可降解的眼科靶向用药缓释系统

关于黄医生

当今最先进有效的眼部用药方法是定向缓释药物系统，黄振强医生正是这些系统的发明人和专利持有者。

黄医生是国际领先的眼科临床研究者以及眼科缓释药物的创始人。采用这些缓释系统研制的药物已在全球广泛应用。

黄医生居住在美国硅谷是第四代美籍华人，他期望把中国建成眼科药物及治疗眼病的的全球领军者。

本文简述眼科药物缓释系统的历史和现状，帮助眼科医生和研究人员了解最前沿的技术，挑战和机遇。

黄医生希望寻找志同道合中国合作伙伴，无论是研究人员，临床医生，医院还是医药企业，共同应对各类眼科疾病，比如：白内障，眼部创伤，青光眼，近视，感染，过敏，干眼，葡萄膜炎，老年黄斑变性等。

眼科药物缓释系统的发展历程

临床研究阶段

黄振强医生职业生涯的前三十年主要从事眼科临床研究，科研以及眼科教学工作。他在美国国家卫生部工作了12年，1970年担任国家眼科研究院的第一位临床主任，领导全球最尖端的眼科临床及研究工作。从1972年到1992年，黄医生在美国乔治敦大学医学院担任眼科教授，并担任文森特.伦巴蒂癌症研究中心（Vincent T. Lombardi Cancer Research Center ）的眼肿瘤部主任。

在三十年的临床研究期间，黄医生取得了令人瞩目的成绩：

· 第一个通过眼部注入TNF展示眼部肿瘤模型
· 第一个发现并定义视网膜色素和维他命A在致盲诱因中的作用
· 第一个进行角膜结膜炎和念珠菌感染病人的免疫重建
· 第一个在眼病治疗中进行免疫疗法
· 第一个发现氯霉素会引起视神经萎缩
· 第一个临床发现成人及儿童胱氨酸病是一种溶酶体紊乱现象
· 第一个发现男性眼科组织胞浆菌病的起因并制作出实验模型
· 第一个展现类癌瘤综合症的眼科反应

长期的临床研究让黄医生对眼科药物有惊人的发现：

图示：0.1%的地塞米松眼药水在眼前房水中的药物浓度

第一：传统的滴眼液的作用十分有限。虽然眼药水没有入侵性但作用也是有限的，因为眼角膜的屏障和眼部血管的吸收将药物被不断带走。黄医生的研究表明传统地塞米松滴眼液在眼部的持续时间不足两小时。
第二：眼部药物注射的作用也有限。黄医生通过在兔眼中注射各种染色剂以及药物来确定染色剂和药物在眼内保存的时间长短。“有些药物3小时后就消失了，有些11个小时后才消失”，他说“我意识到每种药物和眼睛存在各自的关系，但总体来说它们不能存在很长时间”。也就是说需要重复注射才能有效。

总而言之，眼科药物是一个尚未成熟的领域。眼科的未来发展不仅在于更高的手术技巧和新的化学制剂，也在于药物能够：
· 在眼部直接用药
· 在可控的时间内持续作用
· 可生物降解

专利药物研发阶段

凭借这种洞察力及深厚的化学功底，黄医生花了几十年时间发明并取得了一些列的专利，迄今为止这些专利成功构成为三个缓释系统/平台：
· 可降解的缓释植入剂
· 缓释注射悬浮液
· 缓释滴眼液

这三个平台都能够释放多种API（大分子及小分子活性药物），缓释时间从数天到数月不等，针对几乎所有的重大眼科疾病。

图示：双氯芬酸体外释放曲线，总释放量百分比

三个缓释系统的技术特点

A．可降解的缓释植入剂

这是一种将活性药物成分和可生物降解的聚合物相结合的微粒，持续释放活性药物一周至数周。 SURODEX™ 是黄医生在Oculex Pharmaceuticals 研发的第一个产品。在白内障手术后在眼前房植入一粒，在7-14天内缓慢释放地塞米松，消除术后炎症，取代传统的消炎类眼药水。该药物于1999年在中国成功注册上市。

Surodex和眼药水在体内试验中的地塞米松浓度比较

在白内障手术后在眼前房植入一粒

第二个产品是伴随使用的SUROQIN™, 它也是在白内障手术后植入眼前房，缓慢释放环丙沙星预防术后炎症。该药物于2001年在中国成功注册。

随后研制的OZURDEX®是一个放置于眼后节的缓释剂，在植入后的数月内持续释放地塞米松，可治疗糖尿病性黄斑水肿，黄斑水肿及非感染性葡萄膜炎。植入剂数月后完全降解，无需移除。

OZURDEX® 于2009年获得美国FDA批准，目前在包括中国在内的全世界范围销售，成为一个重要的眼科药物。

OZURDEX由黄医生在OCULEX公司开始研发，该公司于2003年被Allergan公司收购。

B．缓释注射悬浮液

这是可注射的缓释悬浮液。注射后立即开始释放药物，不同的剂型释放药物的时间可达数天或者数月，在眼前房或后房保持有效浓度的药物。

黄医生用该系统成功研制的第一个产品是Dexycu® - 9%的地塞米松注射悬浮液，白内障术后在眼前房注射一剂即可消除白内障术后的炎症，取代传统的消炎类眼药水。DEXYCU已在美国上市，并于2021年进入中国。

DEXYCU由黄医生在ICON BIOSCIENCE公司开始研发，该公司2018年被EyePoint 公司收购。

C．缓释注射悬浮液

黄医生最新发明的缓释系统是滴眼液。传统眼药水虽然容易使用，无入侵性，但因为眼部血管把药物不断冲走，需要反复频繁用药，病人遵守医嘱成为问题，同时因为频繁使用会产生副作用。

黄医生的缓释滴眼液解决了这些问题。一滴眼药水能够持续释放有疗效浓度的药物长达一周以上。运用这一技术研制的第一个药物目前正在美国进行临床试验。

这个缓释系统克服了眼部血管对药物的冲洗作用，使眼部用药更持续有效。因为眼药水的长效机制，施用一次即可，医生可以不依赖病人或家属的配合。这对于就医不方便的偏远地区和儿童尤为重要。

学术成就

March 2013 - Present

宾夕法尼亚州立大学获得科学物理化学学士学位。

March 2013 - Present

美国杰佛逊医学院。

March 2013 - Present

约翰霍普金斯大学Fellowship。

March 2013 - Present

宾夕法尼亚研究生医院（Pennsylvania Graduate Hospital）。

March 2013 - Present

宾夕法尼亚研究生医院眼科住院医师培训。

March 2013 - Present

美国军事病例研究所眼科博士后。

March 2013 - Present

发现成人及儿童的胱氨酸病是一种溶酶体紊乱现象。

March 2013 - Present

提出交感性眼炎是一种免疫反应。

March 2013 - Present

拥有五十多项专利。

March 2013 - Present

发现并定义了视网膜色素和维他命A在致盲诱因中的作用。

March 2013 - Present

试验发现眼组织胞浆菌病的起因，并制作出预防此疾病的动物模型。

March 2013 - Present

创建了第一个眼部肿瘤试验模型，并在试验模型上通过前房灌注防癌影响因子首次成功治疗眼部肿瘤。

学术论文

· Jennifer I. Lim, MD, Marcia Niec, BS, Jessica Sun MD, Vernon Wong, MD: Phase 1 Study: Combination Therapy Using a Single Injection of IBI 20089 and Ranibizumab as Needed Therapy for Neovascular AMD: 2-Year Results. ARVO May 4, 2015.

· Jennifer I. Lim MD, Marcia Niec BS, Vernon Wong MD: One Year Results of a Phase 1 Study of the Safety and Tolerability of Combination Therapy Using Sustained Release Intravitreal Triamcinolone Acetonide and Ranibizumab for Subfoveal Neovascular AMD. Retina, 2014

· INNOVATION IN RETINA. Dr. Vernon G. Wong: A Pioneer in Sustained-Release Therapy. After Ozurdex success, he seeks new challenges to tackle. Retinal Physician. May 1, 2012.

· Jennifer I. Lim, Anne E. Fung. Marrk Wieland. Dean Hung, Vernon G. Wong: Sustained-Release Intravitreal Liquid Drug Delivery Using Triamcinolone Acetonide for Cystoid Macular Edema in Retinal Vein Occlusion. Ophthalmology 118:1416-1422, 2011 Issue 7.

· Jennifer I. Lim MD, Dean Hung PhD, Anne E. Fung MD, Mark Wieland MD and Vernon Wong MD: One Year Results of Phase 1 Study Evaluating the Safety and Evidence of Efficacy of a Single Intravitreal Injection of the VerisomeTM Liquid Drug Delivery System for Sustained Release of Low-dose Triamcinolone (IBI-20089) in Eyes with Cystoid Macular Edema. ARVO May 2010

· Jennifer I. Lim MD1, Anne E. Fung, MD2, Mark Wieland MD3, Dean Hung PhD4, Vernon G. Wong MD: Phase 1 Study of a Novel Sustained Release Intravitreal Liquid Drug Delivery System (VerisomeTM) Containing Triamcinolone for Chronic CME. Retina Congress October 4, 2009. New York

· Fung A, Wieland MR, Wong VG, Hu M, Huang G, Karasina F: Verisome™, a New, Injectable, Sustained Release, Biodegradable, Intraocular Drug Delivery System Demonstrates Positive Clinical Safety and Efficacy. ASRS, October 14, 2008

· Miguel Pedroza-Seres, M.D. Nathan Grinberg, M.D., Francisco Martínez Castro, M.D., Ingrid Kane, M.D.* and Vernon Wong, M.D. *: Preliminary Results in the Treatment of Patients with Idiopathic Pars Planitis with a New Dexamethasone Delivery System. Pan American Assoc. Ophthal. Buenos Aires, Argentina, July 2001

· Lee KY and Wong VG: Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) in the Treatment of Severe Uveitis. Uveitis in the Third Meillennium. 143-147, 2000. Excerpta Medica International Congress Series 1204. Dodds EM and Couto CA, Editors.

· Chang DF and Wong VG: Two clinical trials of an intraocular steroid delivery system for cataract surgery. Tr Am Ophth Soc XCVII:261-279, 1999.

· Wong VG and Viola RS: Effect of rH tumor necrosis factor on experimental intraocular tumors. Cornea 10(2):131-135, 1991.

· Sery TW, Lee EY-HP, Lee W-H, Bookstein R, Wong VG, Shields J, Augsburger JJ, Donoso LA: Characteristics of two (2) new retinoblastoma cell lines Weri-Rb24 and Weri-Rb27. J Ped Ophthal and Strabismus 27(4):212-217, 1990.

· Wong VG and Viola R: Effect of rH TNF (Tumor Necrosis Factor) on VX2 Intraocular Tumor. Invest Ophthalmol Vis Sci (Suppl.) 30:59, 1989.

· Rao NA, Phillips TM, Wong VG, Sliwinski AJ, and Marak GE: Etiology of Scleritis. Immunology and Immunopathology of the Eye, Masson and Co., New York, 1985.

· Stump J and Wong VG: Diagnosis of Treatment of Cystinosis. Current Ocular Therapy, Vol. II, W.B. Saunders and Co., 1983.

· Davidson C, Green WR, Wong VG: Retinal atrophy-induced by intravitreous colchicine. Assoc for Research in Vision and Ophthalmol 24:301-311, 1983.

· Rao NA, Wong VG, and Lubow M: Experimental Optic Neuritis in Primates. Proceedings of ARVO, April-May, 1981. Invest Ophthalmol (Suppl.) 20:42, 1981.

· Rao NA and Wong VG: Etiology of sympathetic ophthalmia. Trans Ophthal Soc U.K. 101:357-360, 1981.

· Yamamoto GK and Wong VG: New concepts on metabolic abnormalities in corneal disease. Second World Congress on the Cornea. Contact and Intraocular Lens Medical J 6:346-353, 1980.

· Wong, VG, Marsden RR, and Liu YP: Cyclic nucleotides in retinoblastoma and malignant tissues: The role of phosphodiesterase, protein activator and retinal inhibitor. Ophthalmology Update, Univ. of Miami School of Medicine Oc. Path. Update, Masson Publishing Company USA, Chapter 15, p. 245-451, 1980.

· Wong VG: Current Ocular Therapy. Sec. 19, Choroid Sympathetic Ophthalmia, Fraunfelder and Roy, W.B. Saunders Co., Philadelphia-London-Toronto, pp. 338-340, 1980.

· Wong VG, Green WR, Liu YP, and Marsden ER: Experimental intraocular malignancy: The effect of intramural perfusion. Am Ophthal Soc LXXVII:63-79.

· Liu YP, Wong VG, and Lin YM: A heat-stable protein inhibitor of cyclic 3',5'-nucleotide phosphodiesterase. Life Science 583:273-278, 1980.

· Yamamoto GK, Schulman J, Schneider J, and Wong VG: Long-term ocular changes in cystinosis: Observations in renal transplant recipients. J Ped Ophthal Strabis 16:21-25, 1979.

· Wong VG, Green WR, and McMaster PRB: Rhodopsin and blindness. Am Ophthal Soc LXXV:272-284, 1977.

· London WT, Levitt NH, Kent SG, Wong VG, and Sever JL: Congenital cerebral and ocular malformations induced in Rhesus monkeys by Venezuelan Equine Encephalitis (VEE) Virus. Teratology 16:285-296, 1977.

· Liu YP, Wong VG, and Chabner BA: Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma. J Natl Cancer Inst 59:1605-1609, 1977.

· Wong VG: Vision mediator could play part in sight loss. JAMA 236-338, 1976.

· Wong VG: Ocular manifestations in cystinosis: The eye and inborn errors of metabolism. The National Foundation - March of Dimes, Birth Defects: Original Articles Series, vol. XII, Alan R. Liss, Inc, New York, NY (Publisher), November 13, 1976.

· McMaster PRB, Wong VG, and Owens JD: The propensity of different strains of guinea pigs to develop experimental autoimmune uveitis. Modern Problems in Ophthalmology 16:62-71, 1976.

· Limaye SR, Wong VG, and DeLaey JJ: Juvenile juxtapapillary hemorrhagic choroiditis. Documenta Ophthalmologica Proceedings Series, International Symposium on Fluorescein Angiography, JJ DeLaey (Ed) 9:347-352, 1976.

· Horton WA, Wong VG, and Eldridge R: Von Hippel-Lindau Disease: Clinical and pathological manifestations in nine families with 50 affected members. Arch Inter Med 136:769-777, 1976.

· Wong VG, Kwon-Chung KJ, and Hill WB: Koch's Postulates and Experimental Ocular Histoplasmosis. Ocular Histoplasmosis International Ophthalmology Clinics, vol. 15:139-145, no. 3, Fall 1975; TF Schlaegel (Ed), Little, Brown and Co.

· Wong VG, Green WR, McMaster PRB, and Johnson DK: Rhodopsin and autoimmune blindness in primates. Trans Penna Acad of Ophthal and Otolaryngol 28:13-137, 1975.

· Wong VG, Green WR, Kuwabara T, McMaster PRB, and Cameron TP: Homologous retinal outer segment immunization in primates. Arch Ophthal 93:509-513, 1974.

· Wong VG, Green WR, Kuwabara T, McMaster P, and Cameron TP: "Homologous Retinal Outer Segment Immunization in Primates." Trans Am Ophthal Soc 72:184, 1974.

· Wong VG and Kirkpatrick CH: Immune reconstruction in keratoconjunctivitis and superficial candidiasis: The role of lymphocytic transfusion and transfer factor. Arch Ophthal 92:335-339, 1974.

· Schneider JA, Verroust FM, Kroll WA, Garvin AM, Horger EO, Wong VG, Spear SG, Jacobson C, Pellett OL, and Becker FLA: The prenatal diagnosis of cystinosis. New Eng J Med 290:878-882, 1974.

· Sanderson PO, Kuwabara T, Stark WJ, Wong VG, and Collins EM: Cystinosis: A clinical, histopathologic and ultrastructural study. Arch Ophthal 91:270-274, 1974.

· Atkinson A, Sanders MD, and Wong VG: Vitreous hemorrhage in tuberous sclerosis. Report of two cases. Brit J Ophthal 57:773-779.

· Wong VG: The Eye and Cystinosis. Schulum JD (Ed), Cystinosis, DHEW Publication No. (NIH) 72-249, U.S. Dept. Health, Education, and Welfare, U.S. Gov't Printing Office, Washington, D.C. 20402, 1973.

· Wong VG: Kwon-Chung KJ, Green WR, Anderson RR, Collins EM, Hill WB: Focal Choroidopathy in Experimental Ocular Histoplasmosis. Transaction Am Ophthal and Otolaryn 77:769-77, 1973.

· Wong VG: Closing in on Histoplasma capsulatum. JAMA 223:1215, 1973.

· Wong VG and Kirkpatrick CH: Immunologic reconstitution in a patient with keratoconjunctivitis, superficial candidiasis, and hypoparathyroidism: The role immunocompetent lymphocyte transfusion and transfer factor. Am Ophthal Soc 1973 LXXI:254-271, 1973.

· Wong VG: Immunosuppressive agents in ophthalmology. In Leopold I (Ed): Ocular Therapy, vol. 5, St. Louis, CV Mosby, 1972.

· Wong VG: Immunosuppressive Agents in Ophthalmology. In Leopold IH (Ed), Symposium on Ocular Therapy, vol. V, The C.V. Mosby Company, St. Louis, 1972.

· Wong VG: Focal Choroidopathy in Experimental Ocular Histoplasmosis. Thesis for the American Ophthalmological Society, Feb. 1972.Steinberg AD, Plotz PH, Wolff SH, Wong VG, Agus SG, and Decker JL: Cytotoxic Drugs in Treatment of Non-malignant Diseases. Annals of Int Med, April 1972.

· Wong VG, Anderson R, and O'Brien P: Sympathetic ophthalmia and lymphocytic transformation. Amer J Ophthal 72:960-966, 1971.

· Wong VG, Anderson R, and McMaster PRB: Endogenous immune uveitis. Arch Ophthal 85:93-102, 1971.

· Newsome DA, Wong VG, Cameron TP, and Anderson R: "Steroid-induced" mydriasis and ptosis. Invest Ophthal 10:429-434, 1971.

· Minas T, and Wong VG: Ocular Inflammation. In Tasman W (Ed): Retinal Diseases in Children, New York, Harper and Rowe, pp. 207-221, 1971.

· Knopf H, Blacklow NR, Glassman MI, Cline WL, and Wong VG: Antibody in tears following intranasal vaccination with inactivated virus: II. Enhancement of tear antibody by production by the use of polyinosinic: polycytidilic (poly I:C). Invest Ophthal 10:750-759, 1971.

· Knopf H, Blacklow NR, Glassman MI, Cline WL, and Wong VG: Antibody in tears following intranasal vaccination with inactivated virus: III. Role of tear and serum antibody in experimental vaccinia conjunctivitis. Invest Ophthal 10:760-769, 1971.

· Wong VG: Current status of immunosuppressive therapy in ophthalmology. In H Kaufman (Ed): Ocular Anti-Inflammatory Therapy. Springfield, Charles C. Thomas, pp. 197-204, 1970.

· Wong VG, Schulman JD, and Seegmiller JE: Conjunctival biopsy for the biochemical diagnosis of cystinosis: A simple and rapid method. Amer J Ophthal 70:278-281, 1970.

· Wong VG, Kuwabara T, Brubaker R, Olson W, Schulman JD, and Seegmiller JE: Intralysomal cystine crystals in cystinosis. Invest Ophthal 9:73-88, 1970.

· Schulman JD, Wong VG, Olson W, and Seegmiller JE: Phagolysomal site of crystalline deposits in cystinosis as shown by ferritin uptake. Arch Path 90:259-264, 1970.

· Schulman JD, Wong VG, Kuwabara T, Bradley KH, and Seegmiller JE: Intracellular cystine content of leukocyte populations in cystinosis. Arch Intern Med 125:660-664, 1970.

· Schulman JD, Wong VG, Bradley K, Seegmiller JE: A simple technique for the biochemical diagnosis of cystinosis. J Pediat Ophthal 76:289-293, 1970.

· Brubaker RF, Wong VG, Schulman JD, Seegmiller JE, and Kuwabara T: Benign cystinosis: The clinical, biochemical, and morphologic findings in a family with two affected siblings. Amer J Med 49:546-550, 1970.

· Bowen RA, Hassard DT, Wong VG, Delellis RA, and Glenner GG: Lattice dystrophy of the cornea: A variety of amyloidosis. Amer J Ophthal 70:822-825, 1970.

· Wong VG: Immunosuppressive therapy of ocular inflammatory diseases. Arch Ophthal 81:628-637, 1969.

· Wong VG: Immunosuppressive agents in ophthalmology. Survey Ophthal 13:290-297, 1969.

· Schneider JA, Wong VG, and Seegmiller JE: The early diagnosis of cystinosis. J Pediat 74:114-116, 1969.

· Giles CL and Wong VG: Occurrence of adult cystinosis in childhood. J Pediat Ophthal 80:195-197, 1969.

· Wong VG and Bodey G: Hemorrhagic retinoschisis in aplastic anemia. Arch Ophthal 80:433-435, 1968.

· Seegmiller JE, Friedman T, Harrison HE, Wong VG, and Schneider JA: Cystinosis - Combined Staff Conference at the National Institutes of Health. Ann Int Med 68:883-905, 1968.

· Schneider JA, Wong VG, Bradley K, and Seegmiller J: Biochemical comparisons of the adult and childhood forms of cystinosis. New Eng J Med 279:1253-1257, 1968.

· Frazier PD and Wong VG: Cystinosis: Histologic and crystallographic examination of crystals in eye tissues. Arch Ophthal 80:87-91, 1968.

· Wong VG, Lietman PS, and Seegmiller JE: Alteration of pigment epithelium in cystinosis. Arch Ophthal 77:361-369, 1967.

· Wong VG and Melmon K: Ophthalmic manifestations of the carcinoid flush. New Eng J Med 277:406-409, 1967.

· Wong VG and McFarlin D: Primary familial amyloidosis. Arch Ophthal 78:208-213, 1967.

· Wong VG and Collier RH: Maintenance of the anterior chamber during anterior segment surgery. Arch Ophthal 77:384-386, 1967.

· Albert D, Wong VG, and Henderson E: Ocular complications of vincristine therapy. Arch Ophthal 78:709-713, 1967.

· Wong VG, Hersh EM, and McMaster PRB: Treatment of a presumed case of sympathetic ophthalmia with methotrexate. Arch Ophthal 76:66-76, 1966.

· Lietman PS, Frazier D, Wong VG, Shatton D, and Seegmiller JE: Adult cystinosis - A benign disorder. Amer J Med 40:511-517, 1966.

· Hersh EM, Wong VG, and Freireich EJ: Inhibition of the local inflammatory response in man by antimetabolites. Blood 27:38-48, 1966.

· Hersh EM, Wong VG, and Freirech EJ: Hepatotoxic effects of methotrexate. Cancer 19:600-606, 1966.

· Giles CL, Kaufman HE, and Wong VG: The use of antimetabolites in Ophthalmology. Amer J Med Sci 251:239-241, 1966.

· Wong VG and Hersh EM: Methotrexate in the therapy of cyclitis. Trans Amer Acad Ophthal, Otolaryng 69:279-293, 1965.

· Wong VG and Collins E: Optic atrophy in cystic fibrosis of the pancreas. Amer J Ophthal 59:763-769, 1965.

· Hersh EM, Carbone PP, Wong VG, and Freireich EJ: Inhibition of the primary immune response in many bh antimetabolites. Cancer Res 25:1177-1181, 1965.

· Wong VG and Macri FJ: Vasculature of the cat eye. Arch Ophthal 72:351-358, 1964.

· Lietman PS, di Sant'Agnese PA, and Wong VG: Optic neuritis in cystic fibrosis of the pancreas. Role of chloramphenicol therapy. JAMA 189:924-927, 1964.

· Wong VG, Lecombe M, Beizer L, Okuda K, and Chow BF: Effect of hog intrinsic factor on the absorption of coenzyme form of vitamin B-12 (5, 6-dimethylbenzmimi-dazolylcobimine). Amer J Clin Nutr 20:134-136, 1962.

· Wong VG, Yeh S, and Chow BF: Tissue retention and urinary excretion of injected vitamin B-12 and its coenzyme in the rat. Proc Soc Exp Biol Med 19:145, 1960.

· Davis RL, O'Connor J, Wong VG, Lawton AH, and Chow BF: Metabolic studies of vitamin B-12 (Depinar). Proc Soc Exp Biol Med 101:211-214, 1959.

· Chow BF, Prystowsky H, Hellegers AE, and Wong VG: Studies of the absorption of vitamin B-12 in human pregnancy with special reference to the effect of D-sorbitol. Am J Obstet Gynec 76:91-95, 1958.

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”黄医生温言软语，脚踏实地，正是他一系列奇迹性的成就使他几乎以一己之力成功研制了缓释植入剂Ozurdex®, 如今已经成为视网膜专家用于治疗与RVO相关黄斑水肿和非传染性葡萄膜炎的常规药物。“
— Retinal Physician 高级特约编辑 Jerry Hezner, MD

“防盲基金会第七届年会上将“防盲先驱奖”这一殊荣授予黄振强医生。颁奖仪式于6月5日在旧金山四季酒店举行，颁奖晚宴在黑暗中进行，这一独一无二的颁奖方式是为了让赴宴者体验全盲人群所面临的挑战。”
— 加利福尼亚州桑尼维尔 BUSINESS WIRE

“理想的眼科手术后的药物系统应该是能够有效地将药物输入眼部，并在足够长的时间内保持足够的药物浓度；通过将药效局限在靶向部位使得用药更安全，副作用更小；足够长效从而取代术后的眼药水；但同时药物作用时间足够短避免出现副作用或过敏。我们希望尽量减少病人对药物的使用，遵医嘱等方面的介入。理想的术后药物应该是价廉的….. Surodex 可谓这种产品的典范。Oculex 制药公司是由黄振强在硅谷联合创立的一家生物科技公司。Oculex 研制了一个可缓释的眼内药物缓释系统。这个小小的颗粒是由可生物降解的辅料组成，在手术结束时放置在眼前房。和辅料融合的药物以特定地的速度缓慢释放直至辅料完全降解。根据不同的配比，药物的释放时间可以短到一周，长至一年不等。”
— 美国加州大学眼科临床教授 David F. Chang, MD

未来及中国

黄医生仍然在不断地优化他的缓释技术，并将其应用于眼科之外的其它医学领域。带着对中国及中国人民深厚感情，黄医生毕生的希望是中国成为世界一流的眼科药物发展中心。他在中国建立了办公室，并希望通过和中国的临床医生，药物公司，研究机构，投资公司，医院或个人的合作实现梦想。

我们希望了解您对眼科缓释技术的想法和建议，感谢参与问卷调查。点击进入

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黄振强医生 Dr. Vernon G. Wong, M.D.

关于黄医生

黄振强医生职业生涯的前三十年主要从事眼科疾病的实验室及临床研究及教学工作。

眼科药物缓释系统的发展历程

临床研究阶段

在三十年的临床研究期间，黄医生取得了令人瞩目的成绩：

长期的临床研究让黄医生对眼科药物有惊人的发现：

专利药物研发阶段

三个缓释系统的技术特点

A．可降解的缓释植入剂

Surodex和眼药水在体内试验中的地塞米松浓度比较

在白内障手术后在眼前房植入一粒

第二个产品是伴随使用的SUROQIN™, 它也是在白内障手术后植入眼前房，缓慢释放环丙沙星预防术后炎症。该药物于2001年在中国成功注册。

随后研制的OZURDEX®是一个放置于眼后节的缓释剂，在植入后的数月内持续释放地塞米松，可治疗糖尿病性黄斑水肿，黄斑水肿及非感染性葡萄膜炎。植入剂数月后完全降解，无需移除。

OZURDEX® 于2009年获得美国FDA批准，目前在包括中国在内的全世界范围销售，成为一个重要的眼科药物。

B．缓释注射悬浮液

这是可注射的缓释悬浮液。注射后立即开始释放药物，不同的剂型释放药物的时间可达数天或者数月，在眼前房或后房保持有效浓度的药物。

黄医生用该系统成功研制的第一个产品是Dexycu® - 9%的地塞米松注射悬浮液，白内障术后在眼前房注射一剂即可消除白内障术后的炎症，取代传统的消炎类眼药水。DEXYCU已在美国上市，并于2021年进入中国。

C．缓释注射悬浮液

黄医生最新发明的缓释系统是滴眼液。传统眼药水虽然容易使用，无入侵性，但因为眼部血管把药物不断冲走，需要反复频繁用药，病人遵守医嘱成为问题，同时因为频繁使用会产生副作用。

黄医生的缓释滴眼液解决了这些问题。一滴眼药水能够持续释放有疗效浓度的药物长达一周以上。运用这一技术研制的第一个药物目前正在美国进行临床试验。

这个缓释系统克服了眼部血管对药物的冲洗作用，使眼部用药更持续有效。因为眼药水的长效机制，施用一次即可，医生可以不依赖病人或家属的配合。这对于就医不方便的偏远地区和儿童尤为重要。

学术成就

宾夕法尼亚州立大学获得科学物理化学学士学位。

美国杰佛逊医学院。

约翰霍普金斯大学Fellowship。

宾夕法尼亚研究生医院（Pennsylvania Graduate Hospital）。

宾夕法尼亚研究生医院眼科住院医师培训。

美国军事病例研究所眼科博士后。

发现成人及儿童的胱氨酸病是一种溶酶体紊乱现象。

提出交感性眼炎是一种免疫反应。

拥有五十多项专利。

发现并定义了视网膜色素和维他命A在致盲诱因中的作用。

试验发现眼组织胞浆菌病的起因，并制作出预防此疾病的动物模型。

创建了第一个眼部肿瘤试验模型，并在试验模型上通过前房灌注防癌影响因子首次成功治疗眼部肿瘤。

学术论文

· Jennifer I. Lim, MD, Marcia Niec, BS, Jessica Sun MD, Vernon Wong, MD: Phase 1 Study: Combination Therapy Using a Single Injection of IBI 20089 and Ranibizumab as Needed Therapy for Neovascular AMD: 2-Year Results. ARVO May 4, 2015.

· Jennifer I. Lim MD, Marcia Niec BS, Vernon Wong MD: One Year Results of a Phase 1 Study of the Safety and Tolerability of Combination Therapy Using Sustained Release Intravitreal Triamcinolone Acetonide and Ranibizumab for Subfoveal Neovascular AMD. Retina, 2014

· INNOVATION IN RETINA. Dr. Vernon G. Wong: A Pioneer in Sustained-Release Therapy. After Ozurdex success, he seeks new challenges to tackle. Retinal Physician. May 1, 2012.

· Jennifer I. Lim, Anne E. Fung. Marrk Wieland. Dean Hung, Vernon G. Wong: Sustained-Release Intravitreal Liquid Drug Delivery Using Triamcinolone Acetonide for Cystoid Macular Edema in Retinal Vein Occlusion. Ophthalmology 118:1416-1422, 2011 Issue 7.

· Jennifer I. Lim MD1, Anne E. Fung, MD2, Mark Wieland MD3, Dean Hung PhD4, Vernon G. Wong MD: Phase 1 Study of a Novel Sustained Release Intravitreal Liquid Drug Delivery System (VerisomeTM) Containing Triamcinolone for Chronic CME. Retina Congress October 4, 2009. New York

· Fung A, Wieland MR, Wong VG, Hu M, Huang G, Karasina F: Verisome™, a New, Injectable, Sustained Release, Biodegradable, Intraocular Drug Delivery System Demonstrates Positive Clinical Safety and Efficacy. ASRS, October 14, 2008

· Lee KY and Wong VG: Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS) in the Treatment of Severe Uveitis. Uveitis in the Third Meillennium. 143-147, 2000. Excerpta Medica International Congress Series 1204. Dodds EM and Couto CA, Editors.

· Chang DF and Wong VG: Two clinical trials of an intraocular steroid delivery system for cataract surgery. Tr Am Ophth Soc XCVII:261-279, 1999.

· Wong VG and Viola RS: Effect of rH tumor necrosis factor on experimental intraocular tumors. Cornea 10(2):131-135, 1991.

· Sery TW, Lee EY-HP, Lee W-H, Bookstein R, Wong VG, Shields J, Augsburger JJ, Donoso LA: Characteristics of two (2) new retinoblastoma cell lines Weri-Rb24 and Weri-Rb27. J Ped Ophthal and Strabismus 27(4):212-217, 1990.

· Wong VG and Viola R: Effect of rH TNF (Tumor Necrosis Factor) on VX2 Intraocular Tumor. Invest Ophthalmol Vis Sci (Suppl.) 30:59, 1989.

· Rao NA, Phillips TM, Wong VG, Sliwinski AJ, and Marak GE: Etiology of Scleritis. Immunology and Immunopathology of the Eye, Masson and Co., New York, 1985.

· Stump J and Wong VG: Diagnosis of Treatment of Cystinosis. Current Ocular Therapy, Vol. II, W.B. Saunders and Co., 1983.

· Davidson C, Green WR, Wong VG: Retinal atrophy-induced by intravitreous colchicine. Assoc for Research in Vision and Ophthalmol 24:301-311, 1983.

· Rao NA, Wong VG, and Lubow M: Experimental Optic Neuritis in Primates. Proceedings of ARVO, April-May, 1981. Invest Ophthalmol (Suppl.) 20:42, 1981.

· Rao NA and Wong VG: Etiology of sympathetic ophthalmia. Trans Ophthal Soc U.K. 101:357-360, 1981.

· Yamamoto GK and Wong VG: New concepts on metabolic abnormalities in corneal disease. Second World Congress on the Cornea. Contact and Intraocular Lens Medical J 6:346-353, 1980.

· Wong VG: Current Ocular Therapy. Sec. 19, Choroid Sympathetic Ophthalmia, Fraunfelder and Roy, W.B. Saunders Co., Philadelphia-London-Toronto, pp. 338-340, 1980.

· Wong VG, Green WR, Liu YP, and Marsden ER: Experimental intraocular malignancy: The effect of intramural perfusion. Am Ophthal Soc LXXVII:63-79.

· Liu YP, Wong VG, and Lin YM: A heat-stable protein inhibitor of cyclic 3',5'-nucleotide phosphodiesterase. Life Science 583:273-278, 1980.

· Yamamoto GK, Schulman J, Schneider J, and Wong VG: Long-term ocular changes in cystinosis: Observations in renal transplant recipients. J Ped Ophthal Strabis 16:21-25, 1979.

· Wong VG, Green WR, and McMaster PRB: Rhodopsin and blindness. Am Ophthal Soc LXXV:272-284, 1977.

· London WT, Levitt NH, Kent SG, Wong VG, and Sever JL: Congenital cerebral and ocular malformations induced in Rhesus monkeys by Venezuelan Equine Encephalitis (VEE) Virus. Teratology 16:285-296, 1977.

· Liu YP, Wong VG, and Chabner BA: Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma. J Natl Cancer Inst 59:1605-1609, 1977.

· Wong VG: Vision mediator could play part in sight loss. JAMA 236-338, 1976.

· Wong VG: Ocular manifestations in cystinosis: The eye and inborn errors of metabolism. The National Foundation - March of Dimes, Birth Defects: Original Articles Series, vol. XII, Alan R. Liss, Inc, New York, NY (Publisher), November 13, 1976.

· McMaster PRB, Wong VG, and Owens JD: The propensity of different strains of guinea pigs to develop experimental autoimmune uveitis. Modern Problems in Ophthalmology 16:62-71, 1976.

· Limaye SR, Wong VG, and DeLaey JJ: Juvenile juxtapapillary hemorrhagic choroiditis. Documenta Ophthalmologica Proceedings Series, International Symposium on Fluorescein Angiography, JJ DeLaey (Ed) 9:347-352, 1976.

· Horton WA, Wong VG, and Eldridge R: Von Hippel-Lindau Disease: Clinical and pathological manifestations in nine families with 50 affected members. Arch Inter Med 136:769-777, 1976.

· Wong VG, Kwon-Chung KJ, and Hill WB: Koch's Postulates and Experimental Ocular Histoplasmosis. Ocular Histoplasmosis International Ophthalmology Clinics, vol. 15:139-145, no. 3, Fall 1975; TF Schlaegel (Ed), Little, Brown and Co.

· Wong VG, Green WR, McMaster PRB, and Johnson DK: Rhodopsin and autoimmune blindness in primates. Trans Penna Acad of Ophthal and Otolaryngol 28:13-137, 1975.

· Wong VG, Green WR, Kuwabara T, McMaster PRB, and Cameron TP: Homologous retinal outer segment immunization in primates. Arch Ophthal 93:509-513, 1974.

· Wong VG, Green WR, Kuwabara T, McMaster P, and Cameron TP: "Homologous Retinal Outer Segment Immunization in Primates." Trans Am Ophthal Soc 72:184, 1974.

· Wong VG and Kirkpatrick CH: Immune reconstruction in keratoconjunctivitis and superficial candidiasis: The role of lymphocytic transfusion and transfer factor. Arch Ophthal 92:335-339, 1974.

· Schneider JA, Verroust FM, Kroll WA, Garvin AM, Horger EO, Wong VG, Spear SG, Jacobson C, Pellett OL, and Becker FLA: The prenatal diagnosis of cystinosis. New Eng J Med 290:878-882, 1974.

· Sanderson PO, Kuwabara T, Stark WJ, Wong VG, and Collins EM: Cystinosis: A clinical, histopathologic and ultrastructural study. Arch Ophthal 91:270-274, 1974.

· Atkinson A, Sanders MD, and Wong VG: Vitreous hemorrhage in tuberous sclerosis. Report of two cases. Brit J Ophthal 57:773-779.

· Wong VG: The Eye and Cystinosis. Schulum JD (Ed), Cystinosis, DHEW Publication No. (NIH) 72-249, U.S. Dept. Health, Education, and Welfare, U.S. Gov't Printing Office, Washington, D.C. 20402, 1973.

· Wong VG: Kwon-Chung KJ, Green WR, Anderson RR, Collins EM, Hill WB: Focal Choroidopathy in Experimental Ocular Histoplasmosis. Transaction Am Ophthal and Otolaryn 77:769-77, 1973.

· Wong VG: Closing in on Histoplasma capsulatum. JAMA 223:1215, 1973.

· Wong VG and Kirkpatrick CH: Immunologic reconstitution in a patient with keratoconjunctivitis, superficial candidiasis, and hypoparathyroidism: The role immunocompetent lymphocyte transfusion and transfer factor. Am Ophthal Soc 1973 LXXI:254-271, 1973.

· Wong VG: Immunosuppressive agents in ophthalmology. In Leopold I (Ed): Ocular Therapy, vol. 5, St. Louis, CV Mosby, 1972.

· Wong VG: Immunosuppressive Agents in Ophthalmology. In Leopold IH (Ed), Symposium on Ocular Therapy, vol. V, The C.V. Mosby Company, St. Louis, 1972.

· Wong VG: Focal Choroidopathy in Experimental Ocular Histoplasmosis. Thesis for the American Ophthalmological Society, Feb. 1972.Steinberg AD, Plotz PH, Wolff SH, Wong VG, Agus SG, and Decker JL: Cytotoxic Drugs in Treatment of Non-malignant Diseases. Annals of Int Med, April 1972.

黄振强医生
Dr. Vernon G. Wong, M.D.