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.

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. .

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.

Immunologic corneal graft rejection after administration of topical latanoprost: a report of two patients

To report endothelial corneal graft rejection after administration of topical latanoprost eye drops. Two eyes of two patients with a history of multiple intraocular procedures prior to penetrating keratoplasty developed endothelial graft rejection one month after administration of topical latanoprost. Cystoid macular edema developed simultaneously in one patient. Latanoprost may trigger endothelial graft rejection in susceptible eyes

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.

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.

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.

Choroidal detachment after topical prostaglandin analogs: case report.

OBJECTIVE: To report three cases of delayed choroidal detachment after treatment with topical prostaglandin analogs. MATERIAL AND METHOD: Intervention three case reports. Four eyes of three patients with chronic angle closure glaucoma developed choroidal detachment after using topical prostaglandin analogs. RESULTS: Three patients with chronic angle closure glaucoma developed chroidal detachment in one week, three weeks and two years after using travoprost, bimatoprost and latanoprost respectively. All of them resolved after discontinuation of these medications. All of the eyes that developed chroidal detachment were pseudophakic. CONCLUSION: Travoprost, bimatoprost and latanoprost may lead to choroidal detachment and hypotony. Pseudophakic patients may be at high risk of the development of chroidal detachment. Topical prostaglandin analogs should be used cautiously in these patients.

Efficacy and safety of latanoprost for glaucoma treatment: a three-month multicentric study in India.

PURPOSE: To evaluate the short-term efficacy and safety of 0.005% topical latanoprost in Indian eyes. DESIGN: Prospective non-randomised open-label multicentric trial. METHODS: One hundred and fifty patients with ocular hypertension (OHT), primary open-angle, pseudoexfoliation or pigmentary glaucoma were enrolled at four centers. Each center contributed at least 20 patients. Following baseline measurements, 0.005% latanoprost was applied topically once daily in the evening for three months. Patients were examined at 2, 6 and 12 weeks. The primary outcome measure was mean intraocular pressure (IOP) reduction. The mean diurnal variation of IOP (difference between highest and lowest IOP) at baseline and at 12-weeks was compared. RESULTS: One hundred and thirty of 150 enrolled patients completed the study. One randomly selected eye of each patient was included for analysis. At three months, latanoprost reduced the mean IOP from 24.9 (+/- 3.16) mmHg at baseline to 16.10 (+/- 2.7) mmHg, a reduction of 35.25%. 83% had a reduction in IOP of > 25%. The IOP reduction was maintained throughout the study period, and was not affected by gender or age of the patient. One eye did not show any response to the drug. Daytime diurnal variation of IOP was reduced from 4.5 to 2.9 mmHg. 20 patients had conjunctival hyperemia. Six patients had side effects requiring withdrawal from the study. CONCLUSIONS: In this short-term multicentric study, latanoprost effectively reduced IOP and stabilised the diurnal curve in Indian eyes. There were no clinically significant ocular or systemic adverse effects.

Comparison between latanoprost and brimonidine efficacy and safety in Indian eyes.

PURPOSE: To compare the short-term efficacy and safety of topical latanoprost and brimonidine in Indian eyes. MATERIALS AND METHODS: Twenty-eight patients with ocular hypertension, primary open-angle, pseudoexfoliation or pigmentary glaucoma were enrolled. Following baseline measurements, latanoprost was applied topically once daily in the evening for 12-weeks. After a washout period, brimonidine was applied twice daily in all patients for 6 weeks; 16 patients continued for 12 weeks. Patients were examined at 2, 6 and 12 weeks. The primary outcome measure was the difference in mean intra ocular pressure (IOP) reduction at 6 and 12 weeks. The mean diurnal variation of IOP at baseline and at 12 weeks was also compared. RESULTS: Twenty-six of 28 enrolled patients completed the study. One randomly selected eye of each patient was used for analysis. At 6 weeks, the mean IOP reduction was 11.2 mm Hg (+/- 2.9 mmHg) with latanoprost and 6 mmHg (+/- 3.3 mmHg) with brimonidine. At 12 weeks this was 10.8 mmHg (+/- 2.8 mmHg) and 6.9 mmHg (+/- 3.1 mmHg) respectively. At 6 weeks 85.7% (24) eyes obtained more than 25% reduction in IOP with latanoprost compared to 13 (46.4%) with brimonidine. IOP reduction was maintained with both drugs throughout the study period. Two eyes did not show any response to brimonidine. Latanoprost reduced the diurnal variation of IOP from 5.10 to 2.90 mmHg; brimonidine reduced it from 4.70 to 3.90 mmHg. Conjunctival hyperaemia was present in one patient on latanoprost and three patients on brimonidine. Two patients experienced drowsiness with brimonidine. Neither drug produced side effects necessitating withdrawal from the study. CONCLUSION: In this short-term study, both latanoprost and brimonidine effectively reduced IOP and stabilised the diurnal curve in Indian eyes. Latanoprost was more effective than brimonidine.