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 Post subject: Mitomycin C (MMC) research articles
PostPosted: Wed Jun 14, 2006 10:46 pm 
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J Refract Surg. 2006 May;22(5):511-3.

Dry eye after photorefractive keratectomy with adjuvant mitomycin C.

Kymionis GD, Tsiklis NS, Ginis H, Diakonis VF, Pallikaris I.

Department of Ophthalmology, Institute of Vision and Optics, University of Crete, Heraklion, Greece. kymionis@med.uoc.gr

PURPOSE: To report a patient with dry eye after bilateral photorefractive keratectomy (PRK) with mitomycin C treatment in one eye.

METHODS: A 29-year-old woman underwent PRK for moderate myopia. The left eye was randomly assigned and intraoperative topical mitomycin C was administered. The right (control) eye was treated with intraoperative corticosteroid only.

RESULTS: The patient developed dry eye symptoms and superficial punctuate keratopathy in the eye treated with mitomycin C. Fifteen months after surgery no improvement was noted.

CONCLUSIONS: Photorefractive keratectomy with mitomycin C treatment could induce or exacerbate dry eye.

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PostPosted: Fri Jun 16, 2006 2:57 pm 
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http://www.aao.org/education/sit_cornea/0019.cfm

Specialty News and Views: Cornea/External Disease - April 2006

The Specialty News and Views section represents the opinions of the contributing authors and does not imply endorsement by the American Academy of Ophthalmology. The Cornea/External Disease team members are: Donald Stone, MD; Surendra Basti, MD; Thomas Harvey, MD; Saiyid Hasan MD; and Ivan Schwab, MD.

Mitomycin C in the Aqueous Following Corneal Application

A recent animal study showed that mitomycin C (MMC) was consistently detected in the aqueous following a 2 minute application of the solution to corneas with and without an intact epithelium.1 The primary intent of Torres and colleagues was to study eyes where MMC had been applied following photorefractive keratectomy (PRK).

After applying MMC 0.02% for 2 minutes to 2 groups of hen eyes?those that had PRK and those with intact corneal epithelia?the researchers sampled aqueous humor at different time points (10, 30, 60, 360, and 720 minutes). High performance liquid chromatography detected significant quantities of MMC in both groups up to 60 minutes after application. Eyes with PRK had higher levels and could be seen up to 360 minutes later. No drug was undetectable in any eye at 12 hours.

While the presence of MMC in the aqueous following application during glaucoma filtration procedures has been documented, there has been a paucity of literature regarding aqueous levels in eyes following application to the ocular surface. This study unequivocally demonstrates that MMC remains in the aqueous in all eyes following topical application.

MMC is a potent wound healing modulator used by glaucoma, refractive, and corneal surgeons. Advocates of its use have extrapolated success of this agent in decreasing failure of filtration blebs to areas of refractive and corneal surgery. Its efficacy has led to a progressive widening of its applications in recent years. However, this antineoplastic agent can have potential long-term consequences on intraocular structures, because it blocks DNA-RNA replication and protein synthesis.

Previous studies involving topical application of MMC 0.04% at 3-4 times a day have demonstrated ocular surface toxicity on impression cytology and suggested a radiomimetic effect for at least 8 months following therapy.2,3 It is also believed that the toxic effects of MMC can be delayed and cumulative. In light of these facts, it is evident that more investigations of the pharmacokinetic and cytotoxic effects of MMC are needed, particularly with regard to aqueous levels. In the interim, it may be prudent to limit the use of this agent as well as to provide informed consent about the lack of knowledge regarding the long-term effects of MMC.

REFERENCES:

1. Torres RM, Merayo-Lloves J, Daya SM, et al. Presence of Mitomycin-C in the Anterior Chamber After Photorefractive Keratectomy. J Cataract Refract Surg. 2006;32: 67-71.

2. McKelvie PA, Daniell M. Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia. Br J Ophthalmol. 2001;85:1115-1119.

3. Dogru M, Erturk H, Shimazaki J, Tsubota K, Gul M. Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia. Cornea. 2003;22:622-639.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Fri Jun 16, 2006 3:00 pm 
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J Cataract Refract Surg. 2006 Jan;32(1):67-71.


Presence of mitomycin-C in the anterior chamber after photorefractive keratectomy.

Torres RM, Merayo-Lloves J, Daya SM, Blanco-Mezquita JT, Espinosa M, Nozal MJ, Bernal JL, Bernal J.

Instituto Universitario de Oftalmobiologia Aplicada, Universidad de Valladolid, Spain.

PURPOSE: To assess the presence of mitomycin-C (MMC) in hen aqueous humor after photorefractive keratectomy (PRK).

SETTING: Instituto Universitario de Oftalmobiologia Aplicada, Faculty of Medicine, University of Valladolid, and Department of Analytical Chemistry, Faculty of Sciences, University of Valladolid, Valladolid, Spain.

METHODS: Mitomycin-C 0.02% was applied topically for 2 minutes to a right hen's eye after PRK (Group A) and to the left eye with intact epithelium (Group B). At different time points (10, 30, 60, 360, and 720 minutes), aqueous humor was extracted and high-performance liquid chromatography was performed to detect and quantify MMC levels.

RESULTS: The mean maximum drug concentration of MMC measured in the aqueous humor was 187.250 microg/L +/- 4.349 (SD) in Group A and 93.000 +/- 4.899 microg/L in Group B, both detected 10 minutes after topical application. Statistically significant differences were found between Groups A and B at 10, 30, and 60 minutes, with decreasing MMC levels in both groups but a higher concentration in Group A. After 360 minutes, MMC levels were undetectable in Group B and after 720 minutes in Group A.

CONCLUSIONS: Mitomycin-C was detectable in the aqueous humor of the hen eye after topical application in PRK-treated eyes and in eyes with intact epithelium. The presence of MMC is of concern as it may lead to ocular toxicity in the long term.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Fri Jun 16, 2006 3:02 pm 
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Br J Ophthalmol. 2001 Sep;85(9):1115-9.


Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia.

McKelvie PA, Daniell M.

Department of Anatomical Pathology, St Vincent's Hospital, Melbourne, Victoria, Australia. mcelevpa@svhm.org.au

BACKGROUND/AIMS: Topical mitomycin C (MMC) therapy has been used for treatment of ocular surface squamous neoplasia (OSSN) since 1994. Relatively few studies have reported the cellular changes in ocular surface following MMC.

METHODS: Impression cytology was studied in four patients with ocular surface squamous neoplasia, either primary or recurrence after previous excisional biopsy. The authors studied samples obtained using Millipore filters at intervals between 4 and 17 weeks after commencement of MMC, and compared them with pretreatment cytology.

RESULTS: MMC induced changes of cytomegaly, cytoplasmic vacuolation, nucleomegaly with nuclear wrinkling, and binucleation or multinucleation were seen in some cells in all samples. However, nuclear/cytoplasmic (N/C) ratio in these enlarged cells was normal. These changes mimicked those seen following radiation therapy in uterine cervix. Changes of increased nuclear and cell size with increased N/C ratio were seen in some dysplastic cells. The predominant form of cell death was apoptosis with fewer cells showing necrosis.

CONCLUSIONS: MMC appears to produce cell death in OSSN by apoptosis and necrosis. Cellular changes related to MMC mimic those caused by radiation-cytomegaly, nucleomegaly, and vacuolation. MMC related changes may persist in ocular surface epithelium for at least 8 months following MMC therapy.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Fri Jun 16, 2006 3:04 pm 
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Cornea. 2003 Oct;22(7):627-39.


Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia.

Dogru M, Erturk H, Shimazaki J, Tsubota K, Gul M.

Uludag University, Faculty of Medicine, Department of Ophthalmology, Bursa, Turkey. muratodooru@yahoo.com

PURPOSE: To evaluate the tear function and ocular surface alterations in patients with primary CIN before and after treatment with topical mitomycin (MMC).

PATIENTS AND METHODS: We describe seven patients with unilateral CIN treated with 0.04% topical MMC three times daily until full eradication of the lesion. The patients underwent tear and ocular surface examinations including Cochet-Bonnet corneal sensitivity measurements, tear film break-up time (BUT), Schirmer test, and Rose-Bengal staining before, at the time of resolution of the CIN, and at the final follow-up. Conjunctival impression cytology was performed before treatment and at the last visit.

RESULTS: The mean pretreatment corneal sensitivity was 30.3 +/- 7.4 mm and improved to 55 +/- 5 mm at the final visit (P < 0.05). There were no aqueous-deficient eyes. The BUT values and Rose-Bengal staining scores also showed significant improvement at the last follow-up compared with the pretreatment values (P < 0.05). Initial impression cytology specimens showed goblet cell loss, higher grades of squamous metaplasia, areas of isolated keratinized, binucleated, and actively mitotic disfigured epithelial cells in all patients. The mean goblet cell density and squamous metaplasia grade were observed to improve significantly at the last visit (P < 0.05). MMC-induced cytologic changes were seen to persist long after cessation of treatment in some patients. All eyes remained free of recurrence and complications during the follow-up period.

CONCLUSION: We found 0.04% topical MMC treatment tid until full eradication to be effective in the management of CIN. The ocular surface disease of CIN was characterized by disturbance of tear film stability, goblet cell loss, and increased squamous metaplasia in all patients. Impression cytology proved useful in attaining the diagnosis of CIN, evaluating the effect of treatment, and showing MMC-related long-term changes on the ocular surface.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Fri Jun 16, 2006 3:06 pm 
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J Cataract Refract Surg. 2004 Aug;30(8):1742-50.

Early corneal edema following topical application of mitomycin-C.

Chang SW.

Department of Ophthalmology, Far Eastern Memorial Hospital, 21 ZSection 2, Nan-Ya South Road, Ban-Chiao, Taipei 220, Taiwan. swchang@mail.femh.org.tw

PURPOSE: To determine the effect of mitomycin-C (MMC) on the cornea after a single intraoperative application.

SETTING: Department of Ophthalmology, Far Eastern Memorial Hospital, Ban-Chiao, Taipei, Taiwan.

METHODS: Mechanical epithelium debridement of the central 10.0 mm of the cornea was performed in 63 pigmented rabbits. One group of corneas (MMC1, n = 42) was soaked with MMC 0.01% solution for 2 minutes; the second group (MMC2, n = 42) was soaked with MMC 0.02% solution for 2 minutes. Control corneas (n = 42) were soaked with balanced salt solution for 2 minutes. Changes in the central corneal thickness, clarity, epithelial defect size, endothelial cell density, and endothelial apoptosis in the 3 groups were examined on days 0, 1, 2, 3, 5, 7, and 14.

RESULTS: There was a dose-dependent increase in corneal thickness, decrease in corneal clarity, and increase in endothelial apoptosis after a single intraoperative application of MMC. The endothelium was significantly swollen and became pleomorphic and polymegethic with a concomitant decrease in endothelial cell density, also in a dose-dependent manner.

CONCLUSIONS: A single application of MMC on the corneal surface caused dose-dependent corneal edema and endothelial apoptosis in the rabbit model. Further clinical study of human eyes is warranted.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Fri Jun 16, 2006 3:07 pm 
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Acta Ophthalmol Scand. 1998 Feb;76(1):80-2.


Intraoperative mitomycin C and the corneal endothelium.

Sihota R, Sharma T, Agarwal HC.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi.

PURPOSE: Mitomycin-C (MMC) is a useful adjunct to high risk glaucoma surgery. No clinical data regarding the deleterious effect of mitomycin-C on the corneal endothelial cells are available.

METHODS: Thirty eyes of 28 adult patients with high risk glaucomas were randomized to three groups. Group-I underwent a trabeculectomy alone, Group II, trabeculectomy with intraoperative 0.2mg/ml MMC and Group III, trabeculectomy with intraoperative 0.4mg/ml MMC. Preoperative and 3-month postoperative corneal endothelial cell counts were analysed.

RESULTS: The percentage cell loss in Group I was 3.73+/-2.73%, in Group II 13.90+/-4.69% and in Group III 14.52+/-7.8%. Statistical analysis revealed a significant difference in cell loss between Group I and Group II and Group I and Group III, but not between Group II and Group III.

CONCLUSION: There is a significant loss of corneal endothelial cells three months after trabeculectomy with adjunctive MMC.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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 Post subject:
PostPosted: Wed Apr 04, 2007 12:30 pm 
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This one is not peer-reviewed:

http://www.osnsupersite.com/view.asp?rID=20313

OCULAR SURGERY NEWS U.S. EDITION February 1, 2007

Mitomycin-C can reduce corneal haze after laser refractive surgery

Francesco Carones, MD, explains how MMC can be used to treat or prevent haze.

By Francesco Carones, MD

Quote:
The major criticism in the use of MMC after laser refractive surgery refers to the potential side effects and complications associated with its long-term cytostatic action on tissues when applied in a topical fashion on the corneal stroma. Several researchers have reported corneoscleral melt after MMC application after pterygium excision. Also, the long-term integrity of the endothelial layer is supposed to be at risk.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Sat Aug 25, 2007 6:51 pm 
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Am J Ophthalmol. 2006 May;141(5):799-809.

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


DR STEVEN E. WILSON:

Quote:
I encourage you to use the same technology to look at patients who are having mitomycin prophylactic treatment for prevention of haze; probably 90 percent of refractive surgeons are using mitomycin without any long-term data as to the effect. It is clear the reason mitomycin works so well is that it eliminates 100 percent of all corneal cells in about 20 percent of the anterior cornea. Similar to your concerns, I think they are even magnified in those patients because data after six months in the animal model shows that none of those cells have returned. What happens in the future since we have limited experience with these types of patients? In 10 to 20 years, are we going to see anterior corneal necrosis or other problems? Your type of study could give us more data about that in humans.

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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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PostPosted: Sat Aug 25, 2007 7:52 pm 
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Non-peer reviewed, 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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"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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 Post subject:
PostPosted: Thu Feb 21, 2008 12:14 am 
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Not peer-reviewed:

http://www.osnsupersite.com/view.asp?rID=26511
OSN SuperSite Breaking News 2/20/2008
LASEK, epi-LASIK to remain niche procedures despite some advantages, surgeon says

Excerpt:

Quote:
"This is, in my opinion, the only potential benefit of these procedures: They minimize the risk of haze without the use of mitomycin-C, which is not such an innocent drug," she said.

She strongly emphasized that the use of mitomycin-C by refractive surgeons should strictly be limited to high-risk eyes. Cases of scleral melting were found, in her personal experience, 3 to 4 years after using the drug in pterygium surgery, and the need for dilution poses further problems.

_________________
Broken Eyes

"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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 Post subject:
PostPosted: Fri Mar 14, 2008 3:34 pm 
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Not peer-reviewed:

http://www.osnsupersite.com/view.asp?rID=26809

Quote:
?This is, in my opinion, the only potential benefit of these procedures. They minimize the risk of haze without the use of mitomycin, which is not such an innocent drug,? she said.

She emphasized that the use of mitomycin-C by refractive surgeons should be limited strictly to high-risk eyes. Cases of scleral melting were found, in her personal experience, 3 or 4 years following the use of this medication in pterygium surgery, and the need for dilution poses further and not negligible problems.

_________________
Broken Eyes

"The price good men pay for indifference to public affairs is to be ruled by evil men." Plato


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