUES.

Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia.

Latanoprost has recently been used to treat alopecia as it causes an increase in the capillary density of patients. This work presents for the first time the development of polymeric nanocapsules containing latanoprost for the topical treatment of alopecia. Poly-ε-caprolactone nanocapsules loading latanoprost were developed by nanoprecipitation of the polymer on the surface of drug oily nanodroplets. The method encapsulated 93.9 ± 0.4% of the drug into nanocapsules of 197.8 (± 1.2) nm (PdI = 0.15 ± 0.01). The nanosystem presented a zeta potential equal to - 30.1 ± 1.8 mV and was stable for at least 90 days when stored at 6°C. The colloidal aqueous dispersion was non-irritating, according to the in vitro HET-CAM test. The nanocapsules improved latanoprost accumulation into the hair follicles when topically applied on porcine skin, delivering 30% more drug to these skin structures relative to the control solution (P < 0.05). Also, with a simple manual massage, latanoprost accumulation was increased by twofold (P < 0.05). In conclusion, in addition to being a stable and safe formulation, nanocapsules enhanced latanoprost accumulation into the hair follicles, being a nanosystem with high potential for use as a topical formulation for the treatment of androgenic alopecia.

Treatment of canine postoperative ocular hypertension with combined latanoprost 0.005% and atropine 1% ophthalmic solutions.

OBJECTIVE: To compare the effects of topical 0.005% latanoprost (L) vs combined 0.005% latanoprost and 1% atropine (LA) on control of postoperative ocular hypertension (POH), development of posterior synechiae formation, pupil size, and blindness after phacoemulsification surgery in dogs. ANIMAL STUDIED: Dogs with postoperative ocular hypertension were included in the study: L-group, latanoprost (eight dogs, 14 eyes) and LA-group, latanoprost and atropine (nine dogs, 15 eyes). PROCEDURES: Complete ophthalmic examinations including tonometry were performed at 1, 7, and 21 days following phacoemulsification. RESULTS: No significant differences were found between the measured intraocular pressure (IOP) at days 1 and 7 postphacoemulsification surgery in the L-group and the LA-group (P = 0.26 [14.12 ± 1.76 mmHg vs 16.96 ± 1.68 mmHg] and P = 0.71 [15.45 ± 1.43 mmHg vs 16.20 ± 1.36 mmHg], respectively). No significant differences were found between pupil sizes at day 7 for the two groups (P = 0.25 [13.83% vs 24.77%]). No significant differences were found between odds of posterior synechiae formation at day 21 (P = 0.92) with a probability ± SE for L-group vs LA-group at 0.27 ± 0.14 vs 0.25 ± 0.13. No significant differences were found in odds of postoperative blindness between groups (P = 0.58) with a probability ± SE of 0.21 ± 0.11 vs 0.13 ± 0.09, respectively for L and LA. CONCLUSIONS: Combined topical latanoprost and atropine in dogs maintains normal postoperative IOPs but does not seem to cause increased mydriasis compared to latanoprost alone.

Effect of Topical Prostaglandin F2α Analogs on Selected Oxidative Stress Parameters in the Tear Film.

Background and Objectives: Topically administered antiglaucoma medications, especially those containing benzalkonium chloride (BAC), may cause local adverse effects and compromise ocular surface. The aim of the study was to assess the effect of topical prostaglandin F2α analogs (PGAs): preservative-free latanoprost, BAC-preserved latanoprost, preservative-free tafluprost, and BAC-preserved bimatoprost, on selected oxidative stress parameters in the tear film. Materials and Methods: The patients were divided into five groups: group C (n = 25) control group-subjects who did not use topical antiglaucoma medications, group L (n = 22)-patients using topical preservative-free latanoprost, group L+BAC (n = 25)-patients using topical BAC-preserved latanoprost, group T (n = 19)-patients using topical preservative-free tafluprost, and group B+BAC (n = 17)-patients using topical BAC-preserved bimatoprost. The oxidative stress markers in the tear film samples were evaluated: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). Results: The TP concentrations in the groups L, L+BAC, and B+BAC were statistically significantly higher in comparison with group C. The SOD and CAT activities in the groups L+BAC and B+BAC were statistically significantly higher when compared to group C. As compared to group C, AOPP and TOS were statistically significantly higher in all the study groups. OSI was found to be statistically significantly higher in the groups L+BAC, T, and B+BAC in comparison with group C. Conclusion: Use of topical PGAs by the patients with ocular hypertension or primary open-angle glaucoma is associated with increased oxidative stress in the tear film which is additionally exacerbated by the presence of BAC in the formulation.

The Effects of Latanoprost With Benzalkonium Chloride Versus Travoprost With SofZia on the Ocular Surface.

PURPOSE: To assess ocular surface changes in participants using latanoprost with benzalkonium chloride (Xalatan) and travoprost with SofZia (Travatan Z). METHODS: In this prospective, open-label, nonrandomized cohort study, participants were classified into two groups: group 1 (n=28) naive to glaucoma therapy, group 2 (n=27) on previous Xalatan monotherapy in both eyes. Both groups started (or continued) Xalatan in the right eye and Travatan Z in the left eye. Baseline, 1-, and 2-month measurements of tear breakup time (TBUT), corneal staining score, conjunctival staining score, conjunctival hyperemia score, tear production, and intraocular pressure were obtained. The Ocular Surface Disease Index questionnaire measured participants' comfort and dryness symptoms. Medication preference was recorded. RESULTS: Data were collected from 55 participants. Tear breakup time at baseline and 1-month follow-up in group 1 was significantly longer than that of group 2 (P=0.005). At 2 months, there was no significant difference in TBUT between the two groups (P=0.779). Tear production in group 1 at all three time points was significantly higher than group 2 (P<0.05). Conjunctival staining score at 2 months in group 1 was significantly higher than group 2 (P=0.031). There was no significant difference in other parameters between the groups at any other time point. No significant difference in any parameter was found between Xalatan and Travatan Z (intragroup comparison). CONCLUSIONS: Significant differences in ocular surface characteristics were detected between groups, but no significant difference was detected between participants treated with Xalatan and Travatan Z.