Intraocular pressure reduction with once-a-day application of a new prostaglandin eye drop: a pilot placebo-controlled study in 12 patients.

PURPOSE: To assess the ocular hypotensive effect of 15-keto fluprostenol, the oxidized metabolite of travoprost, on glaucoma patients, through a randomized double-masked placebo-controlled study. METHODS: Twelve patients with ocular normal tension glaucoma (NTG) (intraocular pressure [IOP] < 22 mmHg) were enrolled. In order to ensure patient compliance to treatment, all study subjects were hospitalized. In each patient, the eye to be submitted to the treatments was randomly chosen. After hospital admission (day 1), those patients received for 5 days at 8 P.M. either one drop of 15-keto fluprostenol (35 µg/ml) or one drop of placebo. IOP evaluation was performed within 8 A.M. and 8 P.M. for 6 days. Furthermore, we performed a determination of cardiovascular parameters before and after the treatments. RESULTS: Starting with the first IOP measurement after the first treatment (8 A.M. on day 2), IOP was reduced of about 14% in the eyes treated 15-keto fluprostenol, in comparison with baseline IOP values of 15-keto fluprostenol-treated patients. The IOP reduction in the 15-keto fluprostenol-treated group was significantly compared to placebo group (p < 0.05) starting from day 3 till day 6 of the study. Except for mild hyperemia in one 15-keto fluprostenol-treated eye, no other side effects were observed or reported by the enrolled patients. CONCLUSIONS: The travoprost metabolite 15-keto fluprostenol was effective in decrease IOP and maintained IOP reduction along 5 days of treatment. The 15-keto fluprostenol can be developed as a good candidate for once-a-day NTG patients' treatment.

Ocular surface status in glaucoma and ocular hypertension patients with existing corneal disorders switched from latanoprost 0.005% to tafluprost 0.0015%: comparison of two prostaglandin analogues with different concentrations of benzalkonium chloride.

IMPORTANCE: Glaucoma treatment has often been associated with adverse side-effects from preservatives that are included in the used eye drops. BACKGROUND: To evaluate changes in the ocular surface and the presence of prostaglandin-induced corneal disorders after being switched from latanoprost 0.005% to low preservative tafluprost 0.0015% ophthalmic solution. DESIGN: Single centre, prospective study. PARTICIPANTS: Patients with primary open-angle glaucoma or ocular hypertension that had received treatment with once daily latanoprost 0.005% ophthalmic solution for control of intraocular pressure (IOP) for 3 months, with a score of above 1 on the National Eye Institute (NEI) ocular surface staining scale. METHODS: Following the ≥3 month latanoprost treatment period, patients were switched to once daily low preservative tafluprost 0.0015% ophthalmic solution. Patients were followed for a minimum of 3 months. MAIN OUTCOME MEASURES: Ocular surface changes were assessed by fluorescein staining score (NEI scale). Additional evaluations included tear break-up time, hyperaemia score, subjective symptoms, changes in intraocular pressure and presence of adverse reactions. RESULTS: Out of 59 patients enrolled, 51 were included in the final analysis. Fluorescein staining scores at baseline, prior to treatment switch, were 6.9 ± 3.1 and 3.3 ± 2.7 at the end of the study period (change in scores was -3.6 ± 2.2 [P < 0.001]). At last follow-up, significant improvements were observed in tear break-up time, hyperaemia score and subjective symptoms (all P < 0.05). CONCLUSIONS AND RELEVANCE: The clinical signs of ocular surface disease and subjective symptoms of dry eyes improved following the switch to low preservative tafluprost and demonstrated comparable IOP lowering effectiveness.

The efficacy and safety of bimatoprost/timolol maleate, latanoprost/timolol maleate, and travoprost/timolol maleate fixed combinations on 24-h IOP.

PURPOSE: To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma. METHODS: This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared. RESULTS: Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P < 0.05). CONCLUSION: All three fixed combinations effectively controlled IOP for 24-h and had a similar effect on diurnal and nocturnal IOP variations.

Topical medication instillation techniques for glaucoma.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops. OBJECTIVES: To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane. MAIN RESULTS: We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months. AUTHORS' CONCLUSIONS: Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.

Periorbital changes associated with prostaglandin analogs in Korean patients.

BACKGROUND: Prostaglandin analogs (PGAs) are commonly used to treat glaucoma because of their powerful intraocular pressure lowering effect. However, various periorbital changes associated with the use of PGAs have been reported. We investigated the incidence of periorbital changes in Korean patients who were treated with PGAs, and analyzed clinical factors associated with superior sulcus deepening. METHODS: This study included 58 glaucoma patients who were treated with latanoprost, travoprost, or bimatoprost unilaterally. Face photographs were collected, and periorbital changes such as superior sulcus deepening, eyelid pigmentation, ptosis, lid retraction, dermatochalasis, and redness were evaluated by two oculoplastic specialists. For each patient, the contralateral eye served as a control. The frequency of ptosis, dermatochalasis, pigmentation, erythema, and superior sulcus deepening were analyzed. Demographic and ocular factors were compared between patients who showed superior sulcus deepening and those who did not. RESULTS: Thirty-one patients (53.4%) showed one or more periorbital changes associated with PGAs. The most common change was superior sulcus deepening (24.1%), followed by eyelid pigmentation (19.0%), eyelid erythema (19.0%), dermatochalasis (10.3%), eyelid retraction (5.2%), and ptosis (3.4%). The age of the patient and the duration of PGA administration was significantly correlated with superior sulcus deepening (p = 0.007, p = 0.002, respectively). CONCLUSIONS: Periorbital changes are frequently seen in patients who use PGAs, and superior sulcus deepening is the most common change in Korean patients. Long-term use of PGAs and old age were associated with superior sulcus deepening.

Effect of topical ophthalmic latanoprost 0.005% solution alone and in combination with diclofenac 0.1% solution in healthy horses: a pilot study.

OBJECTIVE: To evaluate the effect of topical ophthalmic 0.005% latanoprost alone and in combination with 0.1% diclofenac on healthy horses. ANIMALS STUDIED: Twelve healthy adult horses. PROCEDURES: A randomized, masked crossover design was used with horses divided into three groups for once daily treatment in one randomly selected eye. For arm 1 of the study, Group D (n = 3) received 0.1% diclofenac, Group L (n = 3) received 0.005% latanoprost, and Group DL (n = 6) received 0.005% latanoprost and 0.2 ml of 0.1% diclofenac. For arm 2 of the study, horses from Group D and L were placed into Group DL and horses from Group DL were placed into either Group D or L. Evaluations of intraocular pressure (IOP), vertical pupil diameter, aqueous flare, conjunctival hyperemia, epiphora, blepharospasm, and blepharoedema were performed 4 times daily on days 1 and 2 (baseline), days 3 to 7 (arm 1 treatment), days 8 to 11 (washout), days 12 to 16 (arm 2 treatment), and days 17 and 18 (return to baseline). RESULTS: During the treatment period, significant reduction in IOP and vertical pupil diameter occurred in treated eyes of Groups L and DL, but not Group D. These variables did not differ significantly between Groups L and DL. Blepharospasm, blepharoedema, epiphora, and conjunctival hyperemia scores were significantly higher in Group L than in Groups D and DL. CONCLUSIONS: Latanoprost reduced IOP in healthy horses and signs of drug-induced discomfort were mitigated by concurrent use of diclofenac.

Effect of prophylactic topical hypotensive medications in reducing the incidence of postoperative ocular hypertension after phacoemulsification in dogs.

OBJECTIVE: To determine whether topical hypotensive medications prevent postoperative ocular hypertension (POH) after phacoemulsification. ANIMALS STUDIED: 52 client-owned dogs (88 eyes). PROCEDURES: Diabetic and nondiabetic dogs having undergone phacoemulsification were included in this retrospective study. The control group received no ocular hypotensive medications. The treatment groups received latanoprost, dorzolamide, or dorzolamide/timolol, beginning immediately after surgery, for 2-week duration. IOPs were obtained at initial examination followed by 4 h, 24 h, 7 days, and 14 days postoperatively. POH was defined as an IOP above 20 mmHg (POH20) or 25 mmHg (POH25). RESULTS: POH20 occurred in 33 of 87 eyes (37.93%), including 11 of 21 eyes (52.38%) in the control group, three of 23 eyes (13.04%) in the latanoprost group, eight of 15 eyes (53.33%) in the dorzolamide group, and 11 of 28 eyes (39.29%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.11). POH25 occurred in 22 of 86 eyes (25.58%), including seven of 21 eyes (33.33%) in the control group, two of 23 eyes (8.70%) in the latanoprost group, five of 15 eyes (33.33%) in the dorzolamide group, and eight of 27 eyes (29.63%) in the dorzolamide/timolol group. Active treatment groups were compared to the control group, and the overall group effect was not significant (P = 0.31). Intraoperative use of intracameral tissue plasminogen activator significantly decreased the chances of POH25 (P = 0.0063). CONCLUSIONS AND CLINICAL RELEVANCE: The latanoprost group had a substantially lower percentage of POH 20 and POH25 compared to the control and other active treatment groups, although statistical significance was not achieved. Intraoperative intracameral tissue plasminogen activator decreased the incidence of POH25.

Evaluation of physical properties and dose equivalency of generic versus branded latanoprost formulations.

The purpose of this study was to comparatively evaluate the pharmaceutical characteristics of various marketed generic formulations of prostaglandin analogue latanoprost in the Indian market. Three generics of latanoprost and one branded (Xalatan) formulation (five vials each) were obtained from authorized agents from the respective commercial sourcing having the same batch number. These formulations were coded, and the labels were removed. At a standardized room temperature of 25 °C, the concentration, osmolarity, drop size, pH, and total drops per vial were determined for Xalatan and all the generics of latanoprost. The concentration of various brands varied between 50.49 ± 0.36 and 58.90 ± 0.52 µg/ml as compared to the standard labeled concentration of 50 µg/ml on the latanoprost vials. The concentration of drugs in individual drop varied from 1.30 ± 0.05 to 1.78 ± 0.04 µg/drop. The volume of drug formulation per bottle varied from 2.4 ± 0.12 to 2.6 ± 0.09 ml/bottle. The number of drops per bottle varied from minimum of 88.60 ± 0.10 drops to maximum of 102.0 ± 4.3 drops across all the formulations, while the drop size varied from 25.72 ± 2.70 to 29.97 ± 1.38 µl. The osmolarity of 2/4 drugs was within 300 mOs M (±10 %). The specific gravity varied between 0.98 ± 0.01 and 1.007 ± 0.01, while pH was between 7.05 ± 0.004 and 7.13 ± 0.005. Two of the generic brands were outside the United States pharmacopoeia limits (±10%) for ophthalmic formulation, with concentration exceeding the limits by 3 % (p = 0.151) and 8 % (p = 0.008), respectively. This pilot study highlights that there are significant variations in the drug concentrations and physical properties of generic latanoprost formulations. Although none of the brands had concentrations below the recommended level, two of the brands had concentrations exceeding the limits by 3 and 8 %, respectively.

Does the intraocular pressure-lowering effect of prostaglandin analogues continue over the long term?

The purpose of the study is to assess the changes in the long-term effects of prostaglandin analogues (PGAs) on intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG). Data of POAG patients treated with latanoprost (0.005 %), travoprost (0.004 %), or bimatoprost (0.03 %) as the first line treatment for 5 years or more were retrospectively evaluated. Baseline ophthalmic assessment values were recorded together with the IOP at the 6th month, 1st year, and then annually. The 79 patients included 33 (41.8 %) men and 46 (58.2 %) women. There were 34 (43.0 %) patients using latanoprost (0.005 %), 23 (29.1 %) patients using bimatoprost (0.03 %), and 22 (27.8 %) patients using travoprost (0.004 %). There was no difference between the groups in terms of age, gender, or baseline IOP levels. IOP levels at the 6th month were significantly lower than baseline IOP levels in all groups (p < 0.01, Friedman test). The IOP decrease was maintained after the 6th month in all three group with no statistically significant difference compared to the 6th month IOP value (p > 0.05, Friedman test) and no statistically significant difference between the groups during follow-up (Kruskal-Wallis test, p > 0.05). IOP reductions with PGAs were adequate and stable in the 5-year follow-up period with no decrease in effectiveness over time.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB.

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management.

Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5.

The combination of timolol and latanoprost, which are ocular hypotensive agents, has a greater ocular hypotensive effect than each as monotherapy. However, the protective effect of the combination is not well understood. In the present study, we investigated whether latanoprost/timolol in combination has an additive or synergistic cytoprotective effect on neuro retinal cells (RGC-5). To investigate the protective effects of timolol/latanoprost in combination, cultured RGC-5 were treated with various concentrations of these two agents, singly or together, after which the cells were exposed to oxidative stress, serum deprivation, or endoplasmic reticulum (ER) stress in vitro. Cells were also treated with an Akt inhibitor, LY294002, to examine the mechanism of the protective effect. Latanoprost, timolol, and the two in combination reduced cell death induced by oxidative stress, serum deprivation, or ER stress. The latanoprost/timolol combination reduced cell death to a greater extent than monotherapy with latanoprost or timolol on serum deprivation only, and LY294002 inhibited the protective effect of their combination. These findings suggest that timolol/latanoprost in combination have a protective effect against serum deprivation only by activation of Akt signaling. Furthermore, this combination has not only an ocular hypotensive effect but also a neuroprotective effect.

Interaction with therapeutic soft contact lenses affects the intraocular efficacy of tropicamide and latanoprost in dogs.

Therapeutic soft contact lenses (TSCLs) are frequently used to support or protect the cornea during healing. Our aim was to quantitatively evaluate the efficacy of topical medications in TSCL-fitted dogs and determine whether it is affected by the presence of TSCLs. In Phase I, pupil diameter was measured in eyes treated with tropicamide and in eyes covered with TSCLs and then treated with tropicamide, with 1-week intervals between sessions. In Phase II, intraocular pressure (IOP) was measured in uncovered and TSCL-covered eyes treated with latanoprost, with 1-week intervals between sessions. Tropicamide caused significant mydriasis in both uncovered and TSCL-covered eyes (P = 0.005). On the other hand, latanoprost caused a significant decrease in IOP when applied to uncovered eyes (P = 0.002), but had no significant effect on IOP when applied to TSCL-covered eyes (P = 0.7). As we used the same dogs and identical TSCLs throughout the study, we conclude that the different outcomes of the two drugs are due to properties of the drugs themselves, or their formulations, affecting their interaction with the TSCLs. The clinical efficacy of topical drugs applied to TSCL-covered eyes may have to be determined for each drug and/or formulation.

[Prostaglandin analogues in glaucoma treatment]. / Analogi prostaglandinov v lechenii glaukomy.

AIM: to evaluate the effectiveness of prolatan (latanoprost 0.005%) in the treatment of primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 35 POAG patients (41 eyes) aged 55-72 years, of them 20 men and 15 women. The patients were randomized into two groups followed up for 3 months. Group 1 consisted of 17 patients (19 eyes) who received prolatan once daily in the evening. Group 2 consisted of 18 patients (22 eyes) under Xalatan 0.005% once daily in the evening. RESULTS: The true intraocular pressure (IOP) decreased by the average of 28.6%. Analysis of perimetry results showed a statistically reliable increase in the MD - by 17.4% in the study group and by 20% in the control group, and PSD indices - by 10.7% and 11.9%, respectively. Optical coherence tomography revealed an improvement of optic disc parameters in both groups. In particular, the cup volume decreased reliably by 8.4% and 6.3% and cup area - by 24.4% and 28.5%, respectively, while the rim area increased by 20.8% and 17.9%, respectively. The patients complained of neither burning, nor discomfort, nor foreign body sensation after prolatan instillations. We also report the absence of side effects. CONCLUSION: The study has proved high antihypertensive effectiveness of prolatan. Improved morphometric parameters of the optic disc (decreased cup volume and area, increased rim area) indirectly indicate the neuroprotective potential of the drug. Being well-tolerated by the patients, prolatan can be recommended as the first choice treatment of glaucoma.

Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes.

Prostaglandin F2α analogs, commonly prescribed for glaucoma treatment, have been shown to induce side effects such as cutaneous hypertrichosis and hyperpigmentation. Therefore, these medications have theoretic applications in the treatment of alopecia and disorders of hypopigmentation. We reviewed the literature to find original studies assessing the use of prostaglandin F2α analogs in these settings. Studies and reports were analyzed in regards to androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring. Based on the results of these studies, and consideration of pathophysiologic mechanism, the most promising applications for prostaglandin F2α analogs include androgenic alopecia, chemotherapy-induced alopecia, and alopecia areata concurrently treated with corticosteroids.

Efficacy of prophylactic antiglaucoma and anti-inflammatory medications in canine primary angle-closure glaucoma: a multicenter retrospective study (2004-2012).

PURPOSE: To evaluate long-term efficacy of antiglaucoma medications with or without combined topical anti-inflammatory treatment in preventing increased intraocular pressure and clinical signs of glaucoma in eyes considered at risk of the development of the disease. METHODS: Retrospective analysis identified 88 canine patients presenting with unilateral acute congestive primary angle-closure glaucoma (IOP > 25 mm Hg) and gonioscopic findings of pectinate ligament dysplasia and/or narrow or closed iridocorneal angle in the contralateral nonglaucomatous eye. Patients with histopathologic confirmation of pectinate ligament dysplasia or angle closure in the initial glaucomatous eye receiving prophylactic medical therapy in the contralateral eye were included. Time to medical failure for each antiglaucoma medication and efficacy of the combination therapy were evaluated. RESULTS: The most commonly affected pure-breds were the American Cocker Spaniel (20.4%) and Basset Hound (11.36%). The patients receiving demecarium bromide 0.125% had the longest estimated median time to medical failure at 330.0 days, followed by latanoprost 0.005%, dorzolamide hydrochloride 2.0%, and demecarium bromide 0.25% at 284.0 days, 272.5 days, and 143.0 days, respectively. The estimated median time to medical failure for patients receiving topical antiglaucoma and anti-inflammatory medication was 324.0 days versus 195.0 days in patients receiving antiglaucoma medication alone. Survival analysis showed no statistical significance. CONCLUSIONS: None of the four antiglaucoma medications evaluated statistically delayed medical failure when compared to each other. Although significance was not achieved, our data suggest that adjunctive use of topical anti-inflammatory medications may be beneficial in these cases.

Latanoprost is effective in reducing high intraocular pressure associated with Graves' ophthalmopathy.

PURPOSE: To assess the efficacy and tolerability of latanoprost in the treatment of glaucoma and ocular hypertension associated with Graves' ophthalmopathy. Prospective interventional case series. MATERIALS AND METHODS: 28 patients (19 females and 9 males) aged from 31 to 68 (mean age 45.5 +/- 5.6), presenting with diagnosis of Graves' ophthalmopathy and intraocular pressure equal to 25.0 mmHg or more. 18 Patients presented with inflammatory stage of Graves' ophthalmopathy. 22 patients were within the first two years from the onset of symptoms of Graves' ophthalmopathy. 6 patients had exophthalmos and history of active Graves' ophthalmopathy. Intraocular pressure was measured before treatment, and at two, four and six weeks of treatment with latanoprost at 9 am. Ocular symptoms and signs were noted before and after the treatment period. RESULTS: The mean baseline intraocular pressure was 26.6 +/- 2.5 mmHg, ranging from 25.0 mmHg to 42 mmHg. In two weeks of treatment, the mean intraocular pressure was 18.6 +/- 2.3 mmHg (min 12.0 mmHg, max 27.0 mmHg). At 4 weeks mean intraocular pressure was 18.4 +/- 2.2 mmHg (min 11.0 mmHg, max 28.0 mmHg). At 6 weeks mean intraocular pressure was 18.7 +/- 1.9 mmHg (ranging from 11 mmHg to 25.0 mmHg). 3 patients experienced mild side effects. CONCLUSIONS: Latanoprost is effective and well tolerated in the treatment of increased intraocular pressure associated with Graves' ophthalmopathy.

Biodegradable nanoparticles for controlled subconjunctival delivery of latanoprost acid: in vitro and in vivo evaluation. Preliminary results.

Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, ζ-potential, drug entrapment efficiency and LA release. LA-loaded NPs (equivalent to 8.5 µg LA) were administered into the subconjunctival space of normotensive rabbits (group A). A free LA solution of the same drug content was subconjunctivally injected in a second rabbit group (group B), while blank NPs were administered in a third group (group C). A group of untreated animals (group D) served as the control. Intraocular pressure (IOP) was monitored for 8 consecutive days, using the Tono-pen XL. Aqueous humor (AH) levels of LA were evaluated for 6 days post-administration, by means of HPLC. Mean nanoparticle size was 80 nm. The drug entrapment efficiency was 18.3%. NPs sustained the release of LA over several days in vitro. Non-significant differences in baseline IOP were found between groups (p = 0.22). LA-loaded NPs exerted a significant hypotensive effect on group A, while IOP values remained significantly lower compared to the rest groups, throughout the study (p = 0.04). LA AH concentrations in group B continuously decreased with time, while LA levels in group A steadily increased. On day 6, LA levels were higher in group A compared to group B (344 ± 73.5 ng/ml and 228 ± 41.01 ng/ml, respectively). No adverse effects were observed. In conclusion, after subconjunctival administration, the LA-loaded NPs provided sustained LA delivery in vivo. They appear to be a promising system for the controlled subconjunctival delivery of LA.

The effect of topical latanoprost on anterior segment anatomic relationships in normal dogs.

OBJECTIVE: Topical latanoprost 0.005% is commonly used in dogs with primary angle closure glaucoma (PACG), and marked miosis has been reported in the literature. To further explore the effect of topical latanoprost on anterior segment anatomy, we performed iridocorneal angle biometrics in normal beagle dogs. METHODS: Thirty-five normal female beagle dogs were assessed using anterior segment optical coherence tomography (AS-OCT). One eye of each dog was scanned with the AS-OCT in the superotemporal quadrant. One drop of latanoprost 0.005% was applied topically, and the OCT scan was repeated 30 min later. Images were imported into ImageJ, and pupil diameter, anterior chamber angle, angle opening distance, angle recess area (ARA), anterior chamber hemifield, and anterior chamber depth were measured. RESULTS: A single drop of latanoprost resulted in marked miosis, anterior bowing of the peripheral iris, narrowing of the iridocorneal angle, and shallowing of the anterior chamber. The anterior segment parameters demonstrated a significant reduction (P-value ≤ 0.001) from baseline following latanoprost with the exception of the ARA (P = 0.07). CONCLUSIONS: Latanoprost significantly decreases pupil diameter and narrows the iridocorneal angle in normal female beagle dogs. Therefore, the utility of latanoprost as a prophylactic treatment for PACG in fellow eyes may be limited. Studies using quantitative iridocorneal angle measurements in goniodysgenic dogs are warranted to understand the changes in iridocorneal angle morphology that occur in PACG in response to topical application of latanoprost.