Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Medidas imitanciométricas em crianças com ausência de emissões otoacústicas Acoustic immittance in children without otoacoustic emissions

Partindo da hipótese de que alterações da função de orelha média possam prejudicar a captação das EOAs, é possível que a ausência destas, em lactentes, esteja associada a discretas alterações timpanométricas. OBJETIVO: Verificar a associação entre resposta de EOAT e alteração imitanciométrica com a sonda de 226Hz em lactentes. MÉTODOS: Estudo de coorte contemporânea com corte transversal. Foram avaliados 20 lactentes com ausência de EOAT (grupo pesquisa) e 101 lactentes com presença de EOAT (grupo comparação), com idades variando entre o nascimento e oito meses. Os lactentes foram submetidos a: timpanometria; pesquisa dos limiares de reflexo acústico contralateral com estímulos de 0,5k, 1k, 2k, 4kHz e ruído de faixa larga; emissões otoacústicas (transiente e por produtos de distorção). O potencial evocado auditivo de tronco encefálico para pesquisa do limiar de resposta foi realizado no grupo pesquisa. RESULTADOS: Observou-se diferença estatisticamente significante entre os grupos (p<0,05), caracterizada pela redução na altura timpanométrica e aumento do limiar de reflexo acústico no grupo pesquisa e a ocorrência de discreto comprometimento de orelha média, no grupo pesquisa, associada às respostas eletrofisiológicas normais. CONCLUSÃO: O uso combinado da timpanometria e do reflexo acústico, em lactentes, acrescenta precisão no diagnóstico de alteração de orelha média.<br>Considering the hypothesis that middle ear changes can impair the recording of otoacoustic emissions, it is possible that absent otoacoustic emissions in infants could be associated with a light tympanometric change. AIM: To study the association between transient otoacoustic emissions and changes in acoustic immittance measurements with 226Hz probe tone in neonates. METHODS: Cross-sectional contemporary cohort study. 20 infants with no transient otoacoustic emissions (study group) and 101 infants with transient otoacoustic emissions (control group), with ages ranged from birth to eight months, were assessed. Infants were submitted to: admittance tympanometry; contralateral acoustic reflex threshold with stimulus of 0.5, 1, 2, 4 kHz and broad band noise; transient and distortion product otoacoustic emissions. The auditory brain response was used to study the threshold in neonates without transient otoacoustic emissions. RESULTS: Significant statistical differences were observed between the groups (p < 0.005), characterized by reduction in tympanometric configuration and increase acoustic reflex thresholds in the study group. These data suggest the occurrence of middle ear mild impairment in infants without transient otoacoustic emissions associated with normal auditory brain response. CONCLUSION: tympanometry associated with acoustic reflex adds accuracy to the diagnosis of middle ear abnormalities