Abstract Aim: The aim of this study is to report the tolerability, safety and efficacy of a topical triamcinolone acetonide-loaded liposomes formulation (TA-LF) to prevent clinically significant macular edema (CSME) after femtosecond laser-assisted cataract surgery (FLACS). Methods: Fifty-five eyes of 32 patients who underwent FLACS were enrolled. Twenty-seven eyes were assigned to the TA group whereas twenty-eight eyes were assigned to the TA-LF group. In the TA group, eyes were exposed to a conventional topical formulation of triamcinolone acetonide 0.1% for 21 days postoperatively, whereas patients in the TA-LF group received a liposomal formulation containing 2 mg/ml of TA (0.2%). A follow-up consisting on slit-lamp examination, visual acuity, contrast sensitivity, central foveal thickness (CFT) and total macular volume (TMV) (both measured by retinal optical coherence tomography) was performed. Study visits were scheduled at 1 day, 6, and 12 weeks after surgery. Results: The incidence of CSME in the TA group at 6 weeks was 22.2%, in contrast, the incidence of these finding in the TA-LF group was 0%. A conventional steroid formulation (TA 0.1%) was associated with an increased risk of CSME (OR, 9.44; 95% CI, 1.76 - 50.66; p = 0.027). Finally, no ocular or systemic adverse events were reported in any group. Conclusion: TA-loaded liposomal formulation is effective for the prevention of CSME associated with FLACS, and it seems that its therapeutic activity could be superior to the activity of a conventional topical steroid formulation.

Resumen Objetivo: El objetivo de este estudio es informar la tolerabilidad, la seguridad y la eficacia de una nueva formulación de liposomas de uso tópico cargados con acetónido de triamcinolona (FL-AT), útil en la prevención del edema macular clínicamente significativo (EMCS) que ocurre después de la cirugía de catarata asistida con láser de femtosegundo (FLACS). Métodos: Se estudiaron 55 ojos de 32 pacientes a los que se realizó FLACS. Se asignaron 27 ojos al grupo de acetónido de triamcinolona (AT), mientras que 28 ojos fueron asignados al grupo de FL-AT. En el grupo de AT, los ojos se expusieron a una formulación tópica convencional de AT al 0.1% durante 21 días tras la cirugía, mientras que los pacientes en el grupo FL-AT recibieron una formulación liposomal que contenía 2 mg/ml de AT (0.2%). Se realizó un seguimiento clínico que comprendió: examen con lámpara de hendidura, agudeza visual, sensibilidad al contraste, grosor foveal central y volumen macular total. Las visitas del estudio se programaron los días 1 y 6 y al final de la semana 12 del periodo postoperatorio. Resultados: La incidencia de EMCS en el grupo de AT a las 6 semanas fue del 22.2%, en contraste con el grupo de FL-AT, en el cual fue de 0%. La formulación de esteroides convencionales (AT al 0.1%) se asoció con un mayor riesgo de EMCS (OR: 9.44; IC del 95%: 1.76-50.66; p = 0.027). Finalmente, no se reportaron eventos adversos oculares ni sistémicos en ningún grupo. Conclusión: La FL-AT es eficaz para la prevención del EMCS asociado con FLACS, y parece que su actividad terapéutica es superior a la actividad de la formulación de esteroides tópicos convencionales.

Abstract Purpose: Retinal pigment epithelial cells exhibit a propensity for apoptosis in Stargardt macular dystrophy (STGD). Previously, single-nucleotide polymorphisms (SNPs) in the toll-like receptor 4 (TLR4) gene have been related to apoptosis and inflammatory response. Therefore, this study was undertaken to investigate whether TLR4 SNPs are associated with STGD in a family-based study. Methods: Four blood-related Mexican patients with a clinical diagnosis of STGD (4 women) and 12 of their unaffected relatives were included in the study. A total of 109 subjects (40 men and 69 women; age, 63.28 ± 7.93 years) without macular affections, family history, or inherited macular dystrophies were used as controls. SNPs rs4986790, rs1927911, rs12377632, rs2149356, and rs11536889 of the TLR4 gene were genotyped using a Taqman® Allelic Discrimination Assay. Results: The frequency of the minor allele of rs4986790 (G) was significantly higher in STGD patients compared to control subjects (25% vs. 1%, p = 0.0012). The genotype carrying the minor allele of rs4986790 (AG) was more frequent in STGD patients (50%) compared with their relatives and unrelated control subjects (8 and 2.75%, respectively), with statistical significance (p = 0.0048).The allele and genotype frequencies of the remaining SNPs were not significant between STGD patients and control subjects (p > 0.5). Unaffected relatives of STGD patients showed allele and genotype frequencies similar to those observed in control subjects. Conclusion: Minor alleles of the SNPs rs4986790 (G) and genotypes carrying it (AG) were related to clinical STGD in one family. Interestingly, rs4986790 has been described as a promoter of apoptosis. Therefore, this TLR4 gene polymorphism should be considered as a marker in future studies.

Resumen Objetivo: Las células del epitelio pigmentario retiniano tienden a la apoptosis en la distrofia macular de Stargardt (STGD). Anteriormente, los polimorfismos de un solo nucleótido (SNP) del gen del receptor Toll de tipo 4 (TLR4) se habían relacionado con la apoptosis y la inflamación. Por tanto, este estudio se realizó para investigar si los SNP del TLR4 están asociados con la STGD en un estudio familiar. Métodos: Se incluyeron 4 pacientes mexicanos consanguíneos con diagnóstico clínico de STGD (4 mujeres) y 12 familiares no afectados. Se utilizaron como control 109 sujetos (40 hombres y 69 mujeres; edad, 63.28 ± 7.93 años) sin enfermedades maculares ni antecedentes familiares. Los SNP rs4986790, rs1927911, rs12377632, rs2149356 y rs11536889 del gen TLR4 fueron genotipados usando un ensayo de discriminación alélica Taqman®. Resultados: La frecuencia del alelo menor rs4986790 (G) fue significativamente mayor en pacientes con STGD en comparación con los controles (25 vs. 1%; p = 0.0012). El genotipo portador del alelo menor rs4986790 (AG) fue más frecuente en los pacientes con STGD (50%) en comparación con sus familiares y controles (8 y 2.75%, respectivamente) de manera significativa (p = 0.0048). Las frecuencias alélicas y genotípicas de los SNP restantes no fueron significativas entre pacientes con STGD y controles (p > 0.5). Los familiares no afectados mostraron frecuencias alélicas y genotípicas similares a las encontradas en los controles. Conclusión: El alelo menor del SNP rs4986790 (G) y el genotipo portador (AG) se relacionaron con la enfermedad de Stargardt clínica. Curiosamente, el rs4986790 se ha descrito como un promotor de la apoptosis. Así, pues, este polimorfismo del gen TLR4 debe considerarse como un marcador en estudios futuros.

Introdução: Os aminoglicosídeos são potencialmente ototóxicos, sendo que a monitorização tradicional detecta ototoxicidade quando a lesão já aconteceu. Objetivo: Estudamos prospectivamente a audição de pacientes que recebiam amicacina, usando audiometria tonal liminar (ATL) e emissões otoacústicas, produtos de distorção (EOA-PD), visando a suspeita precoce de ototoxicidade e sua prevenção. Forma de estudo: Prospectivo randomizado. Material e método: Avaliamos, com ATL, 29 pacientes em tratamento com amicacina, para detectar alterações audiométricas. Desses 29 pacientes, três tiveram alteração na ATL em 6 e/ou 8 kHz (10,34 %) - um com alteração bilateral; os outros dois, unilateral (quatro ouvidos), todos assintomáticos. Realizamos EOA-PD, para estudar a função coclear. Dos 29 pacientes (58 ouvidos), nove (18 ouvidos) foram afastados do estudo por não completarem as testagens das EOA-PD, ficando 20 pacientes (40 ouvidos) para análise. Resultados: Não encontramos alterações significativas nas respostas das EOA-PD durante o vale e o pico sérico da amicacina, como esperado. Quando comparados os ouvidos com e sem alterações audiométricas, as variações das respostas não foram significativas em 1, 2 e 4 kHz; no entanto, em 6 e 8 kHz mostraram diferenças significativas (p<0,05). As respostas das EOA-PD nos ouvidos com ATL normal apresentaram incrementos mais do que quedas; e o contrário aconteceu nos ouvidos que apresentaram ATL alterada, ou seja: houve mais quedas do que incrementos. Conclusões: a ototoxicidade pode ser monitorada eficazmente com EOA-PD durante a administração da droga, independentemente do horário da sua administração; os incrementos nas respostas poderiam ser um sinal precoce de ototoxicidade por aminoglicosídeos.

Introduction: Aminoglycosides can lead to ototoxicity, but the traditional auditory monitoring detects ototoxicity just when the injury has already occurred. Aim: A prospectively study of the auditory function of patients in treatment with amicacyn using pure tone audiometry (TA) and distortion product otoacoustic emissions (DPOAE) to detect an early suspicion of ototoxicity and its prevention. Study design: Prospective randomized. Material and method: Twenty-nine patients treated with amicacyn were evaluated with TA to detect audiometric changes. Out of 29 patients, three had audiometric changes in 6 and/or 8 kHz (10.34%), one had bilateral and two had unilateral alteration (four ears). They were all asymptomatic. We performed DPOAE to study the cochlear function. Out of 29 patients (58 ears), nine (18 ears) were excluded because they did not have all DPOAE tests, remaining 20 patients (40 ears) to analyze. Results: No specific tendency was found in the DPOAE records during the serum trough and peak of the drug. In a comparative study of ears with and without audiometric changes, no significant difference was found in the response in 1, 2 and 4 kHz; however, a significant difference was observed in 6 and 8 kHz (p<0.05). We found that DPOAE responses of normal ears presented a larger number of increments than decreases when compared to the others. Conclusions: Ototoxicity can be effectively monitored with DPOAE during drug administration, regardless of time of administration, and 6 and 8 kHz are more sensitive frequencies to realize effective auditory monitoring; the increments in responses can be an early sign of ototoxicity by aminoglycosides.