Puberty attainment and reproductive performance of yearling Bos indicus-influenced heifers after two sequential treatments with progesterone.

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P4) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen.

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.

15 keto fluprostenol isopropyl ester (80 µgr/mL) gel for cosmetic eyelash growth and enhancement.

BACKGROUND: Eyelashes have both a protective and an aesthetic function. Hypotrichosis of the eyelashes may negatively influence an individual's self-perception. OBJECTIVE: To evaluate efficacy and safety of topical administration of a new cosmetic preparation containing 15 keto fluprostenol isopropyl ester (80 µgr/mL) for the treatment of idiopathic hypotrichosis of the eyelashes. METHODS: This is a monocentric, double-blind, vehicle-controlled study. Forty patients (18 years) with idiopathic hypotrichosis (GEA 1 or 2), who also exhibit feelings of low confidence, based on the ESQ score, were divided into two groups. Group 1: twenty women treated with once-daily 15 keto fluprostenol isopropyl ester gel and Group 2: twenty women treated only with the vehicle gel. RESULTS: Group 1: The average difference in eyelash length measured at the midpoint of palpebral margins between T0 and T2 for Group 1 was 1633 mm and for Group B was 0.25 (P < 0.0001). Comparing the ESQ questionnaires of Groups 1 and 2 from T0 to T2, only the 80% of the patients of Group 1 declared to dedicate less time to the application of cosmetic mascara, having longer and darker lashes at T2 vs patients of Group 2, of which only 20% reported longer and darker eyelashes at T2. About safety, only one patient of Group 1 experienced sensation of ocular sensation heaviness and headache. No other side effects were referred. CONCLUSIONS: 15 keto fluprostenol isopropyl ester gel was effective in enhancing eyelash growth, with an excellent safety profile.

Effects of prostaglandin-mediated and cholinergic-mediated miosis on morphology of the ciliary cleft region in dogs.

OBJECTIVE To compare morphology of the ciliary cleft (CC) region in dogs after topical administration of latanoprost, pilocarpine, or a combination of latanoprost and pilocarpine. ANIMALS 6 Beagles. PROCEDURES A prospective 4-phase crossover study with washout periods was performed. Latanoprost (phase L), pilocarpine (phase P), pilocarpine followed by latanoprost (phase PL), and latanoprost followed by pilocarpine (phase LP) were administered to the right eye. Artificial tears were administered to the left eye (control eye). For each phase, pupil diameter and intraocular pressure (IOP) were measured and ultrasonographic biomicroscopy was performed 2 hours after topical treatment. Angle opening distance (AOD), ciliary cleft width (CCW), ciliary cleft length (CCL), and ciliary cleft area (CCA) were evaluated. RESULTS All treated eyes had marked miosis without significant differences in pupil diameter among phases. Significant IOP reductions were detected for all phases, except phase P. The AOD and CCA were significantly increased in all phases for treated eyes, compared with results for control eyes. The CCW was significantly increased in phases P, PL, and LP; CCL was significantly increased in phases PL and LP. Comparison of treated eyes among phases revealed that CCW differed significantly between phases L and P and between phases L and PL. CONCLUSIONS AND CLINICAL RELEVANCE Prostaglandin-mediated and cholinergic-mediated miosis caused variations in CC configurations. When latanoprost and pilocarpine were used in combination, the first drug administered determined the cleft morphology, which was not fully reversed by the second drug. The CC morphology did not fully explain IOP reductions.

Treatment merits of Latanoprost/Thymoquinone - Encapsulated liposome for glaucomatus rabbits.

Elevation of the intraocular pressure (IOP) is recognized as a risk factor for glaucoma development. Latanoprost (LAT) is a prostaglandin analog used to reduce the (IOP). Thymoquinone (TQ) is a major bioactive ingredient of Nigella sativa. The aim of this study was to develop novel liposomal drug carriers for ocular delivery of LAT, TQ and a mixture of them to investigate their IOP lowering efficacy upon subconjunctival injection in glaucoma-induced rabbit's eye. The aim of the present work extends also to study the effect of the different liposome formulations on the aqueous humor oxidative stress. Liposome samples were prepared using thin film hydration method. The physiochemical properties of the prepared drugs were characterized. The IOP was recorded for 70 rabbits using Schiotz-tonometer. Malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) activities and total antioxidant activity of the aqueous humor were estimated. Fourier transform infrared and differential scanning calorimetric studies confirmed the interaction between the drug and the vesicles, which resulted in high drug encapsulation efficiency ≥88%. The size of the prepared liposomes was less than 10 µm which make them suitable in ophthalmic applications. The sustained effect was achieved by liposome samples of Lip (LAT) and Lip (LAT + TQ) which were able to reduce the IOP significantly up to 84 h. Morever, the treatment of glaucomatous rabbits with liposome formulations containing TQ in their preparation [Lip (TQ) and Lip (LAT + TQ)] greatly improved the ocular tissue-induced histopathological lesions. None of the prepared liposome formulations succeeded to improve the glaucoma-induced oxidative stress damage.

Prospective study comparing Xalatan® eye drops and two similar generics as to the efficacy and safety profile.

PURPOSE: To evaluate the efficacy and safety between two generic prostaglandins Lataz-Xalaprost (Greece) and the corresponding original drops (Xalatan®). MATERIAL AND METHODS: In this prospective randomized study, 60 patients diagnosed with open-angle glaucoma or ocular hypertension were enrolled, who had never received antiglaucoma treatment. Subjects were divided randomly into three groups (Xalatan, Lataz, and Xalaprost groups) and they were studied over 16 weeks. At each visit, the mean applanation tonometry values and tear break-up time were measured. The Ocular Surface Disease Index questionnaire was used to evaluate patient's symptoms. RESULTS: There was a statistically significant difference (p < 0.001) in the mean values of the intraocular pressure between the baseline and the last visit (Xalatan group: from 23.11 ± 1.61 mmHg to 15.81 ± 1.22 mmHg, Lataz group: from 23.26 ± 1.33 mmHg to 15.80 ± 1.47 mmHg, and Xalaprost group: from 23.08 ± 1.45 mmHg to 16.08 ± 1.38 mmHg). Both generic eye drops showed mean percentage intraocular pressure reduction comparable to the standards of prostaglandin analogues (Xalatan: 31.57%, Lataz: 32.06%, and Xalaprost: 30.34%). Xalatan reduced the tear break-up time less, followed by Lataz and then by Xalaprost (Xalatan: from 8.5 to 8 s, Lataz: from 8.2 to 7.4 s, and Xalaprost: from 8.7 to 7.7 s). Xalatan presented the best safety profile, followed by Lataz and least was Xalaprost, according to Ocular Surface Disease Index questionnaire's results. CONCLUSION: No significant difference was recorded in the effectiveness of each generic prostaglandin compared to the original. Furthermore, no patient had to change medication. The differences that arose in the safety profile of the three eye drops suggest a prompt closer initial monitoring of patients who are administered generic eye drops.

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

PURPOSE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

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.

Effect of consecutive re-synchronization protocols on pregnancy rate in buffalo (Bubalus bubalis) heifers out of the breeding season.

The combined effect of six consecutive timed artificial inseminations (TAIs) on pregnancy rates, following two different synchronization protocols on buffalo heifers, over a period of seven months typically characterized by low breeding performances, were investigated in this study. A total of 2189 TAIs were performed on 1463 buffalo heifers within a large buffalo farm in the south of Italy. Individual animals were allowed to undergo synchronization protocol (either a slightly modified Ovsynch or Progesterone treatment) and TAI until establishment of pregnancy or else for not more than six consecutive times. Semen of seven proven bulls was used throughout the study, which was carried out from March to September of the same year. Therefore, other than the effect given by consecutive TAIs over time, a monthly and a seasonal effect could also be tested, once the entire period was split into a Low Breeding Season (LBS) from March to June, and a Transition to Breeding Season (TBS) from July to September. From the data recorded in this study and the statistical analysis performed, it can be stated that the two protocols for the synchronization of ovulation were similar in efficiency in determining pregnancies with an overall fertility rate of 89.4% when the comparison was run both on a monthly basis or when months were grouped into two different seasons. In addition, an average of 1.83 AI/pregnancy was reported, slightly higher for the Ovsynch when compared to the Progesterone protocol: 1.91 vs 1.70, respectively. Finally, when considering the number of progressive synchronization treatments implemented over time as covariate, neither Ovsynch nor Progesterone treatment significantly affected pregnancy rates following the first of the six synchronization sessions. However, repeating the synchronization procedure, the progesterone based protocol resulted in significantly higher probability of success in terms of established pregnancies during the second and third re-synchronization sessions.

Meibomian Gland Features and Conjunctival Goblet Cell Density in Glaucomatous Patients Controlled With Prostaglandin/Timolol Fixed Combinations: A Case Control, Cross-sectional Study.

PURPOSE: To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs). MATERIALS AND METHODS: In this cross-sectional study, 60 white patients were treated with PTFCs, 15 with latanoprost+timolol (L+T) unfixed combination, and 15 controls were enrolled. Patients underwent the Ocular Surface Disease Index questionnaire, tear film breakup time, corneal staining, Schirmer test I, and IVCM of MGs and goblet cells. The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD. RESULTS: PTFCs were: latanoprost/timolol (LTFC, 15 eyes), travoprost/timolol (TTFC, 15), bimatoprost/timolol (BTFC, 15), and preservative-free bimatoprost/timolol (PF-BTFC, 15) fixed combinations. Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD, and MMAA (P<0.001), and greater InI and InAW (P<0.05) in glaucoma patients compared with controls. L+T showed worse values compared with PTFCs and PF-BTFC (P<0.05). Preserved PTFCs showed lower MMAD, MMAA, GCD, and greater InI and InAW compared with PF-BTFC (P<0.05) and controls (P<0.001). Differences were not found among PTFCs. InI and InAW significantly correlated with Ocular Surface Disease Index and breakup time (P<0.001), corneal staining (P<0.05), and GCD (P<0.001); GCD correlated with MMAD (P<0.05). CONCLUSIONS: PTFCs were less toxic towards MGs and goblet cells compared with the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

The Role of Nitric Oxide in the Intraocular Pressure Lowering Efficacy of Latanoprostene Bunod: Review of Nonclinical Studies.

Latanoprostene bunod (LBN) is a topical ophthalmic therapeutic for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (OHT). LBN is composed of latanoprost acid (LA) linked to a nitric oxide (NO)-donating moiety and is the first NO-releasing prostaglandin analog to be submitted for marketing authorization in the United States. The role of latanoprost in increasing uveoscleral outflow of aqueous humor (AqH) is well established. Herein, we review findings from nonclinical studies, which evaluated the role of NO in the IOP-lowering efficacy of LBN. Pharmacokinetic studies in rabbits and corneal homogenates indicate that LBN is rapidly metabolized to LA and butanediol mononitrate (BDMN). NO is subsequently released by BDMN as shown by increased cyclic guanosine monophosphate (cGMP) levels in (1) the AqH and iris-ciliary body after administration of LBN in rabbits and in (2) human trabecular meshwork (TM) cells after incubation with LBN. LBN reduced myosin light chain phosphorylation, induced cytoskeletal rearrangement, and decreased resistance to current flow to a greater extent than latanoprost in TM cells, indicating that NO released from LBN elicited TM cell relaxation. LBN also lowered IOP to a greater extent than latanoprost in FP receptor knockout mice, rabbits with transient OHT, glaucomatous dogs, and primates with OHT. Along with results from a Phase 2 clinical study in which treatment with LBN 0.024% resulted in greater IOP-lowering efficacy than latanoprost 0.005%, these data indicate that LBN has a dual mechanism of action, increasing AqH outflow through both the uveoscleral (using LA) and TM/Schlemm's canal (using NO) pathways.

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.

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.

Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy.

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, ß-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

Long interval prostaglandin as an alternative to progesterone-eCG based protocols for timed AI in sheep.

To compare the reproductive performance after TAI in ewes synchronized with mid (12 or 13) or long (14-16 d) interval prostaglandin (PG) or progesterone plus eCG (P4-eCG) based protocols, 440 multiparous Corriedale ewes were synchronized with two PG injections administered 12-16 d apart (PG12, PG13, PG14, PG15 and PG16 respectively), or P4-eCG (MAP sponges 14 d and eCG). Cervical TAI (Day 0) was performed with fresh semen. It was evaluated the ovulated ewes (OE, %) and the ovulation rate (OR) on Day 8 by trans-rectal ultrasonography, the rate of non-return to service between Days 13 and 21 by painted rams, and the pregnancy rate, prolificacy and fecundity on Day 60 by trans-abdominal ultrasonography. No significant differences were found in OE among groups (P>0.05), but P4-eCG achieved higher OR (P<0.05) compared to PG protocols, without differences among them (P>0.05). Similar NRR-21, pregnancy and fecundity were observed among PG15 (64.3, 62.9 and 84.3), PG16 (59.7, 59.7 and 77.8) and P4-eCG (70.3, 66.2 and 95.9), but higher compared to PG12 (42.5, 39.7 and 52.1) and PG13 group (44.0, 40.0 and 48.0, respectively; P<0.05). PG14 achieved intermediate results compared to other groups. No differences were found in prolificacy among groups (P>0.05), except PG13 that was lower compared to P4-eCG (P<0.05). In conclusion, long interval between PG injections (15 or 16 d) determined better reproductive outcome that mid interval (12 or 13 d), equating the P4-eCG based protocol after cervical TAI with fresh semen during the breeding season in sheep.

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.

The physical properties of generic latanoprost ophthalmic solutions are not identical.

PURPOSE: To compare various characteristics of Xalatan® and five generic latanoprost ophthalmic solutions. METHODS: Drop size, volume, pH values, buffer capacity, viscosity, hardness of bottles and costs were determined. Drop sizes were measured in triplicates by micropipettes, and the number of drops counted in three separate bottles of each generic product was determined. pH values were measured in triplicates by a calibrated pH meter. Buffer capacity was exploited by titrating known quantities of strong base into 2.5 ml of each brand and interpolated to neutral pH. Kinematic viscosity was determined by linear regression of timed gravity flow from a vertical syringe through a 21-G cannula. The hardness of the bottles was evaluated by gradually increasing tension on a hook placed around each bottle until a drop was expelled reading the tension on an attached spring scale. RESULTS: Drop sizes and the number of drops in the bottles varied significantly between the generic drugs. The control value of pH in the brand version (Xalatan® ) was markedly lower compared to the generic latanoprost products. Titration of Xalatan® to neutrality required substantially more NaOH compared to the generic latanoprost products. Finally, the viscosity revealed a significant variability between brands. Remarkable differences were found in bottle shapes, bottle hardness and costs of the latanoprost generics. CONCLUSION: Generic latanoprost eye drops should not be considered identical to the original brand version as regards to drop size, volumes, pH values, buffer capacity, viscosity, hardness of bottles and costs. It is likely that these issues affect compliance and intraocular pressure (IOP)-lowering effect. Therefore, re-evaluation of the requirements for introducing generic eye drops seems reasonable.

Assessment of the Anterior Chamber Flare and Macular Thickness in Patients Treated with Topical Antiglaucomatous Drugs.

PURPOSE: To determine the changes in the anterior chamber flare and central macular thickness (CMT) under topical antiglaucomatous therapy. METHODS: This study included 121 eyes of 73 patients and 36 eyes of 18 controls. Glaucoma patients were divided into 3 groups (timolol maleate, latanoprost, and bimatoprost). Control eyes did not receive any medications. Flare and CMT measurements were performed at baseline and follow-up visits (15th day, and 1st, 3rd, 6th, and 12th month). RESULTS: Statistically significant increases were detected in the flare values in the bimatoprost and latanoprost groups (P < 0.001, P = 0.011, respectively). Significant increases were also found in CMT values measured in these 2 groups (P < 0.001, P = 0.002, respectively). However, increased flare and CMT values were not clinically manifested as uveitis and macular edema. Flare and CMT values did not change statistically in the timolol maleate and control groups. CONCLUSIONS: Although the use of prostaglandin (PG) analogs was found to be associated with increased flare and CMT, these increases were not clinically significant. PG analog monotherapy may be safely and effectively used in the treatment of glaucoma.

Time of ovulation and pregnancy outcomes obtained with the prostaglandin-based protocol Synchrovine for FTAI in sheep.

The objective of the present study was to determine the ovarian response induced with the prostaglandin-based protocol Synchrovine (two doses of PGF2α given 7 d apart), as well as the fertility after FTAI. In Experiment 1, 15 females received the Synchrovine protocol using two different PGF2α analogues (Delprostenate vs. D-Cloprostenol). No differences in estrus response, time of ovulation and follicular dynamics were found between both groups (P < 0.05). The ovulation after Synchrovine was synchronized in a similar mean interval (68.8 ± 7.1 h) than when the females received a single dose of PGF2α (70.2 ± 20.7 h; P=NS), but the dispersion between the first and the last ovulation was reduced with this protocol (range 60-84 h vs. 24-96 h, respectively; P < 0.05). In experiment 2, 318 ewes were treated with the Synchrovine protocol and cervical FTAI was performed using different sperm cell concentrations. Pregnancy rate was higher using 200 × 106 and 100 × 106 sperm cells (38.2%, 39/102; and 34.9%, 38/109, respectively) than using 50 × 106 (23.4%, 25/107, P < 0.05). In Experiment 3, 444 ewes received the Synchrovine protocol and were assigned to receive 300 IU of eCG or not at the moment of the second dose of PGF2α, and cervical FTAI was performed 42 h or 48 h after the second dose of PGF2α. No effect was found related to the eCG administration nor the time of insemination. In Experiment 4, 342 received cervical or intrauterine insemination after treatment with the Synchrovine protocol, resulting in greater pregnancy rate for intrauterine insemination than cervical insemination (52.5%, 90/171 vs. 31%, 53/171, P < 0.05). These experiments demonstrate that the Synchrovine protocol effectively induces luteolysis, estrus and ovulation in most of the treated females, and ovulation is synchronized into a narrow window of 24 h. Pregnancy rate obtained with cervical FTAI is around 30-45%, with similar results using 100 × 106 or 200 × 106 sperm cells, the eCG administration seems not to be necessary, the type of PGF2α analogue does not appear relevant, and fertility is improved with intrauterine semen deposition.

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.