Heterocromia de íris: uma revisão das condições que podem afetar a pigmentação iridiana / Heterochromia: a review of conditions that may affect iris pigmentation

RESUMO A íris é responsável pela cor dos olhos. Ela ainda realiza o controle da quantidade de luz que penetra no olho pela pupila. Variações nos genes de cada indivíduo, além da quantidade e da qualidade de melanina na íris, determinam a cor dos olhos. A heterocromia é caracterizada por diferenças na coloração da íris de um mesmo indivíduo, sendo, na maioria das vezes, benigna. Existem basicamente três tipos de heterocromia de íris: central, setorial e completa. A heterocromia de íris pode ter como causa alterações genéticas e congênitas, relacionadas ou não a síndromes específicas, como a de Sturge-Weber, a de Waardenburg, a de Parry-Romberg e a de Horner congênita. Há também causas adquiridas, como doenças ou lesões, trauma ocular e corpos estranhos intraoculares, uso de certas medicações tópicas, siderose ocular, irites ou uveítes como a síndrome uveítica de Fuchs, dentre outras. Diante de um paciente com heterocromia de íris, deve-se entender o contexto e o curso clínico desse sinal, pois pode se tratar de uma alteração de pigmentação benigna ou existir uma doença base em curso, que requer terapêutica específica. Este artigo de revisão de literatura visa abordar as principais etiologias relacionadas à heterocromia de íris, além de discorrer sobre a anatomia e a fisiologia da coloração iridiana e sobre a fisiopatologia de suas possíveis alterações.

ABSTRACT The iris is responsible for eye color and controls the amount of light that enters the eye through the pupil. Variation in each individual's genes, besides the quantity and quality of melanin in the iris, determine eye color. Heterochromia is characterized by different colors of irises in the same individual, and it is benign in most cases. There are basically three types of heterochromia: central, partial and complete. Heterochromia can be caused by genetic and congenital alterations, which may or may not be related to specific conditions, such as Sturge-Weber syndrome, Waardenburg syndrome, Parry-Romberg syndrome and congenital Horner syndrome. It may be associated to acquired causes like diseases or injuries, such as eye trauma and intraocular foreign bodies, use of some topical medications, ocular siderosis, iritis or uveitis, such as Fuchs´ uveitis, among others. When assessing a patient with heterochromia, one must understand the context and clinical course of this signal, since it may be a benign pigmentation disorder or there may be an underlying disease, which requires specific therapy. This literature review article was set out to address the main etiologies related to heterochromia, in addition to describing the anatomy and physiology of the iris color and the pathophysiology of possible alterations.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma.

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

Evaluation of palpebral fissure and orbital volume after bimatoprost 0.03% orbital injections. Experimental study in rats / Avaliação da fenda palpebral e do volume orbitário após aplicações orbitárias de bimatoprost 0.03%. Estudo experimental em ratos

Objective: To evaluate in experimental animals the changes of the palpebral fissure and the orbital volume after orbital injection of bimatoprost 0.03%. Methods: Two main groups of Wistar rats were analyzed, one after orbital injection of bimatoprost 0.03% and another, a control group, after orbital injection of saline solution. The calculation of the palpebral fissure was done on images by means of computer processing, using the program Image J. After taking photographs, the animals were submitted to bilateral orbital exenteration and the volume was calculated in all the animals by the water displacement method (Archimedes’ Principle). Results: While comparing the measurements of the palpebral fissure and the orbital volume among animals given an injection with bimatoprost 0.03% and the control group it was found that there were no statistically significant differences. Conclusions: In this study there were no statistically significant differences in the measurement of the vertical palpebral fissure and the orbital volume among animals given the orbital injection of bimatoprost 0.03% and the animals of the control group. .

Objetivo: Avaliar em modelos experimentais as alterações da fenda palpebral e do volume orbitário após aplicação orbitária de bimatoprost 0,03%. Métodos: Dois principais grupos compostos por ratos Wistar foram analisados, sendo comparados os animais submetidos à injeção orbitária de bimatoprost 0.03% com os submetidos à injeção orbitária de solução salina. O cálculo da fenda palpebral vertical foi obtido através de imagem computadorizada utilizando-se o programa Image J. Após serem fotografados os animais foram submetidos à exenteração bilateral e o volume orbitário foi calculado pelo método de deslocamento da coluna de água (Princípio de Archimedes). Resultados: Quando foram comparadas as medidas da fenda palpebral vertical e do volume orbitário entre os animais submetidos a injeção de bimatoprost 0.03% e o grupo controle não foi obsevada diferença estatisticamente significante. Conclusão: Neste estudo não houve diferença estatisticamente significante nas medidas da fenda palpebral vertical e no volume orbitário entre os animais submetidos à injeção orbitária de bimatoprost 0.03% e o grupo controle. .

Hyperemia reduction after administration of a fixed combination of bimatoprost and timolol maleate to patients on prostaglandin or prostamide monotherapy.

OBJECTIVE: The aim of this study was to evaluate the change in hyperemia and intraocular pressure (IOP) in patients who switch from prostaglandin or prostamide to a fixed combination of prostamide and timolol maleate. DESIGN: A multicenter, longitudinal, noncontrolled, nonrandomized open trial was conducted. PARTICIPANTS: One hundred forty-four patients (282 eyes) were selected: 60 (41.6%) were on travaprost, 51 (35.4%) on bimatoprost, and 33 (22.9%) on latanoprost. All patients included were unable to attain adequate IOP control with monotherapy and had no contraindications to ß-blockers. INTERVENTION: Patients were treated with a fixed combination of bimatoprost and timolol maleate. Hyperemia was evaluated using a referential table, and IOP was measured at 8:00, 12:00, and 16:00 h both before and after 4 months of treatment. MAIN OUTCOME: IOP and hyperemia were compared at 2 time points: pretreatment and after 4 months. The mean of the 3 IOP measurements taken at various points during the day was considered for analysis. Generalized estimating equations were used for repeated measures and intereye dependency adjustments. RESULTS: Hyperemia and IOP were reduced in all 3 groups, with the same pattern for both eyes. The bimatoprost group had the highest levels of hyperemia before treatment when compared with the latanoprost as well as the travaprost group and had the greatest reduction in hyperemia after treatment (P < 0.01). Regarding IOP, all 3 groups had a significant reduction (P < 0.001), but the bimatoprost group had a lower pretreatment IOP when compared with the travaprost and latanoprost groups. CONCLUSION: A significant reduction in hyperemia was found after switching from monotherapy with prostaglandins or prostamide to a fixed combination of prostamide and a ß-blocker. IOP reduction was significant after the intervention in all 3 groups.

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases.

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation.

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases / Edema macular cistóide bilateral e simultâneo associado com o uso de latanoprost: relato de dois casos

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation.

O edema macular cistóide é um efeito colateral incomum, porém bem conhecido, do latanoprost. São descritos dois casos de edema macular cistóide bilateral e simultâneo associado ao uso de latanoprost, em que foi observada completa resolução do edema após a suspensão da droga.

Immunohistochemical expression of HLA-DR in the conjunctiva of patients under topical prostaglandin analogs treatment.

PURPOSE: Subclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. SUBJECTS AND METHODS: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. RESULTS: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). CONCLUSIONS: The use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

Herpetic keratitis in a patient who used two different prostaglandin analogue ophthalmic solutions: a case report.

PURPOSE: To report a patient with glaucoma who developed recurrent herpetic keratitis while using two different prostaglandin analogue ophthalmic solutions. RESULTS: A 72 year-old male patient with primary open angle glaucoma and a history of herpetic keratitis in the left eye experienced recurrent herpetic keratitis in the left eye after treatment with latanoprost ophthalmic solution. Herpetic flares were controlled after discontinuation of latanoprost. Adding travoprost ophthalmic solution 0.004% to his glaucoma therapy was also associated with a recurrence of herpetic keratitis. CONCLUSION: To our knowledge, this is the first case in which travoprost has been associated to recurrent herpetic keratitis. Further, this is the first report in which a patient has a recurrence of herpetic keratitis associated to two different prostaglandin analogues. These findings suggest that patients with recurrent herpetic keratitis associated to a prostaglandin analogue might be predisposed to a flare-up with other prostaglandin analogues.

[Influence of topical latanoprost on foveal thickness in eyes that underwent uneventful cataract surgery]. / Efeitos da latanoprosta sobre a espessura foveal em olhos submetidos à cirurgia de catarata.

PURPOSE: To study prospectively using optical coherence tomography whether topical latanoprost induces retinal disorders in patients that underwent cataract surgery. METHODS: Randomized, masked-observer, one-month clinical trial. Pseudophakic patients were treated with latanoprost (n=10) or lubricant drop q.d. (control group) (n=10). Half of the patients of each group presented ruptured posterior capsule (Nd:YAG laser). We evaluated the blood-retinal barrier status assessed by optical coherence tomography measurement of retinal thickness in the fovea. Before the beginning of the study and after 15 and 30 days of treatment, optical coherence tomography images were taken, and the visual acuity examination was performed. RESULTS: There was no statistically significant increase in mean foveal thickness when patients instilled placebo (P>0.0610). A statistically significant increase in retinal thickness in the fovea was observed when patients instilled latanoprost (P<0.0004). No changes were observed in visual acuity in both groups. Mean retinal thickness in the fovea was significantly higher in the latanoprost group (P<0.0007). The mean foveal thickness in latanoprost treated eyes with ruptured posterior capsule was statistically greater when compared with that of intact posterior capsule (P<0.0461). When comparing only the patients with that of intact posterior capsule, there was a statistically significant difference in foveal thickness between patients treated with latanoprost (236.4 +/- 29.4 mm) and placebo (197.8 +/- 19.3 mm) only at 30 days of treatment. CONCLUSIONS: Latanoprost may lead to disruption of the blood-retinal barrier in pseudophakic patients, and is more probable to occur in patients with ruptured posterior capsule.

Efeitos da latanoprosta sobre a espessura foveal em olhos submetidos à cirurgia de catarata / Influence of topical latanoprost on foveal thickness in eyes that underwent uneventful cataract surgery

OBJETIVO: Avaliar prospectivamente com o uso da tomografia de coerência óptica se o uso tópico de latanoprosta induz alterações retinianas em pacientes submetidos à cirurgia de catarata. MÉTODOS: Estudo clínico randomizado, com observador mascarado e um mês de duração. Pacientes pseudofácicos foram tratados com latanoprosta (n=10) ou lubrificante ocular uma vez ao dia (grupo controle - placebo) (n=10). Metade dos pacientes de cada grupo possuía capsulotomia posterior (Nd:YAG laser). Avaliamos o status da barreira hemato-retiniana pela medida da espessura retiniana na fóvea com a tomografia de coerência óptica. Exames de tomografia de coerência óptica e medida da acuidade visual foram realizados antes do início do estudo e com 15 e 30 dias de tratamento. RESULTADOS: Não foi observada alteração significante na média da espessura foveal do grupo controle (p>0,0610). Houve aumento significante na média da espessura foveal nos pacientes tratados com latanoprosta (p<0,0004). Não foi observada alteração na acuidade visual em nenhum paciente. A média da espessura retiniana na fóvea foi significativamente maior no grupo da latanoprosta (p<0,0007). A espessura foveal nos olhos tratados com latanoprosta com cápsula posterior rota foi significativamente maior que a dos pacientes com cápsula íntegra (p<0,0461). Comparando apenas os pacientes com cápsula posterior íntegra, houve diferença significante da espessura foveal entre os pacientes tratados com latanoprosta (236,4 ± 29,4 mm) e placebo (197,8 ± 19,3 mm) apenas na avaliação realizada com 30 dias de tratamento. CONCLUSÕES: Latanoprosta pode levar à quebra da barreira hemato-retiniana em pacientes pseudofácicos. Isso é mais provável de ocorrer em pacientes com cápsula posterior rota.

PURPOSE: To study prospectively using optical coherence tomography whether topical latanoprost induces retinal disorders in patients that underwent cataract surgery. METHODS: Randomized, masked-observer, one-month clinical trial. Pseudophakic patients were treated with latanoprost (n=10) or lubricant drop q.d. (control group) (n=10). Half of the patients of each group presented ruptured posterior capsule (Nd:YAG laser). We evaluated the blood-retinal barrier status assessed by optical coherence tomography measurement of retinal thickness in the fovea. Before the beginning of the study and after 15 and 30 days of treatment, optical coherence tomography images were taken, and the visual acuity examination was performed. RESULTS: There was no statistically significant increase in mean foveal thickness when patients instilled placebo (P>0.0610). A statistically significant increase in retinal thickness in the fovea was observed when patients instilled latanoprost (P<0.0004). No changes were observed in visual acuity in both groups. Mean retinal thickness in the fovea was significantly higher in the latanoprost group (P<0.0007). The mean foveal thickness in latanoprost treated eyes with ruptured posterior capsule was statistically greater when compared with that of intact posterior capsule (P<0.0461). When comparing only the patients with that of intact posterior capsule, there was a statistically significant difference in foveal thickness between patients treated with latanoprost (236.4 ± 29.4 mm) and placebo (197.8 ± 19.3 mm) only at 30 days of treatment. CONCLUSIONS: Latanoprost may lead to disruption of the blood-retinal barrier in pseudophakic patients, and is more probable to occur in patients with ruptured posterior capsule.

The effects of prostaglandin analogues on the blood aqueous barrier and corneal thickness of phakic patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: To evaluate the effects of topical latanoprost, travoprost, and bimatoprost on the blood-aqueous barrier and central corneal thickness (CCT) of patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). DESIGN: Prospective, randomized, masked-observer, crossover clinical trial. METHODS: A total of 34 phakic patients with POAG or OHT with no previous history of intraocular surgery or uveitis completed the study. Patients were randomized to use latanoprost 0.005%, travoprost 0.004%, or bimatoprost 0.03% once daily (2000 hours) for 1 month, followed by a washout period of 4 weeks between each drug. Aqueous flare was measured with a laser flare metre. CCT was calculated as the average of five measurements using ultrasound pachymetry. All measurements were performed by a masked observer (1000 h). RESULTS: There were no statistically significant differences between baseline mean IOP, mean CCT, and mean flare values among the groups. There was no statistically significant increase in mean flare values from baseline in all groups (P>0.05). There were no statistically significant differences between mean flare values among the groups (P>0.05). All medications significantly reduced the mean IOP from baseline (P<0.0001). IOP reduction obtained with travoprost (7.3+/-3.8 mmHg) was significantly higher than that obtained with latanoprost (4.7+/-4.2 mmHg) (P=0.01). A statistically significant reduction in mean CCT (0.6+/-1.3%) from baseline was observed when patients instilled bimatoprost (P=0.01). CONCLUSIONS: Latanoprost, travoprost, and bimatoprost had no statistically significant effect on the blood-aqueous barrier of phakic patients with POAG or OHT. Bimatoprost may be associated with a clinically irrelevant reduction in mean CCT.

Conjunctival changes induced by prostaglandin analogues and timolol maleate: a histomorphometric study

PURPOSE: To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva. METHODS: Fifty New Zealand rabbits were divided in 5 groups of 10 animals. The left eyes were treated daily with one drop of bimatoprost 0.03 percent, travoprost 0.004 percent, latanoprost 0.005 percent, timolol maleate 0.5 percent or artificial tears containing benzalkonium chloride (BAK) for 30 days. The right eyes served as controls. Superior limbic conjunctival biopsies were performed at the 8th and 30th day in 5 rabbits of each group. The conjunctiva was fixed with 10 percent formaldehyde, followed by HE and PAS staining. Morphohistometric quantitative analyses were performed to evaluate the following parameters: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. RESULTS: At the 8th and 30th posttreatment days, all groups, except one that received artificial tears, exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin (PG) analogues groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (p=0.0035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (p=0.0006), and at the 30th day in those treated with bimatoprost (p=0.0021) and latanoprost (p=0.009). CONCLUSIONS: Although a moderate, diffuse inflammatory infiltrate was observed in PG-treated eyes, no changes in conjunctival epithelial thickness or subconjunctival collagen density were observed with these medications, suggesting that these drugs induce fewer changes than timolol maleate in the rabbit conjunctiva.

OBJETIVOS: Comparar alterações histológicas induzidas por medicação anti-glaucomatosa na conjuntiva de coelhos. MÉTODOS: Cinqüenta coelhos da raça Nova Zelândia foram divididos em 5 grupos de 10 animais. Os olhos esquerdos foram tratados com uma gota diária de bimatoprosta 0,03 por cento, travoprosta 0,004 por cento, latanoprosta 0,005 por cento, maleato de timolol 0,5 por cento ou lágrimas artificiais contendo cloreto de benzalcônio (BAK) por 30 dias. Os olhos direitos serviram como controles. Foram realizadas biópsias conjuntivais límbicas superiores no 8º e 30º dias em 5 coelhos de cada grupo. A conjuntiva foi fixada com formaldeído 10 por cento, seguido por coloração de HE e PAS. Foi realizada análise quantitativa morfohistométrica para avaliar os seguintes parâmetros: infiltrado inflamatório, espessura epitelial, número de células caliciformes, diâmetro e número de vasos sanguíneos. RESULTADOS: No 8º e 30º dias de tratamento, todos os grupos, exceto aquele que recebeu lágrimas artificiais, exibiram infiltrado inflamatório difuso, composto por linfócitos e neutrófilos, sendo mais denso no grupo timolol do que nos grupos dos análogos de prostaglandinas. No 30º dia, o grupo timolol apresentou um aumento na densidade de colágeno subepitelial e um aumento significativo da espessura epitelial (p=0,0035). A densidade de células caliciformes aumentou significativamente no 8º dia no grupo tratado com travoprosta (p=0,0006), e no 30º dia nos grupos tratados com bimatoprosta (p=0,0021) e latanoprosta (p=0,009). CONCLUSÕES: Embora tenha sido observado um infiltrado inflamatório difuso e moderado nos olhos tratados com análogos de prostaglandinas, não houve alterações na espessura epitelial conjuntival ou densidade colágena subepitelial com essas medicações, sugerindo que essas drogas induzem menores alterações que o maleato de timolol na conjuntiva de coelhos.

A 6-week, multicenter, randomized, double-masked, parallel-group study comparing travoprost 0.004% to latanoprost 0.005% followed by 6-week, open-label treatment with travoprost 0.004%.

OBJECTIVE: The aim of this study was to compare the tolerability and efficacy of once-daily travoprost 0.004% versus latanoprost 0.005% for 6 weeks followed by 6 weeks of once-daily travoprost 0.004% in decreasing intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). METHODS: This multicenter, randomized, doublemasked, active-controlled, parallel-group trial was conducted at 32 centers across Latin America. Patients aged > or =18 years with OAG or OH were randomly assigned to receive topical travoprost 0.004% or latanoprost 0.005% 1 drop QD (9 PM) for 6 weeks (masked phase). At 6 weeks, all patients were assigned to receive open-label travoprost 0.004% 1 drop QD (9 PM) for 6 additional weeks (open-label phase). Study visits were scheduled at weeks 1, 2, 4, 6, 8, and 12. At each study visit, IOP was measured at 5 PM (+/-1 hour; approximately 20 hours after study drug administration). IOP changes from baseline were combined (pooled) from the 1-, 2-, 4-, and 6-week data to provide a comparison between the 2 treatment groups. Ocular adverse events (AEs) were monitored using slit-lamp examination. RESULTS: A total of 302 patients were enrolled (travoprost group, 155 patients; latanoprost group, 147 patients). The mean (SD) age of the travoprost group was 61.9 (10.6) years; 60.6% were female; and 47.1% were white. The mean (SD) age of the latanoprost group was 60.5 (12.4) years; 62.6% were female; and 49.0% were white. Mean IOP values were not significantly different between the travoprost and latanoprost groups at baseline (24.7 vs 24.2 mm Hg) or 6 weeks; however, the between-group difference in reductions from baseline in pooled IOP during the masked phase of the study was statistically significant (-8.3 vs -7.5 mm Hg; P = 0.009). At weeks 6 and 12, mean lOP levels were 16.1 and 16.2 mm Hg, respectively, in the travoprost group and 16.4 and 16.1 mm Hg in the group that was switched from latanoprost to travoprost (all, P = NS). The most common ocular AEs that occurred with masked travoprost, latanoprost, and open-label travoprost were hyperemia (26.9%, 12.2%, and 5.3%, respectively), discomfort (3.2%, 3.4%, and 1.1%), and pruritus (4.5%, 2.0%, and 2.1%). CONCLUSIONS: In this population of patients with OAG or OH, 6-week treatment with travoprost 0.004% was associated with a significantly greater decrease from baseline in pooled IOP compared with latanoprost 0.005% 20 hours after administration. There were no significant differences between the 2 groups. Travoprost and latanoprost were well tolerated.

Comparison of the stability, efficacy, and adverse effect profile of the innovator 0.005% latanoprost ophthalmic solution and a novel cyclodextrin-containing formulation.

Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradation at higher temperatures, whereas the cyclodextrin-containing formulation was stable at temperatures up to 40 degrees C. Formulations were assayed in a randomized double-blind clinical study in patients with primary open-angle glaucoma and/or ocular hypertension. Both latanoprost ophthalmic solutions produced comparable reduction of intraocular pressure. Conjunctival hyperemia was observed in 11.9% and 11.3% of the patients treated with the innovator and the cyclodextrin-containing formulations, respectively. There were no significant differences between the 2 ophthalmic solutions in efficacy or in the measured adverse effect. It is concluded that these 2 latanoprost ophthalmic solutions yield comparable efficacy and adverse effect outcomes. The cyclodextrin-containing formulation, however, has an improved stability.

Conjunctival changes induced by prostaglandin analogues and timolol maleate: a histomorphometric study.

PURPOSE: To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva. METHODS: Fifty New Zealand rabbits were divided in 5 groups of 10 animals. The left eyes were treated daily with one drop of bimatoprost 0.03%, travoprost 0.004%, latanoprost 0.005%, timolol maleate 0.5% or artificial tears containing benzalkonium chloride (BAK) for 30 days. The right eyes served as controls. Superior limbic conjunctival biopsies were performed at the 8th and 30th day in 5 rabbits of each group. The conjunctiva was fixed with 10% formaldehyde, followed by HE and PAS staining. Morphohistometric quantitative analyses were performed to evaluate the following parameters: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. RESULTS: At the 8th and 30th posttreatment days, all groups, except one that received artificial tears, exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin (PG) analogues groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (p=0.0035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (p=0.0006), and at the 30th day in those treated with bimatoprost (p=0.0021) and latanoprost (p=0.009). CONCLUSIONS: Although a moderate, diffuse inflammatory infiltrate was observed in PG-treated eyes, no changes in conjunctival epithelial thickness or subconjunctival collagen density were observed with these medications, suggesting that these drugs induce fewer changes than timolol maleate in the rabbit conjunctiva.

Blood-aqueous barrier changes after the use of prostaglandin analogues in patients with pseudophakia and aphakia: a 6-month randomized trial.

OBJECTIVES: To investigate the effects of prostaglandin analogues on the blood-aqueous barrier and to evaluate the occurrence of cystoid macular edema in aphakic or pseudophakic patients with glaucoma. METHODS: In this randomized, masked-observer, 6-month clinical trial, patients with primary open-angle, pseudophakic, or aphakic glaucoma were treated once daily with bimatoprost (n = 16), latanoprost (n = 15), or travoprost (n = 17) or twice daily with unoprostone (n = 16) or lubricant drops (control group) (n = 16). Blood-aqueous barrier status, which was assessed using a laser flare meter; intraocular pressure; the occurrence of angiographic cystoid macular edema; and conjunctival hyperemia were evaluated. RESULTS: Mean flare values were significantly higher in the bimatoprost, latanoprost, and travoprost groups throughout follow-up (P < .02). Four latanoprost-treated eyes, 1 bimatoprost-treated eye, and 1 travoprost-treated eye developed cystoid macular edema; all cases resolved after discontinuation of the prostaglandin analogue and treatment with topical diclofenac sodium. Mean intraocular pressure reductions after 6 months were higher for the latanoprost (26%), bimatoprost (28%), and travoprost (29%) groups than for the control (3%) and unoprostone (14%) groups (P< .05). Bimatoprost induced significantly higher hyperemia scores than latanoprost, unoprostone, and placebo (P< .01). CONCLUSION: Bimatoprost, latanoprost, and travoprost use may lead to disruption of the blood-aqueous barrier in patients with pseudophakia and aphakia.

Current status of prostaglandin therapy: latanoprost and unoprostone.

Latanoprost, a prostaglandin F(2alpha) analog prodrug, and unoprostone, an analog of a prostaglandin metabolite, have been shown to be effective in decreasing intraocular pressure when used alone or in combination with other ocular hypotensive agents. The increase in the uveoscleral outflow and some of the side effects are probably FP-receptor mediated, which may account for some differences between the cited drugs. This article reviews the recent literature available on the clinical efficacy of these prostanoids, as well as the studies directly comparing these drugs.

A double-masked, randomized clinical trial comparing latanoprost with unoprostone in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of latanoprost 0.005% once daily with unoprostone 0.12% twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). DESIGN: An 8-week, double-masked, randomized, parallel-group, single-center clinical trial. PARTICIPANTS: A total of 108 patients with POAG or OH were enrolled. INTERVENTIONS: After completing a wash-out of ocular hypotensive medications, patients were randomized to receive either latanoprost once daily in the evening plus placebo once daily in the morning, or unoprostone twice daily (morning and evening). MAIN OUTCOME MEASURES: IOP was measured at 10:00 AM and at 5:00 PM at baseline and at week 8, and before 12:00 noon at week 2. Ocular and systemic safety assessments were performed. RESULTS: From an overall baseline of 24.1 mmHg, latanoprost reduced IOP by 6.7 mmHg (28%) and unoprostone reduced IOP by 3.3 mmHg (14%). The difference between the groups of 3.4 mmHg was significant (P: < 0.001, analysis of covariance; 95% confidence interval [CI]: -4.7 to -2.1) in favor of latanoprost. A >/=30% reduction in mean IOP from baseline was achieved by 44% of latanoprost-treated patients compared with 8% of unoprostone-treated patients. The incidence of adverse events was low and comparable between the groups. CONCLUSIONS: Latanoprost administered once daily was significantly more effective in reducing IOP compared with unoprostone administered twice daily in patients with POAG and OH.