ABSTRACT
PURPOSE: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique. METHODS: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo. RESULTS: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye. CONCLUSIONS: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies. TRANSLATIONAL RELEVANCE: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.
Subject(s)
Drug Delivery Systems , Animals , Rabbits , Choroid , Optic Nerve/drug effects , Evoked Potentials, Visual/drug effects , Optic Disk , Intravitreal Injections , Needles , CarbonABSTRACT
Antecedentes y objetivo: El espacio supracoroideo (SCS) es una estructura teórica que se sitúa entre el borde interno de la esclera y el límite externo del coroides. El SCS está siendo estudiado por sus posibles usos como vía para la administración de medicamentos y por técnicas quirúrgicas innovadoras para el tratamiento de muchas enfermedades retinianas. La retinitis pigmentosa (RP) es un grupo de trastornos hereditarios y progresivos caracterizados por el detrimento gradual de fotorreceptores que conduce a una discapacidad visual que se manifiesta típicamente como hemeralopía y pérdida progresiva del campo visual. El objetivo del estudio fue definir la morfología de los márgenes coroideos externos mediante el uso de tomografía de coherencia óptica de barrido (SS-OCT) en la RP.Materiales y métodosEstudio observacional retrospectivo diseñado para evaluar la presencia del ESC en la RP. Realizamos SS-OCT en un grupo de 55 pacientes afectados por RP (26 hombres y 29 mujeres, 110 ojos) con una edad media de 51,8±13,7 años. En el grupo de control incluimos a 28 sujetos sanos (6 hombres y 22 mujeres, 56 ojos) con una edad media de 48,8±16,6 años.ResultadosLas imágenes OCT permitieron delinear de manera precisa el margen coroideo externo y el margen escleral interno en los 110 ojos. En el grupo RP se detectó el ESC en 47 de los 110 ojos (42,7%), en el grupo de control se detectó el ESC en 11 ojos (19,6%).Los sujetos del grupo RP con SCS visibles presentaron un menor grosor retiniano (168,4 micrones) en comparación con aquellos con SCS visibles (211,2 micrones, p=0,007). (AU)
Background and objective: The suprachoroidal space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases. Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss. The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP.Material and methodThis is a retrospective observational study designed to evaluate the presence of SCS in RP. We performed swept source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8±13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48.8±16.6 years.ResultsOCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42.7%), in the control group SCS was detected in 11 eyes (19.6%).Subjects with SCS visible (RP group) had reduced retinal thickness (168.4μm) compared to those with not visible SCS (211.2μm, p=0.007). (AU)
Subject(s)
Humans , Choroid/anatomy & histology , Choroid/diagnostic imaging , Retina , Retinal Diseases , Retinitis Pigmentosa/diagnostic imaging , Retrospective Studies , Vision DisordersABSTRACT
The suprachoroidal space is a potential space between the sclera and choroid. Suprachoroidal spacedrug delivery is becoming an applicable method to the ocular posterior segment diseases. Because it targets the choroid, retinal pigment epithelium and retina with high bioavailability and safety, while maintaining low levels elsewhere in the eye. In recent years, new discoveries has been carried out in different areas of interest, such as drug delivery methods, pharmacokinetics and clinical trials. Clinical trials with suprachoroidal space injection of triamcinolone acetonide are executed with promising findings for patients with noninfectious uveitis and diabetic macular edema. Suprachoroidal space triamcinolone acetonide injectable suspension is the first and currently the only agent specifically approved for uveitic macular edema by Food and Drug Administration. Nowadays, many clinical trails with suprachoroidal space drug delivery have been explored, although there are still many risks and uncertainties. With the development of technology in the future, suprachoroidal space drug delivery appears to be a promising treatment modality for ocular posterior segment diseases.
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@#Macular hole retinal detachment(MHRD)mainly occurs in high myopic eyes with posterior scleral staphyloma and always causes severe visual impairment. The pathogenesis of MHRD in high myopic eyes is still unclear. It is generally believed that it involves various complex traction. A variety of surgical methods have been tried to remove retina tractionin order to achieve retina reattachment and macular hole closure. This article reviews the current surgical methods and progress of MHRD in high myopic eyes.
ABSTRACT
The suprachoroidal space (SCS) is the potential space between the sclera and choroid.Drugs delivered through SCS can bypass the sclera,avoiding clearance by conjunctival and scleral blood vessels and lymphatic circulation,so that more drugs can reach the disease tissues such as choroid and retina.SCS drug delivery does not disrupt the ocular integrity,is safer than the intravitreal drug injection and more effective than trans-scleral drug delivery.In addition,SCS delivery only needs a very small volume of drug,which makes it possible to be carried out in multiple parts of the sclera,and the specific disease area can be more precisely targeted.SCS drug delivery is suitable for the treatment of choroidal and retinal diseases.However,currently SCS drug delivery is still a novel field and many aspects need to be more in-depth studied,including its safety,delivery methods,drug formulation and effectiveness.
ABSTRACT
BackgroundAnterior proliferative vitreoretinopathy (aPVR)is a tissue injury and repair progress,and treatment of aPVR is very important in clinic.Chitosan drug delivery system is becoming a hot spot for its large lading dose and long acting duration.ObjectiveThe present study was to investigate the curative effect of a triamcinolone acetonide (TA) drug delivery system after implantation into the suprachoroidal space to treat traumatic aPVR.MethodsaPVR models were created in the left eyes of 65 healthy pigment rabbits by performinga 5 mm penetrating incision 2.5 mm posterior to limbum at 10:30-11:30.The animals were randomly divided into 4groups.Blank chitosan was implanted into the suprachoroidal space as the blank control group.Chitosan with 1 mg TA was implanted in the TA + chitosa group.The TA solution ( containing 1 mg TA) was intravitreally injected in the TA injection group.Fifteen models were used as the traumatic control group.Another 15 left eyes of normal pigment rabbits were used as the normal control group.The thickness of the ciliary tissue was measured using a ultrasound biomicroscope(UBM) 3,5 and 8 weeks after operation.The animals were sacrificed by excessive anesthesia and eyeballswereobtainedforhistopathologicalandultrastructuralexaminations.ResultsHistopathological examination showed the edema of the ciliary tissue and inflammatory cells infiltration in the blank control group,TA injection group and model control group,but mild response was seen in the TA + chitosa group.Severe damage in the ciliary tissue and subcellular organelle was found in the blank and model control groups,but mild damage was detected in the TA + chitosa group under the transmission electron microscope.UBM examination revealed that obvious abnormalities were visible in the ciliary and iris tissue in the blank control group,TA injection group and traumatic control group,but a mild abnormality was seen in the TA + chitosa group.Significant differences in ciliary thickness were exhibited among the 5 groups 2,5 and 8 weeks after operation (F =212.938,515.323,447.919,P＜0.01 ).Compared with the normal control group,ciliary thickness significantly increased in the blank control group and normal control group at various time points (all P＜0.05 ),but that in the TA + chitosa group was significantly lower than the normal control group at various time points ( two weeks:0.484±0.075 vs.0.327 ±0.094 ; five weeks:0.422 ±0.089vs.0.327±0.094 ;eight weeks:0.418±0.085 vs.0.327±0.094) (all P＞0.05). ConclusionsThe chitosan drug delivery system with TA suppresses the excessive proliferation of injured ocular tissue after implantation into the suprachoroidal space,which prevents the formation and development of aPVR.