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 Post subject: Corneal cell loss persists at 5 years after LASIK and PRK
PostPosted: Sun Aug 19, 2007 7:07 pm 
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Am J Ophthalmol. 2006 May;141(5):799-809. Epub 2006 Mar 20.

Corneal keratocyte deficits after photorefractive keratectomy and laser in situ keratomileusis.

Erie JC, Patel SV, McLaren JW, Hodge DO, Bourne WM.
Department of Ophthalmology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. erie.jay@mayo.edu

PURPOSE: To measure changes in keratocyte density up to five years after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).

DESIGN: Prospective, nonrandomized clinical trial.

METHODS: Eighteen eyes of 12 patients received PRK to correct a mean refractive error of -3.73 +/- 1.30 diopters, and 17 eyes of 11 patients received LASIK to correct a mean refractive error of -6.56 +/- 2.44 diopters. Corneas were examined by using confocal microscopy before and six months, one year, two years, three years, and five years after the procedures. Keratocyte densities were determined in five stromal layers in PRK patients and in six stromal layers in LASIK patients. Differences between preoperative and postoperative cell densities were compared by using paired t tests with Bonferroni correction for five comparisons.

RESULTS: After PRK, keratocyte density in the anterior stroma decreased by 40%, 42%, 45%, and 47% at six months, two years, three years, and five years, respectively (P < .001). At five years, keratocyte density decreased by 20% to 24% in the posterior stroma (P < .05). After LASIK, keratocyte density in the stromal flap decreased by 22% at six months (P < .02) and 37% at five years (P < .001). Keratocyte density in the anterior retroablation zone decreased by 18% (P < .001) at one year and 42% (P < .001) at five years. At five years, keratocyte density decreased by 19% to 22% (P < .05) in the posterior stroma.

CONCLUSIONS: Keratocyte density decreases for at least five years in the anterior stroma after PRK and in the stromal flap and the retroablation zone after LASIK.

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PostPosted: Sat Aug 25, 2007 12:44 pm 
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From the full text:

Quote:
Human corneal keratocytes remodel structural proteins to maintain homeostasis, mediate wound repair, migrate in response to injury, and die, through apoptosis, in response to wounding.


Quote:
Our current data demonstrate that this early keratocyte loss in the anterior and posterior stromal flap and in the anterior retroablation zone progresses to deficits of 32%, 42%, and 42% of pretreatment densities, respectively (P < .005), by 5 years after LASIK.


Quote:
In histopathologic studies,4,7 epithelial and stromal injuries induced by the microkeratome caused keratocyte apoptosis in the stromal layers anterior and posterior to the lamellar interface. This localized loss has been attributed to epithelial debris, including apoptosis-inducing cytokines, being tracked into the interface by the microkeratome blade.7 Recently, implanted epithelial cells (both viable cells and degenerating cells) have been found in the LASIKinterface years after surgery.9,10 These implanted epithelial cells may contribute to the localized long-term keratocyte deficits through release of apoptotic cytokines that diffuse along the interface and into the central stroma.

Alternatively, a causal relationship between decreased keratocyte density and decreased innervation after LASIK has been hypothesized.11–13,22 Müller and coworkers23 documented direct innervation of keratocytes by stromal nerves. A normal stromal keratocyte population may depend on a normal density of corneal nerves. Transplanted corneas, for example, have both keratocyte24 and nerve deficits.22 We recently showed that subbasal nerves were still reduced 21% by 5 years after LASIK,


Quote:
The clinical significance of a reduced keratocyte population after PRK and LASIK and its effect on the long-term health of the cornea is unknown. Wilson and coworkers7 suggested that the high density of keratocytes in the anterior stroma provides some form of protection against infection of the corneal epithelium and minimizes posterior extension of infections.


Quote:
The possibility of a long-term effect of keratocyte insufficiency cannot be ruled out, however, given the many functions of these cells.


PEER DISCUSSION

Quote:
DR ROGER F. STEINERT.
A frequently cited figure, from another study by Dr Bourne and coworkers, is that keratocyte density declines [naturally] by about 4% per decade.[snip]

The authors are to be congratulated for observations that are notable and, if confirmed and extended, raise concerns that excimer laser ablation may ultimately lead to a decline in keratocytes below the level necessary to maintain extracellular matrix turnover. One can speculate that this loss might lead to corneal ectasia.

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 Post subject:
PostPosted: Sat Aug 25, 2007 1:48 pm 
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Posted by kaleyedoscope in another thread:


http://www.ophthalmologytimes.com/ophth ... ?id=405941

R. Doyle Stulting MD:

"Ectasia is estimated to occur in one of every 2,500 patients undergoing LASIK, Dr. Stulting said, "but this may be an overestimate because of current exclusion criteria. It also may be an underestimate because of limited follow-up."

Reported cases of ectasia have been diagnosed up to 4 years after LASIK, he added, also noting a case of ectasia that required corneal transplantation 13 years after PRK.

"Pathology in this case suggests cell loss and abnormalities of keratocytes, leading us to wonder whether defective keratocyte metabolism could make ectasia more likely and to wonder whether mitomycin C might increase the long-term risk of ectasia," Dr. Stulting said."

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PostPosted: Sun Aug 26, 2007 6:01 pm 
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J Refract Surg. 2005 Sep-Oct;21(5):433-45.
Cohesive tensile strength of human LASIK wounds with histologic, ultrastructural, and clinical correlations.
Schmack I, Dawson DG, McCarey BE, Waring GO 3rd, Grossniklaus HE, Edelhauser HF.

Quote:
The corneal stroma is composed predominantly of a framework of insoluble collagen fibrils, water-soluble proteoglycans, and keratocytes. The collagen fibrils function primarily to maintain the shape and strength
of the tissue by resisting tensile (expansile) forces. Proteoglycans serve primarily as space fillers that resist compressive forces as this is where the incompressible water resides.10 Keratocytes form an organized syncytium and primarily serve to maintain the extracellular matrix of collagen fibrils and proteoglycan; these cells also have another role under certain conditions: they can differentiate into a tensile stress-resisting contractile cell, the myofibroblast.11

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PostPosted: Sun Jan 06, 2008 4:04 pm 
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Curr Opin Ophthalmol. 2006 Aug;17(4):380-8.

How has confocal microscopy helped us in refractive surgery?

Kaufman SC, Kaufman HE.
Henry Ford Health System: Ophthalmology, Troy, Michigan 48083, USA. svkman@yahoo.com

PURPOSE OF REVIEW: To summarize the known uses of in-vivo confocal microscopy in refractive surgery, highlighting the current developments in the field.

RECENT FINDINGS: Examination of the cornea after laser in-situ keratomileusis demonstrated that the keratocyte density within the laser in-situ keratomileusis flap and anterior residual corneal bed continued to decline during the entire 3-year period of the study. The progressive loss of keratocytes in the flap and anterior portion of the residual corneal bed could have long-term implications in terms of corneal stability, refractive stability and cellular integrity after laser in-situ keratomileusis. Additional studies showed that the density of sub-basal nerves decreased by 90% 1 month after laser in-situ keratomileusis. At some point between 3 and 6 months after laser in-situ keratomileusis, the sub-basal nerves began to recover and by 2 years they had reached approximately 50% of their original preoperative density. Analysis of sub-basal nerve density after photorefractive keratectomy reported that the nerve density completely recovered to preoperative levels by 2 years. Other confocal microscopic studies demonstrated that the microscope can detect infectious organisms in vivo, without stains or dyes.

SUMMARY: The confocal microscope is a unique diagnostic instrument that can be used to evaluate corneal healing, long-term stability and to assess complications after refractive surgery. The ability of the device to view in-vivo cellular detail, microorganisms, inflammatory cells, epitheliod cells, fibrosis and measure the postoperative thickness of the residual corneal bed after laser in-situ keratomileusis, in a noninvasive manner, highlights the unique capabilities of this instrument.

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 Post subject:
PostPosted: Sat Mar 22, 2008 3:32 pm 
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Ophthalmology. 2004 Jul;111(7):1356-61.

Long-term keratocyte deficits in the corneal stroma after LASIK.

Erie JC, Nau CB, McLaren JW, Hodge DO, Bourne WM.
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA. eric.jay@mayo.edu

PURPOSE: To determine changes in keratocyte density up to 3 years after LASIK.

DESIGN: Prospective, nonrandomized, comparative trial.

PARTICIPANTS: Seventeen eyes of 11 patients received LASIK with a planned 180-microm flap to correct refractive errors between -2.0 diopters (D) and -11.0 D (mean, -6.56+/-2.44).

METHODS: Corneas were examined by using confocal microscopy before LASIK and 1, 3, 6, 12, 24, and 36 months after LASIK. Bright objects that resembled keratocyte nuclei were manually counted by a masked observer. Cell densities were determined in anterior and posterior halves of the stromal flap, anterior and posterior halves of the 100-microm-thick layer immediately behind the ablation (retroablation layer), and the posterior third of the stroma. The region of stroma that was ablated (as measured 1 month after LASIK) was omitted from preoperative analysis. Cell densities after LASIK were compared (using1-factor repeated-measures analysis of variance) with densities in the corresponding layer of the normal preoperative stroma (which served as its own control).

MAIN OUTCOME MEASURE: Corneal keratocyte density.

RESULTS: Before LASIK, keratocyte densities in the anterior and posterior stromal flap and the anterior retroablation layer were 34 818+/-5108 cells/mm(3) (mean +/- SD), 25 390+/-4045 cells/mm(3), and 21 328+/-2980 cells/mm(3), respectively, and densities in these layers decreased 14% to 20% at 1 month after LASIK (P<0.001). Keratocyte densities in these layers remained stable at 3 and 6 months, and then gradually decreased further (P<0.001) to 26% to 36% below pre-LASIK densities by 3 years. Keratocyte densities in the remaining stromal layers did not change after LASIK.

CONCLUSION: Keratocyte densities in the stromal flap and in the anterior retroablation layer decrease during the first 6 months after LASIK and then decrease further during the next 2.5 years. Further studies on these patients and others are warranted to confirm these findings and learn their significance.

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 Post subject:
PostPosted: Sat Mar 22, 2008 5:03 pm 
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Cataract & Refractive Surgery Today
June, 2007

http://www.crstoday.com/Pages/News.php

Keratocytes' Density Remains Low After Refractive Surgery

According to a paper presented this month at the 6th International Congress on Advanced Surface Ablation and SBK, keratocytes' density decreases substantially in the anterior stroma of refractive surgery patients during the first postoperative year and remains low for several years.1

William M. Bourne, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, performed confocal microscopy on 34 eyes of 23 patients who underwent PRK or LASIK. At 7 years postoperatively, the density of keratocytes in the anterior stroma of PRK patients had dropped from 45,000 to 33,000 cells/mm², a total decrease of approximately 28%. He found a similar decrease (29%) in LASIK patients, whose keratocytes' density dropped from approximately 49,000 cells/mm² preoperatively to approximately 35,000 cells/mm² at 7 years postoperatively.

Because keratocytes secrete the collagen and proteoglycan necessary for the long-term maintenance of corneal clarity and curvature, the loss of these cells after refractive surgery may have long-term consequences for patients' corneal health, said Dr. Bourne. "We feel this possibility is unlikely, but cannot be ruled out," he added.

1. Bourne WM. The effect of PRK and LASIK on corneal keratocytes. Paper presented at: The 6th International Congress on Advanced Surface Ablation and SBK; May 5, 2007; Fort Lauderdale, FL.

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 Post subject:
PostPosted: Wed Apr 23, 2008 10:36 am 
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PTT

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 Post subject:
PostPosted: Thu May 14, 2009 10:54 am 
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Quote:
Mitomycin C treatment after PRK or other surface ablation procedures has been used empirically for years to block haze formation.14 Recently, animal studies have been performed to determine the mechanisms through which mitomycin C blocks the haze response. Although mitomycin C augments the normal apoptosis response that occurs after epithelial scrape performed during PRK,15,16 Netto et al16 demonstrated that the most notable effect is in the inhibition of mitosis of cells that function to repopulate the anterior stroma (Fig 7). Thus, progenitor cells to myofibroblasts, in addition to keratocytes, are blocked from proliferating. The end result of this treatment is that the anterior stroma has profoundly diminished cell density lasting for more than 6 months after mitomycin C treatment.16 It has not been determined when, if ever, more normal keratocyte density is restored in the anterior stroma after mitomycin C treatment. Because keratocytes function to maintain collagen, glycosaminoglycans, and other matrix materials in the stroma, there is concern regarding the long-term effects of mitomycin C, possibly measured in decades, on corneal morphology and function.16


Marcella Q. Salomao, MD and Steven E. Wilson, MD. Corneal Molecular and Cellular Biology Update for the Refractive Surgeon. J Refract Surg. 2009 May

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 Post subject:
PostPosted: Sat Jul 04, 2009 7:37 pm 
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Cornea. 2009 Jul 1. [Epub ahead of print]

Comparison of Keratocyte Density Between Keratoconus, Post-Laser In Situ Keratomileusis Keratectasia, and Uncomplicated Post-Laser In Situ Keratomileusis Cases. A Confocal Scan Study.

Javadi MA, Kanavi MR, Mahdavi M, Yaseri M, Rabiei HM, Javadi A, Sajjadi SH.
From the *Ophthalmic Research Center, of Shahid Beheshti University (MC), Tehran, Iran; daggerDepartment of Ophthalmology, Labbafinejad Medical Center, Shaheed Beheshti Medical University, Tehran, Iran; and double daggerDepartment of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

PURPOSE:: To compare keratocyte density in corneal stromal layers in keratoconus, post-laser in situ keratomileusis (LASIK) keratectasia, uncomplicated post-LASIK cases, and normal unoperated corneas by confocal scan.

METHODS:: Thirty-one unscarred corneas from 22 patients with keratoconus, 24 clear corneas from 17 cases with post-LASIK keratectasia, 12 corneas from 7 uncomplicated post-LASIK cases, and 26 corneas from 13 normal unoperated cases were evaluated by using confocal scan. None of the cases were contact lens wearers. Keratocyte densities were determined in 3 stromal layers in each cornea and compared with densities in the corresponding layers of normal unoperated corneas. Cell densities in different corneal layers were also compared in each group.

RESULTS:: In overall, 93 eyes from 59 patients with mean age of 30 +/- 7.3 years were enrolled. There was no difference in mean keratocyte density at 3 stromal layers between keratoconic and normal unoperated corneas. In post-LASIK keratectasia, keratocyte density in the anterior and posterior stromal layers was significantly lower than that in normal unoperated group. In uncomplicated post-LASIK cases, the keratocyte density at 3 stromal layers was lower than that in normal unoperated group. No difference in keratocyte density was found between post-LASIK keratectasia and uncomplicated post-LASIK cases. Furthermore, in post-LASIK keratectasia, there was a meaningful difference in keratocyte density between the anterior and posterior and between the middle and posterior stromal layers; such a difference was not observed in the uncomplicated post-LASIK cases.

CONCLUSIONS:: Mean keratocyte density in post-LASIK keratectasia and uncomplicated post-LASIK cases was lower than that in normal unoperated group. Given the different distribution of keratocytes between the stromal layers in the 2 LASIK groups, there was a nonhomogenous distribution of keratocytes in stromal layers in post-LASIK keratectasia. A homogenous distribution of keratocytes in uncomplicated post-LASIK cases may be a factor in prevention of corneal ectasia.

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PostPosted: Tue Nov 17, 2009 12:06 pm 
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J Refract Surg. 2009 Oct;25(10 Suppl):S963-7. doi: 10.3928/1081597X-20090915-12.

Confocal microscopy of corneal stroma and endothelium after LASIK and PRK.

Amoozadeh J, Aliakbari S, Behesht-Nejad AH, Seyedian MA, Rezvan B, Hashemi H.

Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

PURPOSE: To compare with confocal microscopy the changes in stromal keratocyte density and endothelial cell count due to photorefractive keratectomy (PRK) and LASIK.

METHODS: In this prospective study, 32 eyes (16 myopic patients) were examined with the NIDEK Confoscan 3 confocal microscope before and 6 months after PRK and LASIK. The preoperative mean myopia was -2.85+/-0.99 diopters (D) (range: -1.00 to -4.00 D) in 24 eyes that underwent PRK and -2.94+/-0.96 D (range: -2.00 to -4.25 D) in 8 eyes that underwent LASIK. Keratocyte density in the anterior and posterior stroma and the endothelial cell count were measured. Statistically significant changes were assessed using the t test. P<.05 was considered statistically significant.

RESULTS: Preoperative hexagonal cell percentage in the LASIK group was 52.17+/-11.43 and 51.33+/-10.98 in the PRK group. Postoperatively, the percentages were 52.96+/-7.55 and 53.34+/-10.2, respectively. Six months postoperatively, keratocyte density changed by 367.12+/-103.35 cells/mm(2) (34.7% reduction) in the anterior stroma (P<.05) and 9.25+/-28.28 cells/mm(2) (1.31% reduction) in the posterior stroma (P>.05) for the LASIK group. In the PRK group, these values were 319.71+/-83.45 cells/mm(2) (31.13% reduction) in the anterior stroma (P<.05) and 0.17+/-38.97 cells/mm(2) (0.02% reduction) in the posterior stroma (P>.05). The changes in keratocyte densities were not statistically significant between groups (P>.05). The mean number of keratocytes decreased by 37.2% in the retroablation zone of the LASIK group (P<.05). No changes were noted in endothelial cell counts.

CONCLUSIONS: A significant decrease occurred in the number of stromal keratocytes in the anterior stroma. Despite differences in surgery, the change in keratocyte density and endothelial cell counts were similar between LASIK and PRK groups (P>.05).

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PostPosted: Mon Feb 01, 2010 1:54 pm 
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