In vivo release and retinal toxicity of cyclosporine-loaded intravitreal device.

PURPOSE: To determine the in vivo release profile and retinal safety of cyclosporine A (CsA) delivered from a biodegradable poly-lactide-co-glycolide (PLGA) device in the vitreous cavity of rabbits' eyes. METHODS: A total of 60 animals (60 eyes) divided into two groups were used. For the in vivo release study, 32 eyes received PLGA implants containing 350 µg of CsA, and 16 eyes received the implants without drug (control). Four animals of CsA group and two of the control group were killed weekly until 8 weeks; the vitreous was removed, and CsA concentration was evaluated. Ophthalmological examination was performed in the animals prior to implant placement and weekly during the study period. Electroretinography (ERG) was performed in other six animals for each group, treated and control, at the beginning and at the end of the study (8 weeks) when they were killed and had their eyes processed for histology. RESULTS: No sign of inflammation was noticed on slit lamp examinations and the IOP maintained stable during the study period in CsA and control groups. CsA concentration in the vitreous (ng/ml) was 257.07 ± 117.23, 271.15 ± 98.96, 296.66 ± 86.25, 256.27 ± 99.22, 304.50 ± 88.18, 326.35 ± 105.24, 491.25 ± 119.90 and 589.93 ± 132.55 after 1, 2, 3, 4, 5, 6, 7 and 8 weeks of implantation, respectively. At the end of the study, 21.67 % of mass loss was found. The retina did not show any histological alteration in either group, but a significant reduction in dark-adapted b-wave amplitude was observed in the CsA group, with no changes in a-wave amplitude. CONCLUSIONS: These data show that the PLGA system is safe, but the selective reduction in ERG b-wave amplitude indicates that the PLGA with 350 µg CsA causes retinal function impairment, specifically on the rod postreceptor pathway, 8 weeks after implantation. These ERG changes were not associated with any histological damage as seen at the light microscopy level.

Retinal detachment surgery with silicone oil injection in transconjunctival sutureless 23-gauge vitrectomy.

PURPOSE: To report a surgical technique for retinal detachment surgery using transconjunctival sutureless 23-gauge vitrectomy with silicone oil injection. METHODS: Thirty-one patients with retinal detachment underwent vitreoretinal surgery using a transconjunctival sutureless 23-gauge vitrectomy system. At the end of the procedure silicone oil was injected into all eyes through a microcannula. After removing the microcannula, a bipolar cautery was used in the conjunctiva over the wound to prevent silicone oil reflux. RESULTS: In all patients retinal reattachment and injection of silicone oil through transconjunctival sutureless 23-gauge vitrectomy system was possible. Retinal re-detachment occurred in 8 patients (25.80%) who were submitted to a new vitreoretinal surgery by the technique described above, however, more extensive retinotomy was necessary in all cases, specially inferiorly. Three patients (9.67%) presented silicone oil leakage in subconjuntival compartment. Another surgical procedure was necessary to remove the subconjuntival silicone oil. CONCLUSIONS: The retinal detachment surgery with silicone oil injection in transconjunctival sutureless 23-gauge vitrectomy is a safe and efficient technique to repair retinal detachment and it has the advantage of being minimally invasive.

Pars plana vitrectomy and silicone oil tamponade for acute endophthalmitis treatment.

PURPOSE: To evaluate the outcomes of pars plana vitrectomy and silicone oil injection for the treatment of infectious endophthalmitis. METHODS: 35 cases of endophthalmitis secondary to phacoemulsification (20 patients), trabeculectomy (8 patients), perforating trauma (2 patients), trauma (2 patients), corneal transplantation (1 patient), vitrectomy (1 patient) and corneal ulceration (1 patient) were retrospectively studied. Patients were separated into two groups: Group 1 (n=24): intravitreal antibiotic injection, associated with topical and oral antibiotics; Group 2 (n=11): vitrectomy with intravitreal antibiotic injection and silicone oil injection. The follow-up ranged from 1 to 48 months (mean of 16 months). RESULTS: From 24 patients in group 1, 11 patients (45.83%), had infection controlled with intravitreal antibiotic injection only; 13 patients (54.15%) regressed to uncontrolled endophthalmitis, in which two patients (8.33%) were submitted to evisceration and one patient (4.16%) had corneal melting. The remaining 10 patients (41.66%) with uncontrolled endophthalmitis were submitted to pars plana vitrectomy and silicone oil injection. Six patients (25%) from Group I had retinal detachment during the first month of follow-up and also required pars plana vitrectomy and silicone oil injection. In Group 2 patients (n=11), all of them had controlled infection at the first procedure. In one case (9.09%), a severe proliferative vitreoretinopathy induced loss of vision. CONCLUSION: These results suggest that silicone oil tamponade might be beneficial in the treatment strategy of infectious endophthalmitis.

Implants as drug delivery devices for the treatment of eye diseases / Implantes como dispositivos de distribuição de medicamentos para o tratamento de doenças oculares

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.

O tratamento de doenças do segmento posterior do olho é limitado pela dificuldade no transporte de doses efetivas de fármacos para o vítreo, retina e coróide. Os fármacos aplicados topicamente são pouco absorvidos por causa da baixa permeabilidade dos tecidos oculares externos e ao lacrimejamento. Embora a administração sistêmica seja capaz de transportar fármacos para o segmento posterior do olho, as barreiras hemato-aquosa e hematorretiniana dificultam a absorção e, normalmente, são necessárias doses elevadas, as quais estão geralmente associadas a potenciais efeitos adversos. Injeções intravitreais são capazes de transportar fármacos para o segmento posterior do olho, mas é uma técnica invasiva, pouco tolerada pelos pacientes e apresenta riscos de infecções oculares e danos aos tecidos. Visando a obtenção de níveis terapêuticos adequados de fármacos no segmento posterior do bulbo do olho por longos períodos, sistemas de liberação poliméricos implantados diretamente no vítreo estão sendo investigados para o tratamento de várias doenças vítreo-retinianas. Esses implantes podem ser preparados a partir de diferentes polímeros biocompatíveis, biodegradáveis ou não-biodegradáveis. Nesta revisão, as principais características destes implantes transportadores de fármacos são descritas, expondo suas potencialidades de aplicação clínica.

Pars plana vitrectomy and silicone oil tamponade for acute endophthalmitis treatment / Vitrectomia pars plana e tamponamento por óleo de silicone para o tratamento de endoftalmite aguda

PURPOSE: To evaluate the outcomes of pars plana vitrectomy and silicone oil injection for the treatment of infectious endophthalmitis. METHODS: 35 cases of endophthalmitis secondary to phacoemulsification (20 patients), trabeculectomy (8 patients), perforating trauma (2 patients), trauma (2 patients), corneal transplantation (1 patient), vitrectomy (1 patient) and corneal ulceration (1 patient) were retrospectively studied. Patients were separated into two groups: Group 1 (n=24): intravitreal antibiotic injection, associated with topical and oral antibiotics; Group 2 (n=11): vitrectomy with intravitreal antibiotic injection and silicone oil injection. The follow-up ranged from 1 to 48 months (mean of 16 months). RESULTS: From 24 patients in group 1, 11 patients (45.83 percent), had infection controlled with intravitreal antibiotic injection only; 13 patients (54.15 percent) regressed to uncontrolled endophthalmitis, in which two patients (8.33 percent) were submitted to evisceration and one patient (4.16 percent) had corneal melting. The remaining 10 patients (41.66 percent) with uncontrolled endophthalmitis were submitted to pars plana vitrectomy and silicone oil injection. Six patients (25 percent) from Group I had retinal detachment during the first month of follow-up and also required pars plana vitrectomy and silicone oil injection. In Group 2 patients (n=11), all of them had controlled infection at the first procedure. In one case (9.09 percent), a severe proliferatative vitreoretinopathy induced loss of vision. CONCLUSION: These results suggest that silicone oil tamponade might be beneficial in the treatment strategy of infectious endophthalmitis.

OBJETIVO: Avaliar os resultados da vitrectomia pars plana com tamponamento com óleo de silicone no tratamento de endoftalmite aguda. MÉTODOS: Trinta e cinco pacientes com endoftalmite, sendo 20 secundário à facoemulsificação, 8 por trabeculectomia, 2 por trauma perfurante, 2 por trauma, 1 por transplante de córnea, 1 por vitrectomia, e 1 por úlcera de córnea, foram estudados retrospectivamente. Os pacientes foram separados em dois grupos. Grupo 1 (n=24): injeção de antibiótico intravítreo (AIV), associado com antibióticos oral e sistêmico; Grupo 2 (n=11): vitrectomia com AIV e óleo de silicone. O seguimento variou de 1 a 48 meses (média de 16 meses). RESULTADOS: Dos 24 pacientes no Grupo 1, 11 (45,83 por cento) tiveram controle da infecção apenas com injeção AIV, 13 (54,15 por cento) não controlaram a endoftalmite, sendo que, dois destes (8,33 por cento) foram submetidos à evisceração e um (4,16 por cento) evoluiu para "melting" corneano. Os outros 10 (41,66 por cento) pacientes foram submetidos à vitrectomia pars plana e óleo de silicone. Seis pacientes (25 por cento) do Grupo 1 tiveram descolamento de retina e também necessitaram de vitrectomia pars plana e óleo de silicone. No Grupo 2 (n=11), todos tiveram controle da infecção no primeiro procedimento e não necessitaram de mais intervenções, exceto pela remoção do óleo de silicone três meses depois. CONCLUSÃO:Os resultados sugerem que o tamponamento por óleo de silicone parece ser benéfico na estratégia de tratamento da endoftalmite infecciosa aguda.

Retinal detachment surgery with silicone oil injection in transconjunctival sutureless 23-gauge vitrectomy

PURPOSE: To report a surgical technique for retinal detachment surgery using transconjunctival sutureless 23-gauge vitrectomy with silicone oil injection. METHODS: Thirty-one patients with retinal detachment underwent vitreoretinal surgery using a transconjunctival sutureless 23-gauge vitrectomy system. At the end of the procedure silicone oil was injected into all eyes through a microcannula. After removing the microcannula, a bipolar cautery was used in the conjunctiva over the wound to prevent silicone oil reflux. RESULTS: In all patients retinal reattachment and injection of silicone oil through transconjunctival sutureless 23-gauge vitrectomy system was possible. Retinal re-detachment occurred in 8 patients (25.80 percent) who were submitted to a new vitreoretinal surgery by the technique described above, however, more extensive retinotomy was necessary in all cases, specially inferiorly. Three patients (9.67 percent) presented silicone oil leakage in subconjuntival compartment. Another surgical procedure was necessary to remove the subconjuntival silicone oil. CONCLUSIONS: The retinal detachment surgery with silicone oil injection in transconjunctival sutureless 23-gauge vitrectomy is a safe and efficient technique to repair retinal detachment and it has the advantage of being minimally invasive.

OBJETIVOS: Relatar técnica cirúrgica para descolamento de retina utilizando sistema de 23-gauge com injeção de óleo de silicone. MÉTODOS: Trinta e um pacientes com descolamento da retina foram submetidos a cirurgia vitreorretiniana usando o sistema 23-gauge de vitrectomia transconjuntival sem sutura. Ao final do procedimento o óleo de silicone foi injetado em todos os olhos através de uma microcânula. Após a retirada da microcânula, foi utilizado cautério bipolar na incisão conjuntival para prevenir o vazamento do óleo de silicone. RESULTADOS: Em todos os pacientes foi possível reaplicar a retina e injetar o óleo de silicone através do sistema 23-gauge de vitrectomia transconjuntival. Redescolamento da retina ocorreu em 8 pacientes (25,80 por cento) os quais foram submetidos a uma nova cirurgia vitreorretiniana com a mesma técnica, entretanto, uma retinotomia mais extensa foi necessária em todos estes casos especialmente na parte inferior que foi mais comprometido. Em 3 casos (9,67 por cento) houve extravasamento do óleo de silicone para o compartimento subconjuntival. Novo procedimento foi necessário para remover o silicone subconjuntival. CONCLUSÕES: A cirurgia do descolamento da retina com injeção de óleo de silicone utilizando o sistema 23-gauge de vitrectomia transconjuntival é uma técnica segura e eficiente para o reparo do descolamento da retina e oferece a vantagem de ser um sistema minimamente invasivo.