Moller-Pedersen T, Cavanagh H D, Petroll W M, Jester J V
Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.
Ophthalmology. 2000 Jul;107(7):1235-45. doi: 10.1016/s0161-6420(00)00142-1.
To evaluate the mechanism(s) producing refractive instability and corneal haze development after photorefractive keratectomy (PRK).
Prospective, nonrandomized, comparative case series, self-controlled.
Seventeen eyes of 17 patients with low- to moderate-grade myopia (-2.88 to -9.13 diopters [D]) were included.
Surgical intervention was a standardized, 6-mm diameter PRK procedure using the Meditec MEL 60 excimer laser (Aesculap-Meditec, Heroldsberg, Germany). The photoablation center was evaluated before surgery and at 1, 3, 6, 9, and 12 months after PRK using rapid, continuous z-scans of confocal images, termed confocal microscopy through focusing (CMTF).
Simultaneous epithelial and stromal thickness analysis and objective assessment of corneal light backscattering were obtained from digital image analysis of the CMTF scans. Corneal reinnervation and anterior stromal keratocyte density and wound healing morphologic features were evaluated on high resolution, in vivo confocal images. Manifest refraction was measured and corneal clarity was graded by slit-lamp biomicroscopy.
Epithelial thickness averaged 45+/-10 microm at 1 month, 50+/-8 microm at 3 months, and 52+/-6 microm at 12 months after PRK, as compared with 51+/-4 microm before surgery, demonstrating complete restoration of the preoperative thickness without compensatory hyperplasia. Interestingly, epithelial rethickening had no significant correlation with refractive regression. By contrast, stromal regrowth (from 1-12 months) averaged 6+/-12 microm (range, 27 microm thinning-22 microm rethickening) and correlated closely (r = 0.84, P<0.001) with changes in refraction that averaged 0.84+/-1.23 D, ranging from -1.63 D (hyperopic shift) to +3.38 D (myopic regression). Stromal rethickening increased proportionally with the actual photoablation depth (r = 0.63, P<0.01); linear regression analysis suggested an average regrowth rate of 8% per year for the entire study group. Stromal rethickening was not associated with CMTF haze development over time, suggesting that haze and regression were caused by two independent wound healing mechanisms. In agreement with these findings, all "hazy" corneas showed increased numbers of anterior stromal wound healing keratocytes with increased reflectivity of both nuclei and cell bodies, suggesting that cellular-based reflections, as opposed to extracellular matrix deposition, are the major origin of increased corneal light scattering after PRK.
Taken together, these data indicate that keratocyte-mediated regrowth of the photoablated stroma appears to be the main cause of myopic regression in humans treated with a 6-mm diameter PRK, whereas hyperopic shifts appear to be a direct consequence of stromal thinning. By contrast, the corneal epithelium appeared to restore its preoperative thickness without contributing significantly to the refractive changes after PRK. Finally, this study also provides strong evidence that the development of haze after PRK is directly associated with increased cellular reflectivity from high numbers of wound healing keratocytes.
评估准分子激光原位角膜磨镶术（PRK）后导致屈光不稳定和角膜 haze 形成的机制。
前瞻性、非随机、对照病例系列研究，自身对照。
纳入 17 例低度至中度近视（-2.88 至 -9.13 屈光度[D]）患者的 17 只眼。
手术干预采用标准化的直径 6mm 的 PRK 手术，使用 Meditec MEL 60 准分子激光（德国赫罗尔德斯贝格的 Aesculap-Meditec 公司）。在手术前以及 PRK 术后 1、3、6、9 和 12 个月，使用共聚焦图像的快速连续 z 扫描（即通过聚焦的共聚焦显微镜检查[CMTF]）评估光凝中心。
通过 CMTF 扫描的数字图像分析，同时获得上皮和基质厚度分析以及角膜光背散射的客观评估。在高分辨率的活体共聚焦图像上评估角膜再神经支配、前基质角膜细胞密度和伤口愈合形态特征。测量明显屈光不正，并通过裂隙灯生物显微镜检查对角膜清晰度进行分级。
PRK 术后 1 个月上皮厚度平均为 45±10μm，3 个月时为 50±8μm，12 个月时为 52±6μm，而手术前为 51±4μm，表明术前厚度完全恢复且无代偿性增生。有趣的是，上皮再增厚与屈光回退无显著相关性。相比之下，基质再生（1 - 12 个月）平均为 6±12μm（范围为 27μm 变薄至 22μm 再增厚），且与平均为 0.84±1.23D 的屈光变化密切相关（r = 0.84，P<0.001），屈光变化范围为 -1.63D（远视偏移）至 +3.38D（近视回退）。基质再增厚与实际光凝深度成比例增加（r = 0.63，P<0.01）；线性回归分析表明整个研究组的平均年再生率为 8%。随着时间推移，基质再增厚与 CMTF haze 形成无关，这表明 haze 和回退是由两种独立的伤口愈合机制引起的。与这些发现一致，所有“有 haze”的角膜均显示前基质伤口愈合角膜细胞数量增加，细胞核和细胞体的反射率均增加，这表明与细胞外基质沉积相反，基于细胞的反射是 PRK 后角膜光散射增加的主要来源。
综上所述，这些数据表明，在接受直径 6mm 的 PRK 治疗的人类中，角膜细胞介导的光凝基质再生似乎是近视回退的主要原因，而远视偏移似乎是基质变薄的直接后果。相比之下，角膜上皮似乎恢复到术前厚度，且对 PRK 后的屈光变化无显著影响。最后，本研究还提供了有力证据，表明 PRK 后 haze 的形成与大量伤口愈合角膜细胞的细胞反射率增加直接相关。
