Results of Phase III Excimer Laser Photorefractive Keratectomy for Myopia

Hersh, Peter S.; Stulting, R. Doyle; Steinert, Roger F.; Waring, George O.; Thompson, Keith P.; O'Connell, Maureen; Doney, Kimberley; Schein, Oliver D.; Michelson, Marc; Owen, John; Gordon, Mike; Wright, John R.; Brint, Stephen F.; Mead, Mariana D.; Raizman, Michael B.; Wu, Helen; Durrie, Daniel S.; Cavanaugh, Timothy; Hunkeler, John D.; Pepose, Jay S.; Galusha, J. Harley; Gold, Daniel H.; Milstein, Bernard A.

doi:10.1016/s0161-6420(97)30073-6

Cited by 136 publications

(60 citation statements)

References 50 publications

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“…For example, clinically significant corneal haze has been noted in 2-4% or more of eyes after excimer laser photorefractive keratectomy (PRK), depending on the level of attempted correction (Lipshitz et al, 1997;Hersh et al, 1997;Shah et al, 1998;Siganos et al, 1999;Kuo et al, 2004). The incidence of haze after PRK in humans increases with increasing attempted correction (Kuo et al, 2004) and increasing volume of stromal tissue removal (Moller-Pedersen et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, essentially 100% of rabbit eyes that have −9.0 diopter PRK (group VI) develop severe subepithelial opacity, whereas only 2-4% of human eyes develop severe subepithelial opacity after similar levels of PRK (Lipshitz et al, 1997;Hersh et al, 1997). However, in studies performed in human eyes enucleated to treat tumours the pattern of the wound healing response in humans is very similar to that in rabbits (Ambrósio Jr., R., et al, 2002 Early wound healing response to epithelial scrape injury in the human cornea.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, eyes that have PRK for less than six diopters of myopia rarely develop significant haze. As the level of correction increases beyond six diopters, however, the incidence of clinically significant haze increases to as high as 2-4% (Lipshitz et al, 1997;Hersh et al, 1997;Shah et al, 1998;Siganos et al, 1999). Studies of PRK in rabbits confirmed that there was also a relationship between the level of correction and haze and myofibroblast formation in this model .…”

Section: Introductionmentioning

confidence: 99%

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Stromal haze, myofibroblasts, and surface irregularity after PRK

Netto

Mohan

Sinha

et al. 2006

Experimental Eye Research

243

204

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The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze.Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups:Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery and histochemical analysis was performed on corneas for apoptosis (TUNEL assay), myofibroblast marker alpha-smooth muscle actin (SMA), and integrin α4 to delineate the epithelial basement membrane.Slit-lamp grading revealed severe haze formation in corneas in groups IV and VI, with significantly less haze in groups II, III, and VII and insignificant haze compared with the unwounded control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the approximate peak of haze formation in rabbits, revealed low myofibroblast formation in group I (1.2 ± 0.2 cells/400× field) and group V (1.8 ± 0.4), with significantly more in groups II (3.5 ± 1.8), III (6.8 ± 1.6), VII (7.9 ± 3.8), IV (12.4 ± 4.2) and VI (14.6 ± 5.1). The screened groups were significantly different from each other (p <0.05), with myofibroblast generation increasing with higher surface irregularity in the −4.5 diopter PRK groups. The −9.0 diopter PRK group VI had significantly more myofibroblast generation than the −9.0 diopter PRK with PTK-smoothing group VII (p <0.01). Areas of basement membrane disruption were demonstrated by staining corneas for integrin α4 and were prominent in corneas with grade I or higher haze. SMA-positive myofibroblasts tended to be present sub-adjacent to basement membrane defects. Late apoptosis was detected at 1 month after surgery within clusters of myofibroblasts in the sub-epithelial stroma. In conclusion, these results demonstrated a relationship between the level of corneal haze formation after PRK and the level of stromal surface irregularity. PTK-smoothing with methylcellulose was an effective method to reduce stromal surface irregularity and decreased both haze and associated myofibroblast density. We hypothesize that stromal surface irregularity after PRK for high myopia results in defective basement membrane regeneration and increased epithelium-derived TGFβ signalling to the stroma that increases myofibroblast generation. Late apoptosis appears to have a role in the disappearance of myofibroblasts and haze over time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stromal haze, myofibroblasts, and surface irregularity after PRK

Netto

Mohan

Sinha

et al. 2006

Experimental Eye Research

243

204

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“…1 Though the process of accommodation allows a number of these individuals to see normally without refractive correction, many others require spectacle, contact lens, or surgical correction, with the attendant risk of bacterial keratitis 2 or infection due to surgical correction of refractive error. [3][4][5] Additionally, children with high levels of hyperopia are at risk for accommodative esotropia, a condition that, if untreated, may result in amblyopia, impaired stereoscopic vision, and a significant reduction in vision-related functional status. 6 Although the number of children with accommodative esotropia is not well known, strabismus has been estimated to affect between 0.5% and 4% of children.…”

Section: Introductionmentioning

confidence: 99%

Familial aggregation of hyperopia in an elderly population of siblings in Salisbury, Maryland

Wojciechowski¹,

Congdon²,

Bowie³

et al. 2005

Ophthalmology

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Purpose-To determine whether hyperopia aggregates in families in an older mixed-race population.Design-Cross-sectional familial aggregation study using sibships.Methods-We recruited 759 subjects (mean age, 73.4 years) in 241 families through the population-based Salisbury Eye Evaluation study. Subjects underwent noncycloplegic refraction if best-corrected visual acuity (BCVA) was ≤20/40, had lensometry to measure their currently worn spectacles if BCVA was >20/40 with spectacles, or were considered to be plano (refraction of zero) if the BCVA was >20/40 without spectacles. Preoperative refraction from medical records was used for bilaterally pseudophakic subjects.Results-Utilizing hyperopia cutoffs from 1.00 to 2.50 diopters, age-, race-, and gender-adjusted odds ratios for hyperopia with an affected sibling ranged from 2.72 (95% confidence interval [CI], 1.84-4.01) to 4.87 (95% CI, 2.54-9.30). The odds of hyperopia increased with age until 75 years, after which they remained relatively constant. Black men were significantly less likely to be hyperopic than white men, white women, or black women.Conclusions-Hyperopia appears to be under strong genetic control in this older population.Hyeropia, or farsightedness, describes the refractive state where the focal point of light entering the eye is behind the retina, due to a short axial length relative to the eye's optical system. Hyperopia of >3.0 diopters (D) is estimated to affect 11.8 million persons over the age of 40 years in the United States, or 9.9% of the U.S. population. 1 Though the process of accommodation allows a number of these individuals to see normally without refractive correction, many others require spectacle, contact lens, or surgical correction, with the attendant risk of bacterial keratitis 2 or infection due to surgical correction of refractive error. [3][4][5] Additionally, children with high levels of hyperopia are at risk for accommodative esotropia, a condition that, if untreated, may result in amblyopia, impaired stereoscopic vision, and a significant reduction in vision-related functional status. 6 Although the number of children with accommodative esotropia is not well known, strabismus has been estimated to affect between 0.5% and 4% of children. [7][8][9][10] Esodeviations comprise >50% of this, 11 with refractive accommodative esotropia clearly playing a significant role. Evidence exists suggesting that hyperopia may be under strong genetic control. 14,15 Twin studies in England have suggested that hyperopia, treated as a binary trait, has a heritability of 89%, virtually the same as myopia. 14 Biometric traits such as axial length and radius of corneal curvature, which determine hyperopia, also demonstrated heritability in the 80% to 90% range in the British twin study. However, genetic studies of hyperopia have been far fewer than for myopia. A small number of genetic conditions have been identified that are characterized by hyperopia in conjunction with ocular 16 or systemic 17 abnormalities. To the best of our knowledge...

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“…Following this early animal research, he worked as a principal investigator in clinical trials of photorefractive keratectomy with the Summit Technology excimer laser in human eyes. 15 The data that he and others collected were presented before the U.S. Food and Drug Administration, and the device was approved in 1992. "This was the first approval for the clinical use of the excimer laser by the FDA.…”

Section: Lasikmentioning

confidence: 99%

Remembering George O. Waring, III

Randleman¹

2015

J Refract Surg

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Results of Phase III Excimer Laser Photorefractive Keratectomy for Myopia

Cited by 136 publications

References 50 publications

Stromal haze, myofibroblasts, and surface irregularity after PRK

Stromal haze, myofibroblasts, and surface irregularity after PRK

Familial aggregation of hyperopia in an elderly population of siblings in Salisbury, Maryland

Remembering George O. Waring, III

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