TY - JOUR
T1 - Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy
T2 - A 1-year confocal microscopic study
AU - Moller-Pedersen, Torben
AU - Cavanagh, H. Dwight
AU - Petroll, W. Matthew
AU - Jester, James V.
N1 - Funding Information:
Supported in part by Eye Bank Association of America (TMP), Danish Eye Research Foundation (TMP), Danish Association for Prevention of Eye Diseases and Blindness (TMP), Novo Nordisk Foundation Denmark (TMP), Danish Medical Research Council (TMP), Synoptik Fonden Denmark (TMP), the National Institutes of Health (grant no.: EY07348; JVJ), and Senior Scientist Awards (JVJ, HDC), Manpower Award (WMP), and an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York.
PY - 2000
Y1 - 2000
N2 - Purpose: To evaluate the mechanism(s) producing refractive instability and corneal haze development after photorefractive keratectomy (PRK). Design: Prospective, nonrandomized, comparative case series, self-controlled. Participants: Seventeen eyes of 17 patients with low- to moderate-grade myopia (-2.88 to -9.13 diopters [D]) were included. Methods: 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). Main Outcome Measures: 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. Results: Epithelial thickness averaged 45 ± 10 μm at 1 month, 50 ± 8 μm at 3 months, and 52 ± 6 μm at 12 months after PRK, as compared with 51 ± 4 μm 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 μm (range, 27 μm thinning-22 μm 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. Conclusions: 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. (C) 2000 by the American Academy of Ophthalmology.
AB - Purpose: To evaluate the mechanism(s) producing refractive instability and corneal haze development after photorefractive keratectomy (PRK). Design: Prospective, nonrandomized, comparative case series, self-controlled. Participants: Seventeen eyes of 17 patients with low- to moderate-grade myopia (-2.88 to -9.13 diopters [D]) were included. Methods: 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). Main Outcome Measures: 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. Results: Epithelial thickness averaged 45 ± 10 μm at 1 month, 50 ± 8 μm at 3 months, and 52 ± 6 μm at 12 months after PRK, as compared with 51 ± 4 μm 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 μm (range, 27 μm thinning-22 μm 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. Conclusions: 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. (C) 2000 by the American Academy of Ophthalmology.
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U2 - 10.1016/S0161-6420(00)00142-1
DO - 10.1016/S0161-6420(00)00142-1
M3 - Article
C2 - 10889092
AN - SCOPUS:0033756170
SN - 0161-6420
VL - 107
SP - 1235
EP - 1245
JO - Ophthalmology
JF - Ophthalmology
IS - 7
ER -