Bernauer W, Thiel M A, Kurrer M, Heiligenhaus A, Rentsch K M, Schmitt A, Heinz C, Yanar A
Department of Ophthalmology, University of Zürich, Theaterstrasse 2, CH-8001 Zürich, Switzerland.
Br J Ophthalmol. 2006 Mar;90(3):285-8. doi: 10.1136/bjo.2005.082792.
To report a potential adverse effect of intensified treatment with sodium hyaluronate artificial tears.
Five cases of deep calcium deposition in the cornea associated with ocular surface disease and frequent use of hyaluronic acid artificial tears are described. All patients used one formulation of phosphate buffered hyaluronate eye drops when rapid calcification developed. All eyes required corneal graft surgery for visual rehabilitation. Specimens at keratoplasty were available for light microscopy and investigation by dispersive x ray analysis. The phosphate concentration in the medication used for topical treatment was measured and compared to alternative hyaluronate preparations.
Light microscopy showed dense mineralisation of the entire stroma. The crystalline deposits consisted of hydroxyapatite, Ca5(PO4)3OH. A 50-fold higher concentration of phosphate was measured in the sodium hyaluronate eye drops used for treatment (50.9 mmol/l) when compared with normal serum. The other hyaluronate formulations showed phosphate concentrations from <0.1 mmol/l to 10.9 mmol/l.
The hyaluronate artificial tear formulation "Hylo-Comod" favours the formation of insoluble crystalline calcium phosphate deposits in presence of epithelial keratopathy. This is because of its high phosphate concentration and typically frequent instillation. Manufacturers and prescribers should be aware that topical preparations may contain considerable amounts of phosphate which may lead to sight threatening corneal complications.
报告强化使用透明质酸钠人工泪液的潜在不良反应。
描述了5例与眼表疾病相关且频繁使用透明质酸人工泪液后角膜深层钙沉积的病例。当快速钙化发生时，所有患者均使用了一种磷酸盐缓冲的透明质酸钠滴眼液。所有患眼均需要进行角膜移植手术以恢复视力。角膜移植术中获取的标本可用于光学显微镜检查和X射线能谱分析。测量了用于局部治疗的药物中的磷酸盐浓度，并与其他透明质酸盐制剂进行了比较。
光学显微镜检查显示整个基质有致密矿化。结晶沉积物由羟基磷灰石Ca5(PO4)3OH组成。与正常血清相比，用于治疗的透明质酸钠滴眼液中的磷酸盐浓度高出50倍（50.9 mmol/L）。其他透明质酸盐制剂的磷酸盐浓度在<0.1 mmol/L至10.9 mmol/L之间。
在存在上皮性角膜病变的情况下，透明质酸钠人工泪液制剂“Hylo-Comod”有利于形成不溶性结晶磷酸钙沉积物。这是由于其高磷酸盐浓度和通常频繁的滴注。制造商和开处方者应意识到局部制剂可能含有大量磷酸盐，这可能导致威胁视力的角膜并发症。
