Fluocinolone Acetonide

Expert retina and uveitis specialists will help support the growth and innovation of ANI’s ophthalmology and retina franchise for a meaningful impact on patientsPRINCETON, N.J., Dec. 02, 2025 (GLOBE NEWSWIRE) -- ANI Pharmaceuticals, Inc. (“ANI” or the “Company”) (Nasdaq: ANIP) today announced that it has established The FutureVision Advisory Council to help guide the strategic advancement of its ophthalmology and retina franchise within the Company’s Rare Disease business. This steering committee includes seven retina specialists and three uveitis specialists recognized globally as leaders in their respective fields. “We have built a strong foundation for our ophthalmology and retina franchise and continue to look for opportunities to further positively impact patients,” said Nikhil Lalwani, President and Chief Executive Officer of ANI. “Establishing the FutureVision Advisory Council is an important step in enhancing the growth strategy for our current products and advancing the development of new offerings as we fulfill our mission of serving patients and improving lives.” ANI’s FutureVision Advisory Council is co-led by Arshad M. Khanani, MD, MA, FASRS, who serves as Principal Retina Advisor and Chair, and Peter Chang, MD, FACS who serves as Principal Uveitis Advisor and Chair. Dr. Khanani commented, "ANI has shown a strong and consistent dedication to the eye care community, and I am honored to serve as Co-Chair of this Advisory Council alongside such respected colleagues. Together, we have the opportunity to guide ANI’s future innovations toward the areas of greatest patient need." Dr. Chang added, “I look forward to working with the Uveitis Council members and the broader FutureVision Advisory Council as we advise the ANI team on the strategic opportunities to help more patients with ocular diseases.” Together, the FutureVision Advisory Council members bring decades of broad leadership experience in clinical research, innovation, and patient care. The FutureVision Advisory Council is comprised of the following two councils and members. Retina Council Principal Retina Advisor and Chair: Arshad M. Khanani, MD, MA, FASRS, Managing Partner, Director of Clinical Research, and Director of Fellowship at Sierra Eye Associates and Clinical Associate Professor at the University of Nevada, Reno School of MedicineAshkan M. Abbey, MD, FASRS, FAAO, Director of Clinical Research, Texas Retina AssociatesDavid A. Eichenbaum, MD, FASRS, Director of Research, Retina Vitreous Associates of Florida, and Collaborative Associate Professor, Morsani College of Medicine, University of South FloridaYasha S. Modi, MD, Vice Chair of Ophthalmology, Manhattan Eye, Ear & Throat Hospital, Northwell Health Christopher D. Riemann, MD, Cincinnati Eye Institute and Professor, University Of CincinnatiLejla Vajzovic, MD, FASRS, Professor of Ophthalmology, Pediatrics and Biomedical Engineering with Tenure, Duke University School of MedicineChristina Y. Weng, MD, MBA, Professor & Alice R. McPherson Retina Research Foundation Chair in Ophthalmology, Baylor College of Medicine Uveitis Council Principal Uveitis Advisor and Chair: Peter Y. Chang, MD, FACS, Partner and Co-President, Massachusetts Eye Research & Surgery InstitutionThomas Albini, MD, Professor of Clinical Ophthalmology and Robert Z. & Nancy J. Greene Chair in Ophthalmology, Bascom Palmer Eye Institute, University of Miami Health SystemRajiv Shah, MD, FASRS, Assistant Professor, Ophthalmology, Wake Forest University School of Medicine ANI’s Rare Disease ophthalmology portfolio includes ILUVIEN® (fluocinolone acetonide intravitreal implant), 0.19 mg (ILUVIEN), which is indicated for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids, and for the treatment of chronic non-infectious uveitis affecting the posterior segment (chronic NIU-PS). ILUVIEN is contraindicated in patients with ocular or periocular infections; glaucoma; and hypersensitivity to any components in the product. It also includes Purified Cortrophin® Gel (repository corticotropin injection USP) (Cortrophin Gel) which is indicated for the treatment of severe acute and chronic allergic and inflammatory conditions affecting different parts of the eye. Cortrophin Gel is contraindicated for intravenous administration. Please see additional important safety information for each product below. INDICATIONS FOR ILUVIENILUVIEN is a corticosteroid indicated for: the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure.the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. IMPORTANT SAFETY INFORMATION FOR ILUVIEN CONTRAINDICATIONS ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases.ILUVIEN is contraindicated in patients with glaucoma who have cup to disc ratios of greater than 0.8.ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product. WARNINGS AND PRECAUTIONS Intravitreal Injection-related Effects: Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased or decreased intraocular pressure, and choroidal or retinal detachments. Patients should be monitored following the intravitreal injection. Patients may experience temporary blurred vision after injection of the implant.Intraocular Pressure (IOP) Increase: Prolonged use of corticosteroids may result in the development of glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be routinely monitored during the course of the treatment.Cataracts: The use of corticosteroids may result in posterior subcapsular cataract formation.Delayed Corneal Wound Healing: The use of corticosteroids after cataract surgery may delay healing and increase the incidence of bleb formation.Corneal and Scleral Melting: Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of ophthalmic corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation of the globe.Bacterial Infections: Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. Acute purulent or parasitic infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.Viral Infections: Use of ocular corticosteroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.Fungal Infections: Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid application. Fungus invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.Risk of Implant Migration: Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber. ADVERSE REACTIONSDiabetic Macular EdemaOcular adverse reactions reported by greater than or equal to 1% of patients in the two combined 3-year clinical trials following injection of ILUVIEN for diabetic macular edema include: cataract (82%), myodesopsia (21%), eye pain (15%), conjunctival hemorrhage (13%), posterior capsule opacification (9%), eye irritation (8%), vitreous detachment (7%), conjunctivitis (4%), corneal oedema (4%), foreign body sensation in eyes (3%), eye pruritus (3%), ocular hyperaemia (3%), optic atrophy (2%), ocular discomfort (2%), photophobia (2%), retinal exudates (2%), anterior chamber cell (2%), and eye discharge (2%). Non-ocular adverse reactions reported by greater than or equal to 5% of patients include: anemia (11%), headache (9%), renal failure (9%), and pneumonia (7%) Increased Intraocular Pressure: IOP elevation greater than or equal to 10 mm Hg from baseline at any visit was seen in 34% of ILUVIEN patients versus 10% of sham patients. IOP elevation greater than or equal to 30 mm Hg was seen in 20% of ILUVIEN patients versus 4% of sham patients. 38% of the patients who received ILUVIEN were subsequently treated with IOP-lowering medications during the study versus 14% of sham patients. 5% of the patients who received ILUVIEN needed surgical intervention for elevated IOP versus 1% of sham patients Cataracts and Cataract Surgery: The incidence of cataract development in patients who had a phakic study eye was higher in the ILUVIEN group (82%) compared with sham (50%). The median time of cataract being reported as an adverse event was approximately 12 months in the ILUVIEN group and 19 months in the sham group. Among these patients, 80% of ILUVIEN subjects versus 27% of sham-controlled subjects underwent cataract surgery, generally within the first 18 months (median month 15 for both ILUVIEN group and for sham) of the studies. Chronic Non-Infectious Uveitis Affecting the Posterior Segment of the EyeOcular adverse reactions reported by greater than or equal to 1% of patients in the three combined clinical trials through 12 months following injection of fluocinolone acetonide intravitreal implant: cataract (56%), visual acuity reduced (15%), macular edema (11%), uveitis (10%), conjunctival hemorrhage (8%), eye pain (8%), hypotony of eye (7%), anterior chamber inflammation (5%), dry eye (4%), vitreous opacities (4%), conjunctivitis (4%), posterior capsule opacification (4%), ocular hyperemia (4%), vitreous haze (3%), foreign body sensation in eyes (3%), vitritis (3%), vitreous floaters (3%), eye pruritus (3%), conjunctival hyperemia (2%), ocular discomfort (2%), macular fibrosis (2%), glaucoma (2%), photopsia (2%), vitreous hemorrhage (2%), iridocyclitis (1%), eye inflammation (1%), choroiditis (1%), eye irritation (1%), visual field defect (1%), and lacrimation increased (1%). Non-ocular adverse reactions reported by greater than or equal to 2% of patients include: nasopharyngitis (5%), hypertension (3%), and arthralgia (2%). Increased Intraocular Pressure: IOP elevation greater than or equal to 10 mm Hg from baseline at any visit was seen in 22% of fluocinolone acetonide patients versus 12% of sham patients. IOP elevation greater than or equal to 30 mm Hg was seen in 12% of fluocinolone acetonide patients versus 3% of sham patients. 43% of the patients who received fluocinolone acetonide were subsequently treated with IOP-lowering medications during the study versus 41% of sham patients. 2% of the patients who received fluocinolone acetonide needed surgical intervention for elevated IOP versus 2% of sham patients. Please see full Prescribing Information for ILUVIEN. SELECT INDICATION FOR CORTROPHIN GEL Cortrophin Gel is a prescription medicine that is injected subcutaneously or intramuscularly. It is indicated for: Severe acute and chronic allergic and inflammatory conditions affecting the eye and its adnexa, such as allergic conjunctivitis, keratitis, iritis and iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, and anterior segment inflammation. IMPORTANT SAFETY INFORMATION FOR CORTROPHIN GELContraindications Cortrophin Gel is contraindicated for intravenous administration.Cortrophin Gel is contraindicated in patients who have any of the following conditions: scleroderma; osteoporosis; systemic fungal infections; ocular herpes simplex; recent surgery; history of or the presence of a peptic ulcer; congestive heart failure; hypertension; primary adrenocortical insufficiency; adrenocortical hyperfunction; or sensitivity to proteins derived from porcine sources. Warnings and Precautions Infections: Corticotropin therapy may increase susceptibility to infections and may mask the symptoms of infections.Adrenal insufficiency: Prolonged corticotropin therapy can increase the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by gradually reducing the corticotropin dosage. Hormone therapy should be reinstituted if stressful situations arise during discontinuation.Elevated blood pressure, salt and water retention, and hypokalemia: Corticotropin can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium or calcium.Masking symptoms of other diseases: Corticotropin may only suppress signs and symptoms of chronic disease without altering the natural course of disease.Psychiatric reactions: Psychic derangements may appear when corticotropin is used, ranging from euphoria, insomnia, mood swings, personality changes, and depression to psychosis. Existing conditions may be aggravated.Ophthalmic reactions: Prolonged use of corticotropin may produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerves.Immunogenicity potential: Prolonged administration of Cortrophin Gel may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH and Cortrophin Gel activity.Vaccination: Patients should not be vaccinated against smallpox while on corticotropin therapy. Other immunizations should be undertaken with caution due to possible neurologic complications and lack of antibody response.Use in patients with hypothyroidism and cirrhosis: There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis.Use in patients with latent tuberculosis or tuberculin reactivity: Closely observe for reactivation of the disease.Comorbid diseases: Corticotropin should be used with caution in patients with diabetes, abscess, pyogenic infections, diverticulitis, renal insufficiency, and myasthenia gravis.Growth and development: Carefully observe growth and development of infants and children on prolonged corticotropin therapy.Acute gouty arthritis: Treatment of acute gouty arthritis should be limited to a few days. Conventional concomitant therapy should be administered during corticotropin treatment and for several days after it is stopped.Drug interactions: Aspirin should be used cautiously with corticotropin in hypoprothrombinemia.Pregnancy: Since fetal abnormalities have been observed in animals, Cortrophin Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Adverse ReactionsAdverse reactions for Cortrophin Gel include fluid or sodium retention; muscle weakness; osteoporosis; peptic ulcer with possible perforation and hemorrhage; injection site reactions; impaired wound healing; hypertension; convulsions; headache; development of Cushingoid state; suppression of growth in children; and weight gain. These are not all the adverse reactions reported with Cortrophin Gel. Please see full Prescribing Information for Cortrophin Gel. About ANI Pharmaceuticals, Inc.ANI Pharmaceuticals, Inc. (Nasdaq: ANIP) is a diversified biopharmaceutical company committed to its mission of “Serving Patients, Improving Lives" by developing, manufacturing, and commercializing innovative and high-quality therapeutics. The Company is focused on delivering sustainable growth through its Rare Disease business, which markets novel products in the areas of ophthalmology, rheumatology, nephrology, neurology, and pulmonology; its Generics business, which leverages R&D expertise, operational excellence, and U.S.-based manufacturing; and its Brands business. For more information, visit www.anipharmaceuticals.com. Forward-Looking StatementsTo the extent any statements made in this release deal with information that is not historical, these are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, those relating to the commercialization and potential sales of the product and any additional product launches from the Company’s generic pipeline, 2025 guidance, other statements that are not historical in nature, particularly those that utilize terminology such as “anticipates,” “will,” “expects,” “plans,” “potential,” “future,” “believes,” “intends,” “continue,” the negatives thereof, or other words of similar meaning, derivations of such words and the use of future dates. Uncertainties and risks may cause the Company’s actual results to be materially different than those expressed in or implied by such forward-looking statements. Uncertainties and risks include, but are not limited to: the ability of our approved products, including Cortrophin Gel and ILUVIEN, , to achieve commercialization at levels of market acceptance that will continue to allow us to achieve continued profitability; our ability to complete or achieve any, or all of the intended benefits of acquisitions and investments, including the acquisition of Alimera, in a timely manner or at all; the limitation of our cash flow as a result of the indebtedness and liabilities incurred from the acquisition of Alimera; the risks that our acquisitions and investments, including the acquisition of Alimera, could disrupt our business and harm our financial position and operating results; delays and disruptions in production of our approved products, increased costs and potential loss of revenues if we need to change suppliers due to the limited number of suppliers for our raw materials, active pharmaceutical ingredients, expedients, and other materials; delays and disruptions in production of our approved products as a result of our reliance on single source third party contract manufacturing supply for certain of our key products, including Cortrophin Gel and ILUVIEN; delays or failure in obtaining and maintaining approvals by the FDA of the products we sell; changes in policy or actions that may be taken by the FDA, United States Drug Enforcement Administration and other regulatory agencies, and the focus of the current U.S. presidential administration, including among other things, drug recalls, regulatory approvals, facility inspections and potential enforcement actions; risks that we may face with respect to importing raw materials and delays in delivery of raw materials and other ingredients and supplies necessary for the manufacture of our products from both domestic and overseas sources due to supply chain disruptions or for any other reason, including increased costs due to tariffs; the ability of our manufacturing partners to meet our product demands and timelines; the impact of changes or fluctuations in exchange rates; our ability to develop, license or acquire, and commercialize new products; our obligations in agreements under which we license, develop or commercialize rights to products or technology from third parties and our ability to maintain such licenses; the level of competition we face and the legal, regulatory and/or legislative strategies employed by our competitors to prevent or delay competition from generic alternatives to branded products; our ability to protect our intellectual property rights; the impact of legislative or regulatory reform on the pricing for pharmaceutical products; the impact of any litigation to which we are, or may become, a party; our ability, and that of our suppliers, development partners, and manufacturing partners, to comply with laws, regulations and standards that govern or affect the pharmaceutical and biotechnology industries; our ability to maintain the services of our key executives and other personnel; the potential impact of new U.S. tax legislation on our business, including the One Big Beautiful Bill Act; and general business and economic conditions, such as inflationary pressures, geopolitical conditions, and other risks and uncertainties that are described in ANI’s Annual Report on Form 10-K, quarterly reports on Form 10-Q, and other periodic reports filed with the Securities and Exchange Commission. More detailed information on these and additional factors that could affect the Company’s actual results are described in the Company’s filings with the Securities and Exchange Commission (SEC), including its most recent annual report on Form 10-K and quarterly reports on Form 10-Q, and other periodic reports, as well as other filings with the SEC. All forward-looking statements in this news release speak only as of the date of this news release and are based on the Company’s current beliefs, assumptions, and expectations. The Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise. Investor Relations:Courtney Mogerley, Argot PartnersT: 646-368-8014E: ani@argotpartners.com Media Relations:Deborah Elson, Argot PartnersE: ani@argotpartners.com

治疗现状 黄褐斑是一种常见的获得性色素沉着性疾病，其顽固性和易复发性给患者带来长期困扰。由于黄褐斑涉及皮肤的色素问题，炎症问题，以及皮肤老化问题等多个方面，其治疗必然是系统性和综合性的。首先做好健康宣教，强调保湿修复皮肤屏障、严格注意防晒是治疗的前提；其次是系统查体、排查诱因，调整情绪睡眠、避免诱发因素等；治疗是以外用和口服为主，在色斑稳定的前提下，可视情况联合激光或化学剥脱等方法治疗。 认识到所有黄褐斑都是“混合型”的这一观点，为治疗提供多个潜在的靶点。目前已开发出作用于不同层面的新型药物，从经典靶向黑素生成途径，到作用于过度活跃的黑素细胞、减轻炎症和自由基产生，以及抑制黑素小体向角质形成细胞的转移。一些新药可能通过修复皮肤屏障或调节激素水平发挥作用，而另一些则靶向真皮脉管系统和肥大细胞。 外用药物 氢醌及三联疗法 氢醌（Hydroquinone）一直是黄褐斑治疗的金标准，临床研究表明，氢醌与防晒霜、维A酸、氨甲环酸等联用可显著改善黄褐斑。国外学者提出的Kligman三联疗法结合氢醌、维A酸和类固醇（如地塞米松），通过多靶点协同作用显著提升疗效：氢醌抑制黑色素生成，维A酸加速色素脱落，类固醇则减少治疗中的刺激性不良反应。然而，三联疗法因药物的副作用等问题，其在黄色人种治疗中的地位尚未明确，近来，国内上市了类似的三联组合药物，其市场前景值得期待。 壬二酸 壬二酸通过抑制酪氨酸酶活性减少黑色素生成，同时具有抗炎作用，可减轻炎症相关的色素沉着。还能促进角质层更新，加速表皮黑色素的脱落，从而改善肤色不均。临床研究显示，20%壬二酸乳膏对表皮型黄褐斑疗效显著，且耐受性良好，常见不良反应仅为轻微刺激或瘙痒。与氢醌相比，壬二酸安全性更高，更适合长期使用，尤其适用于对氢醌不耐受或担心色素反弹的患者。另外，其它经典皮肤美白剂：曲酸、熊果苷、烟酰胺、抗坏血酸依旧在黄褐斑治疗领域发挥作用。 外用氨甲环酸 外用氨甲环酸在黄褐斑治疗中通过局部渗透直接作用于色素沉着区域，抑制黑色素生成。其机制主要是减少纤溶酶原激活剂的活性，从而降低酪氨酸酶的活性，进而减少黑色素合成。外用制剂适用其优势在于局部作用，副作用较少，但疗效可能较口服稍弱，需要考虑剂型、促渗等问题，且需要长期坚持使用。已经有证据表明：新型氨甲环酸递送系统：脂质体/微针增强透皮吸收，可辅助4%氨甲环酸渗透率提升3倍，疗效优于单用氢醌，氨甲环酸皮内注射优于外用（MASI改善62.7% vs 4.2%）。 其它新型外用成分 研究证实参与黑素生成的基因（酪氨酸酶、TYRP1、TYRP2 和 MITF）在黄褐斑患者的皮损皮肤中表达上调，皮损黑素细胞显示出树突、线粒体、高尔基体和粗面内质网数量增加。这些发现表明，生物活性增强（而非细胞数量增加）是导致黄褐斑色素沉着过度的原因。因此，除了减少黑色素合成外，抑制黑素细胞的活性可能对改善黄褐斑更有效。传统的药物除了氢醌、熊果苷和脱氧熊果苷、亚油酸、抗坏血酸、N-乙酰基-4-S-半胱氨酰苯酚等，芦荟苦素、4-正丁基间苯二酚（Rucinol）、类黄酮、表没食子儿茶素没食子酸酯和鞣花酸、龙胆酸、羟基香豆素、肉桂酸、反义寡核苷酸等新型抑制黑素细胞活性的成分也显示了其应用的优势。 噻胺醇 (Thiamidol)是强效可逆酪氨酸酶抑制剂，有证据表明 0.2%噻胺醇疗效优于4%氢醌，MASI评分降幅更高（43% vs 33%）；新型的三联配方（噻胺醇+维A酸+激素）疗效优于传统Kligman经典三联（mMASI改善63% vs 39%）。 半胱胺 (Cysteamine)，可以抑制酪氨酸酶/过氧化物酶，上调谷胱甘肽，5%半胱胺乳膏疗效接近4%氢醌，但刺激性更低，长期使用无外源性褐黄病风险。 口服药物 口服氨甲环酸 口服氨甲环酸通过系统性作用抑制黑色素生成，抑制肥大细胞活化，减少血管增生，对顽固性黄褐斑，尤其是真皮型和混合型黄褐斑，具有显著疗效，对于活动期黄褐斑皮损患者可以考虑口服药物方式治疗。临床研究表明，口服治疗可显著改善色素沉着，且长期使用安全性较高。然而，口服治疗可能存在一定的系统性副作用，如胃肠道不适、月经紊乱等，需采取措施尽可能避免该药物的副作用，例如避开月经周期服药等，目前文献证实250mg bid × 12周 疗效优于500mg bid，且副作用减少，停药后复发率18-30%，需间歇性维持等。 其它口服药物 原花青素，从葡萄籽中提取的原花青素具有显著的抗氧化作用，多项研究表明它对黄褐斑有益。 碧萝芷 (Pycnogenol)， 是一种从法国海岸松树皮中提取的物质，具有抗酪氨酸酶活性、抗氧化和抗炎特性，并通过抑制血管内皮生长因子靶向黄褐斑的血管成分，口服制剂已被证实对黄褐斑有益。 口服鳞毛蕨提取物 (Oral Polypodium leucotomos)，鳞毛蕨 (Polypodium leucotomos, PLE*) 是一种热带蕨类植物，有潜在证据表明可作为黄褐斑的治疗方法。它是一种具有光保护活性的抗氧化剂，因此已被用于防晒霜或治疗光敏性疾病，如多形性日光疹。 化学剥脱 化学剥脱是治疗顽固性黄褐斑的有效方法，其通过促进表皮更新和色素脱落，显著改善皮肤色斑。常用剥脱剂如果酸（如甘醇酸、乳酸）、水杨酸和三氯醋酸，通过溶解角质层，加速黑色素细胞代谢，减少表皮色素沉积，同时刺激真皮胶原再生，改善皮肤质地，同时增强其他美白成分的渗透性。化学剥脱是黄褐斑综合治疗中的重要手段，兼具美白与焕肤双重效果，一般建议在色斑稳定期使用，对于作用时间和深度需要精准把控以减少并发症。 物理疗法 鉴于黄褐斑的复杂性，光声电等物理技术可能针对其发病机制的某一方面起作用，例如针对黄褐斑的色素异常，激光可以通过选择性光热作用理论，精准破坏黑色素颗粒而不损伤黑素细胞，促进色素代谢，显著改善色斑；激光也可以通过光调作用调控炎症改善色斑；另外，点阵CO₂激光、黄金微针点阵射频可以通过促进药物渗透、改善皮肤老化等方面改善黄褐斑；微针和微晶针（mesoneedling）均能有效改善表皮型黄褐斑患者的色素沉着，且安全性较高，其机制可能与微针刺激皮肤后诱导胶原生成、促进药物渗透以及调节黑色素代谢有关。光声电、微针等物理方法对于黄褐斑的疗效确切，但需要更多更高等级的循证医学证据。 外用药物 二甲双胍 在黄褐斑的治疗中，外用二甲双胍展现出一定的潜力。临床研究证实，30%的二甲双胍洗剂在治疗黄褐斑方面与传统的三重组合霜（TCC）疗效相当，且安全性更高。研究显示，二甲双胍通过下调MITF表达，进而抑制酪氨酸酶等黑色素生成蛋白的转录，发挥其美白作用。尽管治疗效果尚未达到显著水平，但其安全性和潜在的抗黑色素生成机制为其在黄褐斑治疗中的应用提供了新的思路。 富血小板血浆 在黄褐斑的治疗中，富血小板血浆（PRP）作为一种新兴疗法展现出一定的潜力。González-Ojeda等人的自控临床试验表明，PRP治疗能够显著改善黄褐斑患者的色素沉着，且安全性较高。其机制可能与PRP中富含的生长因子（如TGF-β）促进皮肤修复和调节黑色素生成有关。尽管PRP的疗效仍需进一步验证，但其作为一种局部治疗手段，为黄褐斑的治疗提供了新的方向，尤其适用于对传统疗法耐受性较差的患者。 总之，黄褐斑作为一种多因素疾病，其发病机制复杂，涉及黑色素生成、血管异常、氧化应激及炎症反应等多重病理过程。因此，单一治疗方法往往难以取得理想效果，联合治疗成为当前的主要策略。未来研究将更加注重靶向治疗和个性化方案的开发，以精准调控黄褐斑的病理进程，提高疗效并减少副作用。 总结与展望 当前对黄褐斑的整体认识 黄褐斑作为一种多因素驱动的色素沉着性疾病，对患者的生活质量构成了显著负面影响。近十年来，黄褐斑相关研究已从流行病学特征描述深入到发病机制解析与诊疗体系优化。当前研究已突破“单一色素异常”的传统认知框架，揭示出氧化应激，黑素合成亢进，黑素细胞下垂，基底膜受损，肥大细胞数量及血管分布增加等多重病理因素的交互作用，特别是对于表皮黑素细胞、角质形成细胞、真皮成纤维细胞、肥大细胞和血管内皮细胞之间复杂的相互作用对黄褐斑的影响是近年的研究热点。诊断层面以Wood灯、皮肤镜、反射式共聚焦显微镜等无创检测技术为主流手段，同时采用MASI评分系统量化评估等优化临床诊疗。中医诊疗指南进一步纳入中医辨证要素，形成西医病理定位与中医辨证相结合的诊断体系。在治疗上，黄褐斑作为具有慢性迁延性和复发性特征的疾病，除始终强调的严格光保护措施、外用药物等一线治疗方案外，联合疗法的方法逐渐受到重视，光声电技术联合药物或产品能够改善色斑。然而，现有手段仍面临复发率高、系统用药安全性风险等问题，亟需创新策略的突破。 黄褐斑领域未来发展方向展望 机制研究 未来黄褐斑领域的机制研究将聚焦于多维度病理网络的系统解析，包括深入研究表皮黑素细胞、角质形成细胞、真皮成纤维细胞、肥大细胞和血管内皮细胞之间复杂的相互作用，深化对真皮-表皮交互调控网络的认知，特别是KGF等因子介导的信号传导通路的研究。 在皮肤微生物调控层面，丙酸杆菌主导的皮肤菌群失调对于色素代谢的影响仍需进一步探究；黑色素细胞外泌体中特定miRNA的释放机制，以及自噬相关蛋白在黄褐斑皮损中表达异常的调控机制已被证实参与黑色素沉着过程，为黄褐斑的病理解析提供了全新的研究视角。此外，多组学技术的整合应用有望揭示MC1R等易感基因与氧化应激通路的交互关系。 新型干预策略 新型干预策略将向精准化与多靶点协同调控方向发展。在药物研发层面，已有研究表明靶向酪氨酸酶的新型抑制剂与抗氧化剂的联合递送系统可提升透皮效率并降低刺激性；物理治疗领域中，低能量Q开关Nd:YAG激光与皮秒技术的参数优化可有效降低反黑风险；而激光联合口服氨甲环酸的协同方案成为目前难治性病例的优选之一。黄金微针改善基底膜带损伤以及皮肤老化从而改善黄褐斑也开启了新的视野。此外，针对肠-皮轴调控的益生菌干预可能为预防复发提供新途径。 ✰ 文章内容仅用于学术探讨，供医疗专业人士阅读 排版：优麦美学 参考文献（上下滑动查看） 1. 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Lasers Med Sci. 2022;37(7):2879-2887. 刘华绪 主任医师 山东第一医科大学附属皮肤病医院 博士 主任医师 研究生导师 现任山东第一医科大学附属皮肤病医院（山东省皮肤病医院）激光美容科主任 主要从事激光诊疗在皮肤科的应用及基础研究 主持国家自然基金及科技部重点专项等三项，省自然基金等项目三项，发表论文70余篇，其中SCI收录30篇。 分 享 / 点 赞 / 收 藏 / 关 注 ↓↓