Luteal tissue blood flow and side effects of horse-recommended luteolytic doses of dinoprost and cloprostenol in donkeys.

This study assessed luteolysis and side effects in jennies receiving standard horse-recommended doses of cloprostenol and dinoprost. Sixteen cycles of eight jennies were randomly assigned in a sequential crossover design to receive dinoprost (5 mg, i.m.) and cloprostenol (0.25 mg, i.m.) at 5-d post-ovulation. B-mode and Doppler ultrasonography were employed to assess luteal tissue size and blood flow before (-15 min and 0h) and after (0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, and 48h) administering PGF2α. Immunoreactive progesterone concentrations were assayed at similar timepoints via RIA. Side effects such as sweating, abdominal discomfort, and diarrhea were scored at 15-min-intervals for 1h after PGF2α. Data normality was assessed with the Shapiro-Wilk's test. Luteal tissue size and blood flow were analyzed using PROC-MIXED and post-hoc by Tukey. Non-parametric tests analyzed side effect variables. The luteal blood flow increased overtime by 27% at 45 min and peaked by 49% at 3 h for dinoprost, and conversely, it increased by 14% at 30 min and peaked at 39% at 5h for cloprostenol (P<0.05). Luteal blood flow was reduced by 50%, 25%, and 10% on both groups at 8, 12, and 24h (P<0.05). Immunoreactive progesterone concentrations decreased in 0.5h for dinoprost and 1h for cloprostenol and gradually decreased by 48h (P<0.05). Dinoprost induced greater sudoresis scores, while cloprostenol resulted in greater abdominal discomfort and diarrhea scores (P<0.05). In conclusion, dinoprost and cloprostenol effectively induced luteolysis with distinct side effects; this could guide practitioners' case selection to use one or another PGF2α.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

Bilateral choroidal effusion after selective laser trabeculoplasty. / Desprendimiento coroideo seroso bilateral tras trabeculoplastia selectiva láser.

Selective laser trabeculoplasty (SLT) is an effective treatment to treat open-angle glaucoma with a low risk of complications. The case is presented of a 73 year-old woman with uncontrolled primary open-angle glaucoma who underwent selective laser trabeculoplasty in both eyes and developed bilateral choroidal effusion.

The fixed combination efficacy assessment in patients with secondary neovascular glaucoma and diabetes mellitus.

PURPOSE: To assess IOP-lowering efficacy of bimatoprost/timolol fixed combination (Ganfort®) in patients with diabetes mellitus (DM) and uncontrolled secondary neovascular glaucoma (NG). MATERIALS AND METHODS: Fifty patients (51 eyes) with uncontrolled secondary neovascular glaucoma and diabetes mellitus were enrolled in the study. All patients with an uncontrolled IOP have been proposed to switch current IOP-lowering therapy to Ganfort®. In case target IOP level was not reached filtration surgery was recommended. Ganfort® administration - once a day in the morning. RESULTS: IOP-lowering has been observed in all patients when switched to Ganfort®. Mean IOP level was almost 3-x lower versus baseline in 72.5% of patients (37 eyes). The patients achieved target IOP of 15-17 mmHg. As a result, no surgical intervention was required. Significant IOP-lowering has been observed in another group of patients (14 eyes, 27.5 %) nevertheless due to glaucoma progression, these patients are still subjected to surgical treatment. CONCLUSION: IOP-lowering fixed combination Ganfort® (Allergan) can be used in patients with secondary neovascular glaucoma and diabetes mellitus as a drug of choice to control the IOP level. Even in cases when target IOP is not achieved, Ganfort® can be administered in pre-operative period and helps to reduce postoperative complications.

Prostaglandin analogue-induced pigmentation of the skin of the nasal septum and nasal alae in a glaucoma patient.

PURPOSE: To present a case of topical prostaglandin analogue-induced skin pigmentation in a location previously never reported, with a differential diagnostic significance. CASE REPORT: An 83-year-old man successfully treated for primary open-angle glaucoma of both eyes with the bimatoprost/timolol fixed combination for 6 years reported increased pigmentation of the skin of the nasal septum and alae. According to his report, the darkened skin area was not present when he was a young or middle-aged man. The patient had noted periocular pigmentation and deepening of the upper lid sulcus on both sides, which developed during the years of his bimatoprost/timolol treatment. Dermatology consultation excluded any nevus, malignancy, or other pathology as a cause of the pigmentation. The otorhinolaryngology consultation failed to identify any pathologic condition in the nasal cavity, but described mild chronic senile rhinitis. CONCLUSIONS: The acquired pigmentation of the skin of the nasal septum and alae in our patient represents a new form of cutaneous pigmentation induced by topical prostaglandin analogue therapy, which may have differential diagnostic significance in clinical practice. We speculate that the senile rhinitis of the patient increased the exposure of the nasal skin to the prostaglandin analogue solution drained via the nasolacrimal duct, and could therefore play a role in the development of skin pigmentation in this location.

A retrospective review and observational study of outcomes and safety of bimatoprost ophthalmic solution 0.03% for treating eyelash hypotrichosis.

BACKGROUND: The efficacy and safety of bimatoprost ophthalmic solution 0.03% for treating hypotrichosis were shown in a randomized controlled trial and in an open-label study. To date, no data on real-world experience have been published. OBJECTIVE: To evaluate long-term patient satisfaction, usage patterns, and safety of bimatoprost 0.03% in clinical practice. MATERIALS AND METHODS: In this retrospective chart review with a cross-sectional design, adult patients exposed to bimatoprost 0.03% for at least 12 months were randomly sampled from 16 investigational sites. Charts were reviewed for medication usage characteristics and adverse events (AEs). At a study visit, questionnaires eliciting patient-reported outcomes were administered and spontaneously reported AEs were tabulated. RESULTS: Analysis included 585 subjects with a mean (SD) treatment duration of 19.3 (4.3) months. Patient satisfaction with bimatoprost 0.03% was 92.5%; on average, approximately 3 applications per week maintained benefits. Overall, 27.4% of patients spontaneously recalled experiencing AEs while on treatment; however, patient charts showed that only 4 AEs were documented. No instances of iris hyperpigmentation occurred. No serious or severe AEs were noted. CONCLUSION: Treatment with bimatoprost 0.03% for at least 12 months is safe, and long-term use is associated with a high degree of satisfaction.

[Evaluation of the effectiveness of Ganfort treatment in patients with secondary neovascular glaucoma associated with diabetes mellitus].

PURPOSE: To evaluate the effectiveness of bimatoprost/timolol fixed combination (Ganfort) in decreasing intraocular pressure (IOP) in patients with diabetes mellitus (DM) and uncontrolled secondary neovascular glaucoma (NG). MATERIAL AND METHODS: The study included 50 patients (51 eyes) with diabetes mellitus and sings of uncontrolled secondary NG, which was later confirmed by the results of ophthalmological assessment. All the patients were offered to change their IOP-lowering medications and if the new regimen is still ineffective--to undergo drainage surgery. Therefore they were switched to Ganfort once daily in the morning. RESULTS: After switching the therapy a decrease of intraocular pressure was observed in 100% of cases. In 72.5% of patients (37 eyes) the average IOP was almost 3 times lower than at the baseline and achieved target values (15-17 mm Hg), thus allowing to avoid surgical intervention. In 27.5% of patients (14 eyes), despite a significant decrease of IOP, surgical treatment was considered still necessary due to glaucoma progression and, therefore, drainage surgery was performed. CONCLUSION: The IOP-lowering combination Ganfort (Allergan) can be used in patients with secondary neovascular glaucoma and diabetes mellitus as the treatment of choice. Even if target IOP is not achieved, Ganfort is still useful as a preoperative medication able to reduce postoperative hemorrhagic complications.

Skin graft hypertrichosis associated with prostaglandin analog in the treatment of glaucoma.

Prostaglandin analogs are commonly used in the treatment of glaucoma. They are a safe and effective treatment associated with few side effects. Common local side effects include conjunctival hyperemia, iris pigmentation, and eyelash hypertrichosis. The authors present a case of a patient using travoprost treatment for primary open-angle glaucoma, who underwent excision of a lower eyelid basal cell carcinoma and reconstruction with an upper eyelid tarsoconjunctival flap and overlying skin graft. The patient developed hypertrichosis of the skin graft attributable to prostaglandin analog use.

Safety and efficacy of bimatoprost solution 0.03% topical application in patients with chemotherapy-induced eyelash loss.

Few dermatologic conditions carry as much anxiety and emotional distress as hair loss resulting from a disease condition such as alopecia areata or as a result of cytotoxic drug treatment, e.g., after chemotherapy. Bimatoprost 0.03% solution is a Food and Drug Administration-approved prescription product indicated for the treatment of eyelash hypotrichosis. The product was investigated in a double-masked, randomized, and placebo-controlled study in patients who had significant eyelash loss or hypotrichosis as a result of chemotherapy. Once-daily treatment with bimatoprost ophthalmic solution 0.03% to the upper eyelid margin restored eyelash growth and prominence more quickly than the slower, natural course of recovery observed in the vehicle control subjects. The eyelash prominence measured using a validated Global Eyelash Assessment (GEA) scale demonstrated a statistically significant increase over placebo following 6 months of treatment. Efficacy was also demonstrated using a validated objective digital image analysis methodology to show significant increase in eyelash length, thickness/fullness, and darkness in these patients. Bimatoprost was found to be well tolerated over the 1-year treatment period.

Hemorrhagic choroidal detachment after use of anti-glaucomatous eye drops: case report.

Eighty-two-year-old patient with a pacemaker using warfarin due to arrhythmia and having an intraocular lens in the right eye, developed spontaneous hemorrhagic choroidal detachment one day after the use of combined preparation of 0.5% timolol maleate and 0.004% travoprost, due to primary open-angle glaucoma. Hemorrhagic detachment was detected by anterior and posterior segment examination, as well as B-scan ultrasonography. After the detachment, excessive increased intraocular pressure was controlled with oral carbonic anhydrase inhibitor, cycloplegic and steroid therapy. After four months, visual acuity was 20/20 and the intraocular pressure was under control with 0.5% timolol maleate and 1% brinzolamide. Controlled reduction of the intraocular pressure should be considered, particularly in older patients under anticoagulant therapy and that had undergone prior ocular surgery.

Hemorrhagic choroidal detachment after use of anti-glaucomatous eye drops: case report / Descolamento hemorrágico de coroide após o uso de colírios antiglaucomatosos: relato de caso

Eighty-two-year-old patient with a pacemaker using warfarin due to arrhythmia and having an intraocular lens in the right eye, developed spontaneous hemorrhagic choroidal detachment one day after the use of combined preparation of 0.5% timolol maleate and 0.004% travoprost, due to primary open-angle glaucoma. Hemorrhagic detachment was detected by anterior and posterior segment examination, as well as B-scan ultrasonography. After the detachment, excessive increased intraocular pressure was controlled with oral carbonic anhydrase inhibitor, cycloplegic and steroid therapy. After four months, visual acuity was 20/20 and the intraocular pressure was under control with 0.5% timolol maleate and 1% brinzolamide. Controlled reduction of the intraocular pressure should be considered, particularly in older patients under anticoagulant therapy and that had undergone prior ocular surgery.

Paciente de oitenta e dois anos de idade com marca-passo e utilizando varfarina devido à arritmia cardíaca e com uma lente intraocular no olho direito, desenvolveu descolamento de hemorrágico espontâneo de coroide um dia após o uso de colírio combinado de maleato de timolol a 0,5% e travoprosta a 0,004%, devido ao glaucoma de ângulo aberto primário. O descolamento hemorrágico foi detectado por análise do segmento anterior e posterior, bem como ultrassonografia modo B. Após o descolamento, o aumento excessivo da pressão intraocular foi controlado por inibidor da anidrase carbônica via oral, terapia cicloplégica e esteroides. Após quatro meses, a acuidade visual era 20/20 e a pressão intraocular estava sob controle com o maleato de timolol a 0,5% e brinzolamida a 1%. A redução controlada da pressão intraocular deve ser considerada, especialmente em pacientes idosos sob terapia anticoagulante e que tinham sido submetidos à cirurgia ocular prévia.

Reproductive hormone profiles in sows on estrus synchronization using estradiol dipropionate and prostaglandin F(2α)-analogue and the reproductive performance in female pigs on commercial farms.

Changes in ovarian structures and hormonal profiles in estradiol dipropionate (EDP)-induced pseudopregnant sows following PGF2α-analogue (PGF2α-A) administration and practicality of the estrus synchronization protocol using EDP and PGF2α-A on estrus expression and reproductive performance in commercial conditions were investigated. Pseudopregnancy was defined as absence of estrus maintained for at least 20 days after EDP treatment in this study. When 4 pseudopregnant sows induced by 20 mg EDP were treated with PGF2α-A as 0.175 mg cloprostenol twice at a 24-hr interval between 20 and 28 days after EDP treatment, plasma progesterone concentrations rapidly decreased after treatment. The luteinizing hormone surge and ovulation were detected in all sows. The number of ovulated follicles was 17.3 ± 1.1 (SEM). On commercial farms, 94.2% of 52 gilts and 95.2% of 21 sows received EDP became pseudopregnant. When these pseudopregnant females (48 gilts and 20 sows) were treated with PGF2α-A as described above, estrus was detected in all females at 6.1 ± 0.3 days for gilts and 5.5 ± 0.2 days for sows after the first PGF2α-A treatment. There were no significant differences in farrowing rate (85.0 - 100%), average total litter size (10.0 - 11.4), average born alive litter size (9.4 - 10.3) and average piglet birth weight (1.56 - 1.71 kg) between PGF2α-A treated pseudopregnant female pigs that were inseminated during synchronized estrus and females inseminated during spontaneous estrus. This study indicates that estrus synchronization programs using EDP and PGF2α-A are available as practical and convenient procedures for commercial pig farms.

Topical bimatoprost 0.03% and iatrogenic eyelid and orbital lipodystrophy.

The prostaglandin F2a (PGF2a) analogue bimatoprost 0.03% (Allergan, Inc, Irvine, California) has been employed for the treatment of hypotrichosis since it gained Food and Drug Administration approval as Latisse in 2008. In this report, the authors retrospectively review the cases of 7 patients who presented to their outpatient ophthalmology clinic with glaucoma. These patients had periorbital hollowing due to fat atrophy as a side effect of topical ophthalmic bimatoprost therapy. The series of patients described in this report emphasizes the small but significant risk of periocular fat changes associated with bimatoprost 0.03%, which is the exact formulation marketed as Lumigan for glaucoma treatment. Patients using Latisse for its cosmetic enhancement of eyelash length should be warned of this potentially disfiguring side effect, since the cosmetic and ophthalmic preparations are identical. Such changes can be irreversible, and the implications of the decision to prescribe this drug either in the form of an eyelash application or for topical ophthalmic use should be clearly understood by both clinicians and patients alike.

The effect of additional topical cyclosporine or vitamin A on the ocular surface during antiglaucoma medication administration.

PURPOSE: To investigate the effects of topical application of cyclosporine or vitamin A on the ocular surface during the concurrent administration of antiglaucoma drugs. METHODS: Thirty rabbits were randomized into 5 groups. Group 1 was administered timolol, group 2 received travoprost, group 3 received a travoprost/timolol fixed combination solution, group 4 received timolol and travoprost, and group 5 received timolol, travoprost, and dorzolamide. Each group was divided into a subgroup that received only the antiglaucoma medication (subgroup A), a subgroup that received topical cyclosporine in addition to the antiglaucoma medication (subgroup B), and a subgroup that received topical vitamin A in addition to the antiglaucoma medication (subgroup C). Conjunctival impression cytology specimens were collected at baseline and at weeks 1, 3, and 6. Conjunctival biopsy specimens were collected at week 6. RESULTS: The impression cytologic study results are as follows: statistically significant differences were found between groups 4A and 4B and between groups 4A and 4C at week 6 (p = 0.004, p = 0.006, respectively) and between groups 5A and 5B and between groups 5A and 5C at weeks 3 and 6 (p = 0.006, p = 0.008 at week 3, p = 0.003, p = 0.004 at week 6, respectively). No statistically significant differences were found between subgroup B and subgroup C in any of the groups at any of the times evaluated (p > 0.05). The conjunctival biopsy specimens from groups 1, 2, and 3 showed no distortion, but groups 4A and 5A showed distortion of the conjunctival epithelial structures. Groups 4B, 4C, 5B, and 5C showed less distortion of the conjunctival epithelial structures. CONCLUSION: Administration of cyclosporine or vitamin A may reduce the adverse ocular surface changes caused by long-term administration of antiglaucoma drugs.

Bilateral upper eyelid retraction caused by topical bimatoprost therapy.

The authors report a case with upper eyelid retraction caused by topical bimatoprost therapy. Topical bimatoprost 0.03% was administered to a 69-year-old woman with bilateral normal-tension glaucoma. It was first administered to the left eye, and 3 weeks later, therapy on the right side of the eye was initiated. One week after the initiation of therapy on the right side, right upper eyelid retraction occurred, and 63 days after starting treatment on the left side (42 days after initiation on the right side), conspicuous bilateral upper eyelid retraction was observed. Bimatoprost instillation was then stopped and the medication was switched to latanoprost 0.005%. Upper eyelid retraction was reversed to normal levels approximately 1 week after cessation of bimatoprost therapy. In conclusion, a rare case of upper eyelid retraction caused by topical bimatoprost therapy, which was reversed after discontinuation of the medication, is reported.

[In vitro evaluation for corneal damages by anti-glaucoma combination eye drops using human corneal epithelial cell (HCE-T)].

The combination of anti-glaucoma eye drops is frequently used in clinical treatment, and it is known that the combination can cause corneal damage. Recently, an anti-glaucoma combination eye drops is developed, and the treatment by the combination eye drops is expected to enhance quality of life. However, effects of the combination eye drops on corneal epithelial cell damage have not been clarified. In this study, we investigated the corneal epithelial cell damage of commercially available anti-glaucoma combination eye drops, such as Xalacom® (latanoprost/timolol maleate combination eye drops), Duotrav® (travoprost/timolol maleate combination eye drops) and Cosopt® (dorzolamide hydrochloride/timolol maleate combination eye drops) using the human corneal epithelial cell (HCE-T). The cytotoxicity in Xalacom® was higher than that in Xalatan® (eye drops containing latanoprost) and Timoptol® (eye drops containing timolol maleate), and the benzalkonium chloride (BAC) and timolol maleate were related to cytotoxicity in Xalacom®. The cytotoxicity in Duotrav® and Cosopt® was lower than that in Timoptol®. The Duotrav® is preserved with a non-BAC system (POLYQUAD, polidronium chloride). Therefore, it was suggested that the POLYQUAD related to the low cytotoxicity in Duotrav®. On the other hand, the D-mannitol reduced the cytotoxicity by BAC in this study. This result suggested that the cytotoxicity in Cosopt® was reduced by D-mannitol. The Duotrav® and Cosopt® may be less damaging to the ocular surface of glaucoma patients receiving long-term eye drop therapy in compared with the combination of anti-glaucoma eye drops.

A 12-week, double-masked, parallel-group study of the safety and efficacy of travoprost 0.004% compared with pilocarpine 1% in Chinese patients with primary angle-closure and primary angle-closure glaucoma.

OBJECTIVE: To examine the intraocular pressure-lowering efficacy and safety of travoprost 0.004% and pilocarpine 1% in Chinese patients with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) after laser iridotomy in China. PATIENTS AND METHODS: Thirty patients with PAC or PACG after laser iridotomy were randomized into this double-masked, parallel-group study. Qualified patients had a mean intraocular pressure (IOP) between 21 and 35 mm Hg; inclusive at 9 AM at eligibility visit and previously undergone laser peripheral iridotomy at least 30 days before screening visit. Patients were treated with travoprost 0.004% once daily or pilocarpine 1% 4 times daily for 12 weeks after appropriate washout of glaucoma medications. Efficacy and safety evaluations were conducted at weeks 4, 8, and 12. IOP measurements were performed at 9 AM and 4 PM at baseline and week 12 visits, except at the weeks 4 and 8, when the IOP measurement was undertaken respectively at 9 AM or 4 PM only. The degree and distribution of peripheral anterior synechiae was evaluated by gonioscopy at baseline and week 12, respectively. RESULTS: Both the treatment groups showed statistically significant IOP reductions from baseline, except for the results of pilocarpine group at 4 PM in week 12. Travoprost demonstrated a statistically superior IOP reduction (7.6 mm Hg) compared with pilocarpine (1.9 mm Hg; P=0.04) at 4 PM over the 12-week period. There was no difference in peripheral anterior synechiae degree and distribution in week 12 from baseline for both treatment groups. No serious adverse event was found in both the groups. CONCLUSIONS: Travoprost 0.004% once daily provides effective IOP-lowering efficacy with significantly greater IOP reduction from baseline when compared with pilocarpine 1% 4 times daily at 4 PM over the 12-week period. Travoprost 0.004% once daily is safe and well tolerated in PAC or PACG patients.

Human health hazards of veterinary medications: information for emergency departments.

BACKGROUND: There are over 5000 approved prescription and over-the-counter medications, as well as vaccines, with labeled indications for veterinary patients. Of these, there are several products that have significant human health hazards upon accidental or intentional exposure or ingestion in humans: carfentanil, clenbuterol (Ventipulmin), ketamine, tilmicosin (Micotil), testosterone/estradiol (Component E-H and Synovex H), dinoprost (Lutalyse/Prostamate), and cloprostenol (Estromate/EstroPlan). The hazards range from mild to life-threatening in terms of severity, and include bronchospasm, central nervous system stimulation, induction of miscarriage, and sudden death. OBJECTIVE: To report medication descriptions, human toxicity information, and medical management for the emergent care of patients who may have had exposure to veterinary medications when they present to an emergency department (ED). DISCUSSION: The intended use of this article is to inform and support ED personnel, drug information centers, and poison control centers on veterinary medication hazards. CONCLUSION: There is a need for increased awareness of the potential hazards of veterinary medications within human medicine circles. Timely reporting of veterinary medication hazards and their medical management may help to prepare the human medical community to deal with such exposures or abuses when time is of the essence.