PDF(Pubmed)
Abstract：
UNASSIGNED: To determine the effectiveness of aerosol-delivered methotrexate (AD-MTx) in a large-animal (porcine) model of proliferative vitreoretinopathy (PVR).
UNASSIGNED: Prospective, randomized, interventional, double-masked, controlled, large-animal study with predetermined clinical and histopathologic outcome criteria.
UNASSIGNED: Half of the pigs were randomly assigned to receive an identical volume of aerosol-delivered normal saline (AD-NS) using identical delivery systems and treatment intervals.
UNASSIGNED: Proliferative vitreoretinopathy was surgically induced in 16 pigs (8 males and 8 females), randomly assigned to receive 2 doses (group A) or 3 doses (group B) of either AD-MTx (1.6 mg/0.4 ml) or normal saline (AD-NS). Group A pigs were euthanized at week 2 (n = 8), and group B pigs were euthanized at week 3 (n = 8). Masked clinical PVR scores (0-6) by a vitreoretinal surgeon and histopathology PVR scores (0-8) by a masked ophthalmic pathologist were used to determine outcomes.
UNASSIGNED: The mean, combined clinical and histopathology scores (both anterior and posterior) were used to determine the overall treatment effect between the groups.
UNASSIGNED: The mean masked score (± standard deviation) when all grading end points (clinical + histopathology) were combined was a mean of 8.0 ± 2.3 in the AD-MTx group versus a higher 9.9 ± 2.0 in the AD-NS control group (P = 0.05). The clinical score was 3.88 ± 1.2 in the AD-MTx group versus 4.63 ± 1.6 in the AD-NS group (P = 0.16). The histopathology score for anterior PVR was 2.5 ± 0.8 in the AD-MTx group versus 2.5 ± 0.5 in the AD-NS group (P = 0.50), and the posterior PVR was 1.63 ± 1.6 in the AD-MTx group versus 2.75 ± 1.3 in the AD-NS group (P = 0.07). When the frequency of methotrexate dosing in group A (2 doses) was compared with that in group B (3 doses), the mean score was 8.75 versus 9.13 (P = 0.38), respectively, suggesting an insignificant difference.
UNASSIGNED: After surgical induction of PVR in an aggressive, high-risk, large-animal model, AD-MTx reduced posterior PVR formation compared with AD-NS. Additional dosing at week 3 did not improve the outcomes. No difference in anterior PVR formation was noted with intervention. This novel drug delivery system has implications for PVR reduction and warrants further investigation.
UNASSIGNED: Proprietary or commercial disclosure may be found after the references.
UNASSIGNED: Prospective, randomized, interventional, double-masked, controlled, large-animal study with predetermined clinical and histopathologic outcome criteria.
UNASSIGNED: Half of the pigs were randomly assigned to receive an identical volume of aerosol-delivered normal saline (AD-NS) using identical delivery systems and treatment intervals.
UNASSIGNED: Proliferative vitreoretinopathy was surgically induced in 16 pigs (8 males and 8 females), randomly assigned to receive 2 doses (group A) or 3 doses (group B) of either AD-MTx (1.6 mg/0.4 ml) or normal saline (AD-NS). Group A pigs were euthanized at week 2 (n = 8), and group B pigs were euthanized at week 3 (n = 8). Masked clinical PVR scores (0-6) by a vitreoretinal surgeon and histopathology PVR scores (0-8) by a masked ophthalmic pathologist were used to determine outcomes.
UNASSIGNED: The mean, combined clinical and histopathology scores (both anterior and posterior) were used to determine the overall treatment effect between the groups.
UNASSIGNED: The mean masked score (± standard deviation) when all grading end points (clinical + histopathology) were combined was a mean of 8.0 ± 2.3 in the AD-MTx group versus a higher 9.9 ± 2.0 in the AD-NS control group (P = 0.05). The clinical score was 3.88 ± 1.2 in the AD-MTx group versus 4.63 ± 1.6 in the AD-NS group (P = 0.16). The histopathology score for anterior PVR was 2.5 ± 0.8 in the AD-MTx group versus 2.5 ± 0.5 in the AD-NS group (P = 0.50), and the posterior PVR was 1.63 ± 1.6 in the AD-MTx group versus 2.75 ± 1.3 in the AD-NS group (P = 0.07). When the frequency of methotrexate dosing in group A (2 doses) was compared with that in group B (3 doses), the mean score was 8.75 versus 9.13 (P = 0.38), respectively, suggesting an insignificant difference.
UNASSIGNED: After surgical induction of PVR in an aggressive, high-risk, large-animal model, AD-MTx reduced posterior PVR formation compared with AD-NS. Additional dosing at week 3 did not improve the outcomes. No difference in anterior PVR formation was noted with intervention. This novel drug delivery system has implications for PVR reduction and warrants further investigation.
UNASSIGNED: Proprietary or commercial disclosure may be found after the references.
摘要：
■确定气溶胶递送甲氨蝶呤（AD-MTx）在大型动物（猪）增生性玻璃体视网膜病变（PVR）模型中的有效性。
■预期，随机化，介入,双面蒙面,控制,具有预定临床和组织病理学结果标准的大型动物研究。
■一半的猪被随机分配接受相同体积的气溶胶递送生理盐水（AD-NS），使用相同的递送系统和治疗间隔。
■在16只猪（8只雄性和8只雌性）中手术诱发增生性玻璃体视网膜病变，随机分配接受2剂（A组）或3剂（B组）AD-MTx（1.6mg/0.4ml）或生理盐水（AD-NS）。A组猪在第2周安乐死（n=8），和B组猪在第3周安乐死(n=8)。使用玻璃体视网膜外科医生的隐性临床PVR评分（0-6）和隐性眼科病理学家的组织病理学PVR评分（0-8）来确定结果。
■意思是，联合临床和组织病理学评分(前后)用于确定组间的总体治疗效果.
■合并所有分级终点（临床+组织病理学）时，AD-MTx组的平均掩盖评分（±标准差）为8.0±2.3，而AD-NS对照组为9.9±2.0（P=0.05）。AD-MTx组的临床评分为3.88±1.2，AD-NS组为4.63±1.6（P=0.16）。前PVR的组织病理学评分在AD-MTx组为2.5±0.8，在AD-NS组为2.5±0.5(P=0.50)。AD-MTx组后PVR为1.63±1.6，AD-NS组为2.75±1.3（P=0.07）。当甲氨蝶呤给药频率在A组（2剂）与B组（3剂）比较时，平均得分为8.75和9.13（P=0.38），分别,暗示一个微不足道的差异。
■手术诱导PVR后，高风险,大型动物模型,与AD-NS相比,AD-MTx减少后部PVR形成。在第3周额外给药并没有改善结果。干预后，前PVR形成无差异。这种新型药物递送系统对减少PVR具有意义，值得进一步研究。
■专有或商业披露可以在参考文献之后找到。
■预期，随机化，介入,双面蒙面,控制,具有预定临床和组织病理学结果标准的大型动物研究。
■一半的猪被随机分配接受相同体积的气溶胶递送生理盐水（AD-NS），使用相同的递送系统和治疗间隔。
■在16只猪（8只雄性和8只雌性）中手术诱发增生性玻璃体视网膜病变，随机分配接受2剂（A组）或3剂（B组）AD-MTx（1.6mg/0.4ml）或生理盐水（AD-NS）。A组猪在第2周安乐死（n=8），和B组猪在第3周安乐死(n=8)。使用玻璃体视网膜外科医生的隐性临床PVR评分（0-6）和隐性眼科病理学家的组织病理学PVR评分（0-8）来确定结果。
■意思是，联合临床和组织病理学评分(前后)用于确定组间的总体治疗效果.
■合并所有分级终点（临床+组织病理学）时，AD-MTx组的平均掩盖评分（±标准差）为8.0±2.3，而AD-NS对照组为9.9±2.0（P=0.05）。AD-MTx组的临床评分为3.88±1.2，AD-NS组为4.63±1.6（P=0.16）。前PVR的组织病理学评分在AD-MTx组为2.5±0.8，在AD-NS组为2.5±0.5(P=0.50)。AD-MTx组后PVR为1.63±1.6，AD-NS组为2.75±1.3（P=0.07）。当甲氨蝶呤给药频率在A组（2剂）与B组（3剂）比较时，平均得分为8.75和9.13（P=0.38），分别,暗示一个微不足道的差异。
■手术诱导PVR后，高风险,大型动物模型,与AD-NS相比,AD-MTx减少后部PVR形成。在第3周额外给药并没有改善结果。干预后，前PVR形成无差异。这种新型药物递送系统对减少PVR具有意义，值得进一步研究。
■专有或商业披露可以在参考文献之后找到。
