BACKGROUND: The treatment of vitiligo is a persistent challenge in dermatology. New treatments are being offered and studied in this field for those resistant to or intolerant of classical therapies.
OBJECTIVE: In this systematic review, we study the use of prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) in the treatment of vitiligo, as they are known for their pigmentation inducing effects through activating melanocytes.
METHODS: We searched four main online databases with the keywords \"Vitiligo\", \"Prostaglandin analogue\" and \"Phosphodiesterase inhibitor\".
RESULTS: A total of 42 articles were included, with 1027 cases, studying drugs like bimatoprost, latanoprost, travoprost, dinoprostone, apremilast, crisaborole, etc. Among the included studies, the treatment regimens are commonly once or twice daily for 12-48 weeks, with a mean of 20.61 weeks, and the routes of administration are mainly topical gels or ophthalmic solutions and oral tablets. Side effects are mild and tolerable, namely erythema, itching or burning sensations at application site for topicals, or gastrointestinal problems with apremilast. Repigmentation results are significant in both adult and pediatric patients and progressive or stable vitiligo. PGAs and PDEIs outperform many classical therapies, for example, narrowband ultraviolet B phototherapy (NB-UVB), tacrolimus, mometasone or methylprednisolone mini-pulse. PGAs or PDEIs are usually used in combination therapies to either cause synergism or increase drug delivery, and almost always enhance repigmentation, for example, with NB-UVB, fractional CO2 laser, microneedling, and mometasone.
CONCLUSIONS: Monotherapy or add-on PGAs and PDEIs can be considered effective treatments for vitiligo and promising last resorts for those resistant to other therapies.

BACKGROUND: Selective laser trabeculoplasty (SLT) emerges as a first-line treatment for newly diagnosed open-angle glaucoma and ocular hypertension. However, the interindividual response to SLT considerably varied. Large-scale clinical investigations concerning predictive factors for SLT effectiveness are limited. This study aimed to identify baseline predictors of the percentage intraocular pressure (IOP)-lowering effectiveness of SLT using an alternative mathematical approach.
METHODS: Mathematical equations of IOP under the steady state of aqueous humour flow were formulated. The conclusive equation integrates physiological variables, including trabecular outflow facility, uveoscleral outflow fraction, plasma protein concentration, albumin/globulin ratio, mean arterial pressure, episcleral venous pressure, and plasma osmolarity. The equation was employed to estimate the percentage of IOP reduction following SLT and subsequently subjected to global sensitivity analysis to determine significant predictors of the IOP-lowering effect of SLT using the Monte Carlo simulation of 8,192 samples.
RESULTS: In the current model, a 50% improvement in the trabecular outflow facility impacted by SLT is associated with a mean percentage IOP reduction of 16.6%. Lower baseline trabecular outflow facilities were the strongest predictors, showing a correlation with greater effectiveness of SLT in terms of percentage of IOP reduction. The second most influential factor includes baseline uveoscleral outflow fraction, followed by baseline episcleral venous pressure. Specifically, lower baseline uveoscleral outflow fraction and episcleral venous pressure were found to be correlated with increased effectiveness of SLT. Baseline levels of plasma protein concentration, albumin/globulin ratio, mean arterial pressure, and plasma osmolarity have minimal impact on SLT success or failure.
CONCLUSIONS: This study identifies baseline trabecular outflow facilities as the strongest predictor of SLT effectiveness. The results suggested that pre-SLT medical treatment that augments uveoscleral outflow and/or trabecular outflow facilities could compromise the effectiveness of subsequent SLT in terms of percentage IOP reduction compared to those who never received pre-SLT medication.

OBJECTIVE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC.
METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC.
RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not.
CONCLUSIONS: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.

OBJECTIVE: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications.
METHODS: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications.
RESULTS: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate (p = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant.
CONCLUSIONS: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay.

To report that the periorbital changes induced by prostaglandin analogue (PGA) eye drops are partially reversible after discontinuing treatment.
Nine patients with prostaglandin-associated periorbitopathy seen in a referral oculoplastic practice were included in this study, eight with unilateral glaucoma and one with bilateral open-angle glaucoma. All of them had been treated with topical PGA for at least one year, before the treatment was discontinued for cosmetic reasons.
In all cases, there were evident periocular differences between the treated eye and the fellow eye, consisting mainly of deepening of the upper eyelid sulcus and eyelid fat pad reduction. One year after discontinuing the PGA eye drops, improvement of these features was observed.
Clinicians and patients should be aware of the side effects of topical PGA therapy on periorbital tissues, and that these side effects can partially regress after discontinuation of the medication.

To investigate whether prostaglandin analogue (PGA) eyedrops have a significant effect on central corneal thickness (CCT), we conducted a systematic search of literature published from 2000 to 2021. Among the studies conducted on topical PGA therapy in open-angle glaucoma or ocular hypertension patients over 18 years old, prospective studies with CCT change as an outcome were included. A single-arm meta-analysis was conducted to assess the overall effect on CCT, and subgroup analysis according to exposure time of PGA eyedrops was also performed. We counted the number of articles that reported on severe events (CCT reduction of 25 μm or more) and obtained their proportion. The methodological quality was assessed by the McHarm tool. Twenty-two reports of prospective studies were selected. The results of the single-arm meta-analysis showed very high heterogeneity. Still, in subgroup analysis, when PGA was used for more than 6 months, heterogeneity was low, and a significant decrease in CCT was observed. Severe events were reported in two reports and occurred in 3.8% to 14.8% of participants. PGA eyedrop use may cause a clinically significant CCT decrease, requiring CCT follow-up.

The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products.

The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients\' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited.

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).
METHODS: Ten ophthalmologically normal Beagle dogs.
METHODS: 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.

BACKGROUND: To evaluate the effect of topical prostaglandin analogues on agreement of IOP measurements obtained by Goldmann applanation tonometry (GAT), rebound tonometry (RBT), and noncontact tonometry (NCT) in eyes with primary open- angle glaucoma (POAG).
METHODS: Intraocular pressure measurements were obtained using GAT, RBT, and NCT in patients with POAG with or without prostaglandin analogues. The agreement between each tonometry was analysed using Bland-Altman analyses in those with or without prostaglandin analogues. The effect of average IOP on IOP differences was also evaluated.
RESULTS: Among a total of 86 subjects included in the study, 44 patients were using prostaglandin analogues. The difference in IOP measured by GAT and RBT was marginally greater in those with (GAT-RBT: - 0.94 ± 1.63 mmHg) prostaglandin analogues than in those without (- 0.33 ± 1.22 mmHg, P = 0.06). The difference in IOP measured by GAT and NCT was significantly greater in the prostaglandin group (GAT-NCT: 2.40 ± 2.89 mmHg) than in the group without prostaglandin analogues (0.41 ± 1.63 mmHg, P < 0.01). While there was no significant relationship between the average of all tonometries and the difference between tonometries in those without prostaglandin analogues, both RBT and NCT underestimated IOP relative to GAT at higher IOP in those using prostaglandin analogues.
CONCLUSIONS: Intraocular pressure measured by RBT and NCT was similar to that measured by GAT in those without prostaglandin analogues. RBT overestimated and NCT underestimated IOP compared to GAT in those using prostaglandin analogues.