Manifestação ocular incomum em paciente com incontinência pigmentar / Unusual ocular manifestation in a patient with incontinentia pigmenti

RESUMO Incontinência pigmentar, também conhecida como síndrome de Bloch-Sulzberger, é uma doença rara de herança dominante ligada ao X cujas manifestações clínicas incluem lesões dermatológicas típicas combinadas com acometimento neurológico, oftalmológico e dentário. Alterações oculares são comuns e variadas, sendo o acometimento da retina o mais frequente e associado a perda visual severa. Foi relatado um caso de uma criança com perda visual grave decorrente de glaucoma, sem alteração retiniana significativa.

ABSTRACT Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare dominant X-linked inheritance disease whose clinical manifestations include typical dermatological lesions combined with neurological, ophthalmic and dental involvement. Ocular involvment is common and diverse and retinal changes are the most frequent and associated with serious visual loss. We reported a case of a child with severe visual loss due to glaucoma, with no significant retinal changes.

Alteração do tecido conjuntivo orbitário após aplicação de bimatoprost: estudo experimental em ratos / Changes of orbital connective tissue after bimatoprost injection. Experimental study in rats

RESUMO O bimatoprost é utilizado comumente como a droga de primeira escolha no tratamento do glaucoma primário de ângulo aberto. Hiperemia conjuntival, crescimento dos cílios, enoftalmia, escurecimento cutâneo periocular, sulco palpebral profundo e prurido ocular têm sido relatados em pacientes que receberam bimatoprost em doses únicas diárias durante cerca de 3 meses. O mecanismo exato para estes efeitos adversos permanece desconhecido. Objetivo: Verificar em animais de experimentação, as alterações do tecido conjuntivo orbitário após injeção retrobulbar de bimatoprost 0,03%. Métodos Foram utilizados trinta e seis ratos machos (Rattus norvegicus albinus) submetidos a diferentes períodos de injeção retrobulbar de bimatoprost à direita. O material exenterado foi submetido à análise histológica, morfométrica (diâmetro, densidade numérica e densidade de volume dos adipócitos) e imunohistoquímica para marcação do VEGF. Os resultados destas análises foram submetidos à análise descritiva com o auxílio do software R. O nível de significância adotado foi 5%. Para as comparações foi proposto o modelo de regressão linear com efeitos mistos. Resultados: Na amostra estudada, as órbitas submetidas a injeções retrobulbares de bimatoprost apresentaram ao redor do nervo óptico tecido conjuntivo mais espesso, com inúmeros capilares e vasos de vários calibres e a redução da quantidade, diâmetro e volume das células adiposas estatisticamente significativo quando comparado à órbita contralateral e ao grupo controle. Conclusão: Neste estudo observaram-se as seguintes alterações potencialmente reversíveis do tecido conjuntivo orbitário nos ratos submetidos à injeção retrobulbar de bimatoprost: 1) redução da quantidade, do diâmetro e do volume das células adiposas orbitárias; 2) neovascularização local; 3) espessamento e remodelamento das fibras de colágeno na cavidade orbitária.

ABSTRACT Bimatoprost is commonly used as the drug of first choice in the treatment of primary open-angle glaucoma. Conjunctival hyperemia, eyelash growth, enophthalmos, periocular skin pigmentation, deep lid sulcus and itching eyes have been reported in patients that daily received single dosages during a three month period. The exact mechanism for these adverse effects remains unknown. Objective: to verify alterations, in test animals, of the orbital connective tissue after peribulbar injections of bimatoprost 0.03% using histological and immune-histochemical analysis. Methods: thirty six male test rats (Rattus norvegicus albinus) were subjected to various periods of periocular injections of bimatoprost 0.03% in the right eye.All extracted material was submitted to histological, morphometric (diameter, numeric density and density of adipocyte volume) and immune-histochemical analysis to mark the vascular endothelial growth factor (VEGF). These analysis results were then submitted to a descriptive analysis with the help of R software. The significance level used was 5%. For comparison, the model of linear regression with mixed effects was proposed. Results: In the sample studied, the eye sockets that were continuously submitted to bimatoprost had a denser conjunctival tissue around the optic nerve, with numerous capillaries and blood vessels of various sizes and a reduction of quantity, diameter and volume of adipose cells of statistic importance when compared to the contralateral eye socked and the control group. Conclusion: In this study, the following potentially reversible changes of orbital connective tissue were observed in test rats subjected to periocular injection of bimatoprost: 1) reduction of quantity, diameter and volume of orbital adipose cells; 2) local neovascularization; 3) thickening and remodeling of collagen fibers in the orbital cavity.

Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits / Efeitos dos análogos da prostaglandina na velocidade do fluxo sanguíneo e resistência na artéria oftálmica de coelhos

ABSTRACT Purpose: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. Methods: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. Results: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. Conclusion: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

RESUMO Objetivo: O objetivo deste estudo foi investigar os efeitos dos análogos da prostaglandina (PGAs) no fluxo sanguíneo da artéria oftálmica em coelhos. Métodos: Cinquenta e cinco coelhos da raça Nova Zelândia clinicamente saudáveis foram divididos em seis grupos para tratamento com formulação tópica de diferentes APGs (bimatoprosta BAK, tafluprosta BAK-free, travoprosta BAK, travoprosta POLYQUAD e latanoprosta BAK) e formulações contendo apenas o conservante cloreto de benzalcônio (BAK). Foi realizada ultrassonografia com Doppler antes e após os tratamentos. Os valores do pico da velocidade sistólica (PSV) e da velocidade diastólica final foram obtidos e o índice de resistência (RI) foi então calculado. A análise estatística foi realizada para comparar as diferenças entre cada droga no pré e pós-tratamento, além das diferenças no pós-tratamento entre as drogas. Resultados: Estes colírios PGAs não afetaram o PSV. A bimatoprosta com o conservante BAK, travoprosta com o conservante POLYQUAD e latanoprosta com o conservante BAK não alteraram o RI. Já o tratamento com tafluprosta sem conservante (BAK-free) e travoprosta com o conservante BAK promoveram redução similar dos valores do RI. Não houve diferença significativa na comparação entre valores pré e pós-tratamento quando BAK foi administrado isoladamente. Conclusão: Os PGAs tafluprosta BAK-free e travoprosta BAK melhoraram o fluxo sanguíneo na artéria oftálmica em coelhos da raça Nova Zelândia sugerindo que estes medicamentos possam contribuir na prevenção da progressão do glaucoma.

Enoftalmia causada por uso tópico unilateral de Bimatoprost / Unilateral enophthalmos induced by the unilateral use of topical Bimatoprost

RESUMO O autor descreve o caso de uma paciente que apresenta o olho direito com o sulco palpebral profundo e enoftalmia deste lado, tratado durante uma década com Bimatoprost tópica. Concluem que os achados clínicos são provavelmente efeitos colaterais do medicamento.

ABSTRACT The author describes a case report of a patient with unilateral enophthalmia and deep palpebral sulcus probably induced by the topical use of Bimatoprost on the side of the collateral effects described.

Effect of Bimatoprost on the Permeability of Trabecular Meshwork Cell Monolayer

PURPOSE: To investigate the effects of bimatoprost on the permeability of cultured human trabecular meshwork cells (HTMC) monolayer. METHODS: HTMCs were cultured until confluency in the inner Transwell chamber and then exposed to benzalkonium chloride, brimonidine, latanoprost or bimatoprost for 1 week. Carboxyfluorescein permeability through the HTMC monolayer was measured using a spectrofluorometer after 2 hours in the outer chamber. Cellular viability was assessed using the MTT assay. RESULTS: Each drug diluted at 1/1000X did not affect the cellular survival (p > 0.05). Brimonidine, latanoprost and bimatoprost did not affect the carboxyfluorescein permeability through the HTMC monolayer (p > 0.05). The carboxyfluorescein permeability was not different between latanoptost and bimatoprost after 1 week of exposure (p > 0.05). CONCLUSIONS: Bimatoprost, a drug known to increase trabecular outflow, does not affect the carboxyfluorescein permeability through the HTMC monolayer. Thus, the effect on the trabecular outflow of bimatoprost may not be significant.

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. .

Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.</p><p><b>METHODS</b>In this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.</p><p><b>RESULTS</b>Of the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).</p><p><b>CONCLUSIONS</b>Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.</p>

Comparing the Efficacy of Latanoprost (0.005%), Bimatoprost (0.03%), Travoprost (0.004%), and Timolol (0.5%) in the Treatment of Primary Open Angle Glaucoma

PURPOSE: To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma. METHODS: This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events. RESULTS: The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student's t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements. CONCLUSIONS: Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.

The Effects of Prostaglandin Analogues on the Corneal Thickness

PURPOSE: To evaluate the effects of prostaglandin analogues on the corneal thickness of patients with primary open-angle glaucoma (POAG) or normal tension glaucoma (NTG). METHODS: This study included 130 eyes of 65 patients who were diagnosed with POAG or NTG. All patients were divided into two groups; one group received prostaglandin analogues, while the other group received alternative ocular hypotensive eyedrops. Corneal thickness, best corrected visual acuity, and flare in the anterior chamber were measured and compared before treatment and at least 24 months (mean: 27 months) after treatment. RESULTS: The mean decrease in corneal thickness was statistically significant in the group using prostaglandin analogues, but not in the control group. Among the various prostaglandin analogues used, travoprost and latanoprost decreased mean corneal thickness, but bimatoprost had no effect. Best corrected visual acuity, refraction power, and flare in the anterior chamber did not change significantly in either group of patients when ocular hypotensive eyedrops were used. CONCLUSIONS: Prostaglandin analogues lower intraocular pressure and decrease corneal thickness if used over a 24 months.

Clinical Course of Bimatoprost-induced Periocular Skin Hyperpigmentation after Stopping Bimatoprost Treatment

PURPOSE: To evaluate the demographic and clinical characteristics of bimatoprost-induced periocular skin hyperpigmentation. METHODS: The chart analyses of 16 patients in whom cosmetically noticeable periocular skin hyperpigmentation developed after starting bimatoprost therapy were reviewed. Data collated included age, medication history, dates of starting and stopping bimatoprost treatment, and the subjective assessment of the periocular hyperpigmentation at initial detection as well as follow-up visits. Periocular hyperpigmentation was graded using an arbitrary scale from 0 to 3. The number of days to the onset of hyperpigmentation and to pigment resolution was determined and their associations to demographic and other clinical parameters were analyzed. RESULTS: Patients had variable grades of periocular hyperpigmentation at presentation (mean, 1.53+/-0.66). Bimatoprost-induced periocular hyperpigmentation appeared 1-10 (mean, 4.3+/-2.6) months after initiation of bimatoprost therapy. Resolution of skin hyperpigmentation was noted 2-10(mean 6.8+/-1.9) months after stopping bimatoprost treatment. There was a minor correlation(R=+0.19) between the number of days to resolution of hyperpigmentation and the number of days when bimatoprost was used. At 12 months after stopping bimatoprost treatment, 12 of the 13 patients had complete resolution of periocular hyperpigmentation. However, weak hyperpigmentation remained in one patient. CONCLUSIONS: Bimatoprost-induced hyperpigmentation is benign and reversible.

Two Cases of Deepening of the Upper Lid Sulcus from Topical Bimatoprost Therapy

PURPOSE: To report two cases of deepening of the upper lid sulcus following bimatoprost. METHODS: A 54-year-old woman who used bimatoprost for one week and a 70-year-old woman who used bimatoprost for 4 months developed deep lid sulcus. Both were using bimatoprost for glaucoma treatment. RESULTS: Both patients also showed improvement of dermatochalasis and widening of the palpebral fissure. One week after discontinuing bimatoprost, the lid sulcus of the 54-year-old returned to baseline and exophthalmometry was unchanged. The orbital CT of the 70-year-old was normal. She did not complain about deepening of the lid sulcus, and she has not discontinued treatment due to this adverse effect.

The Short Term Effects of Bimatoprost on Optic Nerve Head and Peripapillary Retinal Blood Flow

PURPOSE: To demonstrate the effects of bimatoprost on the optic nerve head (ONH) and peripapillary retinal blood flow. METHODS: Sixteen healthy volunteers were recruited. In a randomized, double-blind design, one eye received a drop of bimatoprost and the other eye a drop of placebo. ONH and peripapillary retinal blood flow parameters (flow, volume, velocity) were measured with HRF before, and at 1, 6 and 24 hours after eyedrops and blood pressure (BP), heart rate (HR), and intraocular pressure (IOP) were recorded. RESULTS: The 16 subjects comprised 13 males and 3 females with a mean age of 27.3 +/- 2.4 years. IOP decreased significantly in the bimatoprost-treated eyes at 1, 6 and 24 hours after eyedrops (p<0.05). BP and HR were unchanged after bimatoprost eyedrops. The flow was significantly higher in the temporal peripapillary retina in the bimatoprost-treated eyes 1 hour after eyedrops and the velocity was also higher 6 hours after eyedrops at the same location. At the optic disc, there was a significant increase of the volume in the bimatoprost group 1 hour after eyedrops. There was no significant decrease of HRF parameters in the bimatoprost-treated eyes. CONCLUSIONS: These results suggest that bimatoprost does not have any adverse effect on ONH or peripapillary retinal blood flow.