Topical Prostaglandin Analogues Research Articles

Preservative-free fixed combination in the treatment of open-angle glaucoma and ocular hypertension: the VISIONARY Study (EUPAS22204)

To evaluate efficacy, tolerability, and safety of PF tafluprost/timolol FC in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OH) who couldn't tolerate or gave insufficient response to topical beta-adrenoblockers or prostaglandin analogue monotherapy. The prospective multicenter European VISIONARY study (EUPAS22204) included 87 patients from 7 ophthalmological centers in Russia with mean age of 63.9±11.8. Primary endpoint was mean IOP change at month 6. The patients were monitored for changes in in the severity of ocular signs and symptoms. Statistically significant (p<0.0001) reduction of mean IOP from baseline was seen at all study visits: 7.3±5.17 mmHg at week 4, 7.4±5.40 mmHg at week 12, and 7.1±5.10 mmHg at month 6. By month 6, IOP has decreased by 20; 25; 30 and 35% from baseline in 77.0%, 58.9%, 43.7%, and 31.0% of study patients, respectively. Conjunctival hyperemia was significantly reduced at all study visits. Significant reductions in dry eye symptoms (p<0.0010), irritation (p=0.0204) and itching (p=0.0010) were also observed. After 6 months on PF tafluprost/timolol FC, 85.7% of patients described it as easy or very easy to tolerate. In clinical practice, PF tafluprost/timolol FC provided statistically significant IOP reductions in patients with POAG and OH insufficiently controlled by or intolerant to monotherapy with topical beta-adrenoblockers or a prostaglandin analogue. The highest IOP reduction was seen at week 4 and was maintained over the 6-month study period. There was also a decrease in the severity of symptoms of ocular surface condition.

A preclinical study of the intraocular pressure lowering efficacy of bimatoprost sustained release in eyes pretreated with selective laser trabeculoplasty

AbstractPurposeSelective Laser Trabeculoplasty (SLT) is a treatment for lowering intraocular pressure (IOP) in patients with glaucoma, however IOP‐lowering is not sustained after SLT over long term in a substantial proportion of patients. Recent human studies found less reduction in IOP when SLT and topical prostaglandin analogues (PGA) were used in combination. Bimatoprost Sustained Release (BimSR) implant is currently in development as an IOP‐lowering agent delivered intracamerally (IC). The purpose of this study was to assess the efficacy of BimSR in both eyes of a cohort of dogs following unilateral SLT treatment.MethodsUnilateral SLT was performed in 11 female, normotensive, drug‐naïve beagle dogs. IOP was monitored up to 10 weeks following SLT. Six to ten weeks post SLT, nine of 11 eyes returned to their baseline IOP. Dogs were administered BimSR (15 μg) IC in both eyes. Percent change in IOP from baseline was calculated in SLT‐treated and naïve eyes. Data expressed as mean ± SE. A linear mixed effects model was used to evaluate the treatment effect of BimSR in SLT‐treated and contralateral SLT‐naïve eyes.ResultsBimSR was equally efficacious in lowering IOP in both SLT‐treated and SLT‐naïve eyes. Mean percent decrease in IOP following BimSR administration to SLT‐treated eyes was 34.2% ± 2.8 and 34.7% ± 1.7 in contralateral, SLT‐naïve eyes. BimSR lowered IOP equally in eyes that responded to SLT (sustained decrease in IOP of ≥3 mmHg in the laser treated eye, n = 6, mean percent IOP decrease, 34.3% ± 4.2) and eyes that did not respond to SLT treatment (decrease in IOP of &lt;3 mmHg in the laser treated eye, n = 5, mean percent IOP decrease, 34.1% ± 2.7).ConclusionsIntracameral BimSR had substantial IOP‐lowering effects in eyes previously treated with SLT, suggesting that eyes that have been treated with SLT can still benefit from IC drug delivery of the BimSR implant. Importantly, BimSR was effective in lowering IOP in eyes that were previously non‐responders to SLT.

Topical Prostaglandin Analog Use Is Associated with Increased Failure Rate of Ptosis Repair

Topical Prostaglandin Analog Use Is Associated with Increased Failure Rate of Ptosis Repair

Monotherapy for Alopecia Areata: A Systematic Review and Network Meta-Analysis

Background: There are many treatments available for alopecia areata; however, none are approved by the US Food and Drug Administration. Thus, there is clinician benefit in efficacy comparison. Methods: A network meta-analysis was used to create direct and indirect comparisons of alopecia areata studies in addition to an inconsistency analysis, risk of bias, and quality of evidence assessment. Results: For mild disease, intralesional corticosteroids were ranked the most likely to produce a response at 78.9% according to SUCRA (surface under the cumulative ranking curve) followed by topical corticosteroids (67.9%), prostaglandin analogs (67.1%), diphenylcyclopropenone (DPCP, 63.4%), topical minoxidil (61.2%), and squaric acid dibutylester (SADBE, 35.0%). In contrast, for moderate to severe disease (>50% scalp hair loss), DPCP was the top-ranked treatment (87.9%), followed by laser (77.9%), topical minoxidil (55.5%), topical corticosteroids (50.1%), SADBE (49.7%), and topical tofacitinib (47.6%). There were insufficient eligible trials to include oral tofacitinib in the network. Conclusion: Statistically significant evidence is presented for the use of intralesional and topical corticosteroids for treatment of mild disease and DPCP, laser, SADBE, topical minoxidil and topical corticosteroids for moderate to severe disease. Further controlled trials are required to analyze the relative efficacy of oral tofacitinib.

Episcleral Venous Pressure and the Ocular Hypotensive Effects of Topical and Intracameral Prostaglandin Analogs.

There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular hypotensive efficacy with topical dosing. Intracameral PGA dosing with a bimatoprost implant, however, does not exhibit the same intraocular pressure (IOP)-lowering plateau at studied concentrations, and the maximum-achievable ocular hypotensive effects are not yet known. This suggests that the bimatoprost intracameral implant may activate another mechanism of action in addition to the mechanism(s) activated by topical application. Episcleral venous pressure (EVP) is a key determinant of IOP, and experimental manipulation of the episcleral vasculature can change both EVP and IOP. The recent observation that topical and intracameral PGA drug delivery routes produce different patterns of conjunctival hyperemia suggested that the differences in the IOP-lowering profiles may be caused by differing effects on the episcleral vasculature. Recent experiments in animals have shown that topical PGAs increase EVP, while the bimatoprost intracameral implant causes a smaller, transient increase in EVP, followed by a sustained decrease. The increase in EVP could be limiting the IOP-lowering efficacy of topical PGAs. In contrast, the decrease in EVP associated with the bimatoprost implant could explain its enhanced IOP-lowering effects. Further research on EVP as a target for IOP lowering is indicated to improve our understanding of this potentially important pathway for treating patients with glaucoma.

Effects of aqueous suppressants and prostaglandin analogues on early wound healing after glaucoma implant surgery

A hypertensive phase frequently develops in the early postoperative period after glaucoma shunt operations. Anti-glaucoma eye drop use is essential when postoperative intraocular pressure (IOP) is not controlled. We investigated whether the use of early topical anti-glaucoma medication affects wound healing following glaucoma tube surgery. Eyes were randomly assigned to receive topical aqueous suppressant (timolol-dorzolamide fixed combination), prostaglandin (PG) analogue (travoprost), or normal saline (control group). First, we observed the effects of topical eye drops on Tenon’s tissue in non-operated eyes in rabbits. Second, we examined the effects of these eye drops on rabbit eyes that underwent Ahmed glaucoma drainage device implantation, including the effects on the histopathological appearance of their blebs. Interleukin-2 in the Tenon’s tissue was elevated in the PG group when compared to the control and aqueous suppressant groups (P = 0.006). In non-operated eyes, IOP was similar among the groups (P = 0.545). After glaucoma implant surgery, the average height of the inner collagenous layer and the average height of the α-SMA-positive blebs were the least in the aqueous suppressant group (P = 0.013, P = 0.001, respectively) at 4 weeks postoperatively. IOP was lower in the aqueous suppressant group than that in the control and PG groups (P = 0.001) following tube surgery. After Ahmed tube surgery, early treatment with aqueous suppressant decreased fibrosis in the bleb, but early treatment with the PG analogues did not.

Shortening of Interpupillary Distance after Instillation of Topical Prostaglandin Analog Eye Drops

To investigate changes in the interpupillary distance (IPD) after continual instillation of topical prostaglandin analogs (PGAs) in glaucoma patients as an objective indicator of prostaglandin-associated periorbitopathy (PAP). Retrospective, comparative case series. A total of 152 institutional patients with glaucoma were enrolled in this study. Inclusion criteria were visual acuities exceeding 10/20 bilaterally and no intraocular surgery during observation. Intervention/observation procedures: First-time bilateral instillation of bimatoprost, travoprost, latanoprost, or tafluprost and IPDs measured by automatic refractometry. IPDs, intraocular pressures (IOPs), and refractive errors were measured before and after continual drug administration (treatment, 2-24months). Post-treatment changes in IPDs. A total of 61 untreated patients served as controls. The IPDs shortened significantly (P < 0.001) after treatment (-0.80 ± 2.1mm); the IPDs of control subjects remained unchanged (0.05 ± 0.96mm; P= 0.69). The IPD change after bimatoprost instillation (-2.20 ± 0.97mm) was significantly (P < 0.001) greater than with other PGAs (-0.65 ± 2.09mm). The IOPs decreased significantly (P < 0.001) (-3.7 ± 4.3mm Hg); the refractive errors did not change significantly (P < 0.099) (-0.07 ± 0.69 diopter) post-treatment. The percentages of subjects with 2-mm or greater decreases in IPD after bimatoprost, travoprost, latanoprost, or tafluprost were 85.7%, 20.0%, 18.2%, and 17.2%, respectively, and with 3-mm or greater decreases in IPD 35.7%, 12.0%, 14.5%, and 12.1%, respectively. The specificities were 93.4% and 100% in the control group, respectively, with IPD threshold changes of 2 and 3mm or more, respectively. The IPD decreased significantly after topical PGAs within 24months. The effect was significantly greater with bimatoprost than with other PGAs. The noninvasive, immediate automatic refractometry measurement may be an objective numerical indicator of PAP.

Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues.

Purpose: To explore the ocular distribution of bimatoprost after intracameral administration of a biodegradable sustained-release bimatoprost implant (Bimatoprost SR) versus repeated topical administration of bimatoprost 0.03% ophthalmic solution in dogs. Bimatoprost SR and topical bimatoprost 0.03% previously were shown to have similar intraocular pressure-lowering effects in humans in a phase 1/2 clinical trial.Methods: Twenty-four beagle dogs received either once-daily topical bimatoprost 0.03% for 7 days or a bilateral intracameral administration of Bimatoprost SR (15 μg). At predetermined time points, ocular tissues were collected and concentrations of bimatoprost and bimatoprost acid were quantified using liquid chromatography–tandem mass spectrometry.Results: Bimatoprost SR administration enhanced delivery of study drug to a site of action [iris–ciliary body (ICB)] compared with topical bimatoprost (Cmax [bimatoprost+bimatoprost acid] = 18,200 and 4.13 ng/g, respectively). However, distribution of drug to tissues associated with prostaglandin analog (PGA)-related side effects (i.e., bulbar conjunctiva, eyelid margins, and periorbital fat) was limited following Bimatoprost SR administration (Cmax [bimatoprost+bimatoprost acid] = BLQ [beneath the limit of quantitation] to 0.354 ng/g) compared with topical dosing (Cmax [bimatoprost+bimatoprost acid] = 36.6–2,110 ng/g).Conclusions: Bimatoprost SR administration in dogs selectively delivered drug to the ICB with low or undetectable drug levels in ocular surface and extraocular tissues. Use of Bimatoprost SR for glaucoma treatment may reduce the incidence of adverse events typically associated with topical PGAs by targeting bimatoprost delivery to the key site of action of the PGA class and reducing exposure to off-target tissues.

Dynamics of changes in morphometric parameters of the macular zone in glaucoma patients after phacoemulsification

To analyze the dynamics of morphometric changes in the macular zone using optical coherence tomography (OCT) data in patients with primary open-angle glaucoma (POAG) after phacoemulsification (PE). The study enrolled 93 patients (95 eyes) requiring PE; they were divided into 2 groups. The first (control) group consisted of 30 patients (32 eyes) without concomitant eye pathology. The second group included 63 patients (64 eyes) with POAG and IOP stabilized by eye drops. In the 2A subgroup (32 eyes) patients used prostaglandin analogues, in the 2B subgroup (31 eye) - carbonic anhydrase inhibitors. OCT was used to analyze retinal thickness and volume. OCT was performed before PE, after 1 week, after 1, 3, and 6 months. In the control group, the volume and thickness of the retina varied within the normal range. In the 2A subgroup, signs of macular edema (ME) in the early post-operative period were noted in 6.2% of patients. In the late post-operative period, changes in the macular zone were noted in 18.7% of cases. After the treatment, ME regressed completely in 4 patients (12.5% of all cases). One patient with retinal thickness of more than 500 µm required parabulbar and intravenous injections of glucocorticoids, which resulted in ME decrease. Another patient developed epiretinal fibrosis with tractions after ME. Among the patients of subgroup 2B, a trend for increase in the volume and thickness of the macular zone was observed in 3 cases; the values stayed within the normal range, and later returned to the initial level. Patients with POAG develop ME after PE in 1-3 months. The use of topical prostaglandin analogues may be the reason of ME development.

Effectiveness of 0.1% topical salicylic acid on blepharoconjunctivitis affecting glaucoma patients treated with topical prostaglandin analogues: a prospective randomized trial.

To evaluate the efficacy of 0.1% topical salicylic acid (TSA) to treat iatrogenic chronic blepharoconjunctivitis in patients with primary open angle glaucoma (POAG), treated with topical prostaglandin analogues (TPAs). Totally 60 patients were randomly distributed into 3 equal size groups, two of which treated with 0.1% TSA (OMKASA®) and 0.1% topical clobetasone butyrate (TCB; VISUCLOBEN®) respectively, and one consisting of untreated controls. The parameters taken into account at baseline (T0) and after 30d (T1) of therapy were: conjunctival hyperemia, lacrimal function tests [Schirmer I test and break up time (BUT)] and intraocular pressure (IOP). Conjunctival hyperemia showed a substantial improvement in both treated groups (P<0.001) but not among controls. Similarly, lacrimal function tests displayed an improvement of Schirmer I test in both treated groups (P<0.05) and an extension of BUT only in the group treated with 0.1% TSA (P<0.05). The IOP increase was statistically significant only in those patients treated with 0.1% TCB (P<0.001). The 0.1% TSA has proved to be an effective anti-inflammatory treatment of blepharoconjunctivitis affecting glaucoma patients on therapy with TPAs, leading to a sizeable decrease of inflammation as well as both quantitative and qualitative improvement of tear film. Furthermore, differently from 0.1% TCB, it does not induce any significant IOP increase.

Prostaglandin analogue drops for the treatment of soft tissue expansion and exophthalmos in patients with inactive thyroid eye disease

Thyroid eye disease (TED) is characterized by an inflammatory response leading to soft tissue expansion within the bony orbit, which may cause exophthalmos. Studies of glaucoma patients reported periorbital fat atrophy after treatment with prostaglandin analogue drops. We hypothesize that owing to this side effect, prostaglandin analogue drops may benefit patients with TED-induced exophthalmos. Interventional prospective pilot study. Five adults with inactive TED and exophthalmos treated with a single daily drop of bimatoprost to both eyes for 6 months. The effect of treatment was evaluated by clinical examinations, Hertel exophthalmometry, marginal reflex distance (MRD), and comparison of digital photographs from before and after treatment by 3 masked oculoplastic surgeons. Patients' subjective satisfaction was recorded as well. Hertel exophthalmometry showed an improvement in exophthalmos after treatment in 3 patients and no change in 2. Both MRD1 and MRD2 increased (for MRD2 p = 0.007). Two observers correctly identified the photograph taken after treatment in 4 patients, and the third observer correctly identified 2 patients and was indecisive about the others. Four patients reported an improvement in their appearance, although additional eyelid retraction was observed. Adverse effects were minimal. Topical prostaglandin analogue treatment of TED-associated exophthalmos appears safe. Although this pilot study was statistically underpowered to show positive results, our findings suggest a treatment-related reduction in periorbital fat volume in most cases and a subjective improvement in appearance. These findings have potential implications for the treatment of exophthalmos in the clinical setting, but more research is required.

Effect of a punctal plug on ocular surface disease in patients using topical prostaglandin analogues: A randomized controlled trial —Response

IMPORTANCE Ocular surface disease (OSD) is common and can reduce treatment compliance and quality of life. BACKGROUND To determine whether a punctal plug improves OSD and reduces intraocular pressure (IOP) in patients using prostaglandin analogue monotherapy. DESIGN Randomized controlled trial. PARTICIPANTS Sixty eligible subjects aged >18 years with symptomatic OSD from glaucoma clinics were invited to participate. Lacrimal or glaucoma surgery, lid malposition and contact lens wear were exclusion criteria. METHODS One eye received an inferior punctal plug, leaving the fellow eye as a control. MAIN OUTCOME MEASURES Ocular surface disease index (OSDI), tear film breakup time (TF-BUT), Oxford cornea score, tear osmolarity and IOP were compared at baseline and 6 weeks by masked investigators. RESULTS From 60 eligible, 48 (80.0%) participated (mean age 69.6 years; 60.0% female). OSDI reduced following plug insertion (mean difference [MD] 14.5, 95% confidence interval [CI] 5.06-23.94, P < 0.001). Compared to control eyes, in eyes receiving plugs the TF-BUT increased (MD 2.3 s, 95% CI 1.4-3.2, P < 0.001), the Oxford cornea score decreased (MD 0.5, 95% CI 0.3-0.7, P < 0.001), and tear osmolarity decreased (MD 10 mOsm/L, 95% CI 3.5-16.5, P = 0.003). Punctal plugs resulted in a significantly lowered IOP (MD 1.5 mmHg, 95% CI 0.1-2.9, P = 0.032). Sub-group analyses showed similar efficacy regardless of prostaglandin preservative status or lubricant drop use. Plugs were well tolerated but extrusion occurred in 8.5%, and epiphora increased in 6.5% eyes. CONCLUSIONS AND RELEVANCE Punctal plug insertion improves subjective and objective measures of OSD and results in a reduced IOP in patients with symptomatic ocular surface disease using prostaglandin analogue monotherapy.

Drug-induced uveitis.

Nearly one-half of all uveitis cases seen at tertiary referral centers have no identifiable cause. Many systemic, paraocular, intraocular, topical medications, and even vaccines can induce intraocular inflammation, scleritis, and rarely orbititis and are often overlooked as causes of uveitis. This review was undertaken to elucidate the strength of association of these medications with uveitis and to make clinicians aware of these associations, especially among newer medications. Medication-induced uveitis has become particularly important and more frequently seen because of the advent of biologic therapies such as immune checkpoint inhibitors (ICPIs), BRAF, and MEK inhibitors, antivascular endothelial growth factor agents, and antitumor necrosis factor agents, as well as newer systemic bisphosphonates are strongly associated with uveitis. The ever-broadening scope of pharmaceuticals now available to treat previously untreatable conditions, such as advanced metastatic cutaneous melanoma, have resulted in unintended ocular inflammatory diseases. Ophthalmologists must recognize that drugs such as ICPIs, BRAF, and MEK inhibitors, anti-vascular endothelial growth factor agents, tumor necrosis factor-α inhibitors, cidofovir, bisphosphonates, topical prostaglandin analogues, topical brimonidine, BCG vaccination can cause of uveitis. Utilizing a thorough review of systems, physicians may readily identify medications that may cause uveitis and avoid expensive and unnecessary laboratory testing.

Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose.

BackgroundTopical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30–50 µL drops that greatly exceed the physiologic 7-µL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect.MethodsBoth eyes (N=60) of 30 healthy volunteers received single 8-µL microdoses of 0.005% latanoprost (0.4 µg; µRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after µRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence.ResultsµRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs.ConclusionMicrodosing of 0.4 µg of µRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma.

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment Study

The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. Multicenter, randomized, triple-masked, placebo-controlled trial. Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n= 182 and n= 168 patients from the treatment and placebo groups, respectively). In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n= 272) and those with glaucomatous progression (n=78), as determined by visual field change (primary outcome), were assessed. PROMs on health-related and vision-related quality of life. Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P= 0.98; EQ-5D visual analog scale, P= 0.88; SF-36, P= 0.94, GQL-15, P= 0.66; GAL-9, P= 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P= 0.02; GAL-9, P= 0.02), but not on general health PROMs (EQ-5D, P= 0.62; EQ-5D visual analog scale, P= 0.23; SF-36, P= 0.65). Average change in PROMs on health-related and vision-related quality of life was similar forthe treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to functionasprimary end points in clinical trials when participants have newly diagnosed early-stage glaucoma.

Washout Duration of Prostaglandin Analogues: A Systematic Review and Meta-analysis.

Topic Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering effects in full responders are known to be 25–33% for this class; however, partial responders and nonresponders do exist. In clinical trials or prospective series, discontinuation and washout of PGAs is necessary to evaluate true change in IOP from novel surgeries and medical therapies. Clinical Relevance To identify all relevant papers with pertinent data on washout of PGAs and quantify the duration and long-term effect of reported PGA washout periods in glaucoma and OHT patients. Methods A systematic review and meta-analysis was conducted to investigate the long-term effects on IOP after discontinuation of topical PGAs POAG and OHT patients. The main search was conducted in MEDLINE/PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, and BIOSIS Previews and conference proceedings. Results 1055 papers were identified, 548 were independently screened by two physicians., and 56 papers were analyzed for washout durations. The mean washout was found to be 4.56 weeks (±1.25), with the mode and median being 5 weeks. Five studies were analyzed as randomized control trials in which latanoprost was discontinued for 4 weeks prior to restarting another intraocular pressure-lowering drug. Meta-analysis revealed a 4-week discontinuation of latanoprost, on average, subjects returned to their baseline IOP. Conclusion A significant IOP-lowering effect of latanoprost was not observed beyond 4 weeks, suggesting this may be an appropriate washout period for latanoprost. We could not identify appropriate washout periods for either travoprost or bimatoprost, although a majority of articles had 4-week washout durations for the two drugs. Despite the widespread use of this class of medication, there is a paucity of literature on the effects of PGA washout in patients that are treatment naïve to other topical medications.

The Effect of Prostaglandin Analogues on the Ciliary Zonular Fibers of the Rabbit Crystalline Lens

ABSTRACTPurpose: To evaluate the influence of prostaglandin (PG) analogues on the ciliary zonular fibers of the crystalline lens using scanning electron microscopy (SEM) of rabbit eyes, and to measure the matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) levels of the aqueous humor and crystalline lens treated with topical PG analoguesMethods: Fifty eyes from 25 New Zealand white rabbits were divided into five groups of five rabbits each. In the control group, balanced salt solution was administered via the topical route once a day to the eyes. The benzalkonium chloride (BAC) group was treated with 0.02% BAC, the Latanoprost group with 0.005% latanoprost, the Travoprost group with 0.004% Travoprost, and the Bimatoprost group with 0.03% Bimatoprost for 10 months. We examined the ciliary zonular fibers using SEM. We also measured the MMP and TIMP levels of the aqueous humor and crystalline lens.Results: SEM revealed some splitting of zonular fibers in eyes treated with topical PG analogues when compared with the control and BAC groups. The MMP-1 and TIMP-1 levels after treatment with the PG analogues did not differ significantly from the control and BAC groups (P > 0.05). There was no significant difference in MMP-1, MMP-3, TIMP-1, and MMP-1/TIMP-1 levels in the lens among all five groups.Conclusions: PG analogues may induce zonular change in rabbits microscopically. There was no association between zonular changes and the levels of certain types of MMP or TIMP in the aqueous humor or crystalline lens after topical treatment with PG analogues.

Effect of a punctal plug on ocular surface disease in patients using topical prostaglandin analogues: a randomized controlled trial.

Ocular surface disease (OSD) is common and can reduce treatment compliance and quality of life. To determine whether a punctal plug improves OSD and reduces intraocular pressure (IOP) in patients using prostaglandin analogue monotherapy. Randomized controlled trial. Sixty eligible subjects aged >18 years with symptomatic OSD from glaucoma clinics were invited to participate. Lacrimal or glaucoma surgery, lid malposition and contact lens wear were exclusion criteria. One eye received an inferior punctal plug, leaving the fellow eye as a control. Ocular surface disease index (OSDI), tear film breakup time (TF-BUT), Oxford cornea score, tear osmolarity and IOP were compared at baseline and 6 weeks by masked investigators. From 60 eligible, 48 (80.0%) participated (mean age 69.6 years; 60.0% female). OSDI reduced following plug insertion (mean difference [MD] 14.5, 95% confidence interval [CI] 5.06-23.94, P < 0.001). Compared to control eyes, in eyes receiving plugs the TF-BUT increased (MD 2.3 s, 95% CI 1.4-3.2, P < 0.001), the Oxford cornea score decreased (MD 0.5, 95% CI 0.3-0.7, P < 0.001), and tear osmolarity decreased (MD 10 mOsm/L, 95% CI 3.5-16.5, P = 0.003). Punctal plugs resulted in a significantly lowered IOP (MD 1.5 mmHg, 95% CI 0.1-2.9, P = 0.032). Sub-group analyses showed similar efficacy regardless of prostaglandin preservative status or lubricant drop use. Plugs were well tolerated but extrusion occurred in 8.5%, and epiphora increased in 6.5% eyes. Punctal plug insertion improves subjective and objective measures of OSD and results in a reduced IOP in patients with symptomatic ocular surface disease using prostaglandin analogue monotherapy.

Effectiveness and safety of switching from prostaglandin analog monotherapy to prostaglandin/timolol fixed combination therapy or adding ripasudil.

To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy. An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined. The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group. Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

Pretarsal skin height changes in children receiving topical prostaglandin analogue therapy for primary congenital glaucoma

To compare pretarsal skin height (PTSH), as proxy indicator of deepening of the upper eyelid sulcus, in children with primary congenital glaucoma (PCG) treated with topical prostaglandin analogues (PGAs) with PTSH in healthy children (control group 1) and children with PCG but not using PGAs (control group 2). We recruited children with PCG who had been using PGAs for at least 6months (PCG/PGA group). PTSH in all participants was measured using ImageJ software from photographs taken in a standardized manner. The PTSH was compared for the PCG group and both control groups. A total of 34 children with PCG and 41 controls (31 in group 1; 10 in group 2) were included. The difference in PTSH between children in the PCG/PGA group and both control groups was statistically significant (mean difference, ≥1.7mm [P<0.01]). The PTSH was significantly greater in children with PCG using PGAs compared to children with PCG not using PGAs and healthy children. Children and their parents should be counseled about lid abnormalities prior to commencing treatment with PGAs.