Clinical trial NCT02952365
Conditions: Epithelial Ingrowth
Keywords: LASIK, Ingrowth, Tissue sealant
Sponsor: Stanford University
Start date: 2016-10-01; Completion date: 2017-05-22
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to evaluate the use of prophylactic tissue sealant to prevent epithelial ingrowth from gaining access under a LASIK flap with repeat LASIK surgery

Detailed description:
Participants will have a comprehensive eye examination once they express an interest in the study. This includes a slit lamp examination of the front of the eye and a dilated fundoscopic examination of the back of the eye. If there is any pathology noted that would exclude the participant from the study, then the participant will be informed and given an appropriate referral. If the participant is deemed appropriate for the study after a comprehensive examination included computerized videokeratography, then they can be enrolled. The participant will undergo LASIK flap lift eye surgery.

Tissue sealant will be applied at to the edge of the LASIK flap at the conclusion of the surgery. A bandage contact lens will also be placed. The bandage contact lens is used in the usual and customary fashion as in non-study LASIK flap lift surgery.

The participants will be seen on the day of surgery, post op day one, one month, and three months. The participant will receive topical antibiotics in each eye for one week following the procedure. The participant will receive pred forte 1% ophthalmic drops for one week after treatment. The participant will also receive vigamox ophthalmic drops for seven days after treatment. All of this is within the usual and customary standard of care for the treatment of participants undergoing LASIK surgery.

Arms: arm 1: Eyes undergoing LASIK enhancement will have tissue sealant applied to the eye to prevent epithelial ingrowth
Interventions: intervention 1: Tissue sealant
Intervention descriptions: intervention 1: Application of tissue sealant on eyes undergoing LASIK enhancement

Protocol documents:
Prot_SAP_000.pdf: 
NCT02952365 
 
Document Date: September 20, 2016 
 
INVESTIGATOR-INITIATED STUDY PROPOSAL 
 
A Prospective Evaluation of Tissue Sealant to Prevent Epithelial Ingrowth in Repeat LASIK Surgery 
 
  
 
The following is an investigator initiated study proposal to evaluate the relative effectiveness of  
the ReSure® Sealant at preventing epithelial ingrowth after LASIK flap re-lift.  
  
Principle Investigator:  Edward E. Manche, MD 
 
Funding:  Ocular Therapeutix, Inc. – $
 gift.  SPO pending. 
 
Introduction 
 
It is well-known that a small percentage of patients will have epithelial ingrowth after primary LASIK and 
that preoperative refractive error is a correlated factor.1 The effects of that ingrowth can be glare and 
halos; ingrowth is a significant cause of dissatisfaction after LASIK.2 The incidence of epithelial ingrowth 
is significantly higher after flap re-lift for treatment of residual refractive error.3 It has been 
hypothesized that cell migration into the flap/cornea interface postoperatively is a primary reason for 
such ingrowth.4 A sealed interface may therefore have some utility in preventing epithelial ingrowth 
after flap re-lift. 
 
The following investigator-initiated study proposal is designed to determine if a lower-than-typical rate 
of epithelial ingrowth occurs when a LASIK flap re-lift is performed and the replaced flap is sealed with 
ReSure sealant.  
 
Study specific aims:  Tissue sealant has been effectively used to prevent recurrence of epithelial 
ingrowth under the LASIK flap.  The aim of the study is to see if tissue sealant can be used to prevent 
epithelial ingrowth from occurring in the first place.  This would allow for patients to undergo LASIK flap 
lift surgery with greater safety. 
 
Unpublished data:  There is no unpublished data on the prophylactic use of tissue sealant to prevent the 
occurrence of epithelial ingrowth under the flap.  It has been used successfully to prevent recurrence of 
epithelial ingrowth under the flap. 
 
Study design and data analysis 
 
The study will be designed as a single-arm prospective trial involving 25 eyes (of up to 25 subjects) who 
are presenting for LASIK retreatment.   Sample size was calculated based on a nominal historical 
population rate of 25% ingrowth after re-lift, and an expected rate with ReSure of 5%, using an alpha of 
0.05 and a power of 0.8; with these parameters a sample of 25 eyes should be sufficient to show the 
expected difference.  
 
The study will involve 5 visits per eye, including a preoperative visit. Other visits will be the operative 
day, and 1 day, 1 week, 1 month and 3 month postoperative visits.  The primary endpoint will be 
presence of epithelial ingrowth at 1 and 3 months after the retreatment.  


NCT02952365 
 
Document Date: September 20, 2016 
Secondary endpoints will include change in refraction, best-corrected visual acuity and uncorrected 
visual acuity.  
Inclusion criteria will be those patients who are presenting for LASIK flap re-lift and re-ablation after 
initial LASIK surgery.  If a surgery occurs where there are intra-operative or immediate post-operative 
complications unrelated to the sealant the subject may be excluded from the analysis and replaced with 
an alternate. The data for that patient will be retained and the affected patient will be followed to 
monitor for adverse events, but their outcomes data would not be included in any aggregate analysis. At 
each visit subjects will be monitored for adverse events, whether related to the protocol regimen or not. 
 
Significance:  Late flap lift enhancements are associated with a higher rate of epithelial ingrowth under 
the flap margin.  Many surgeons have stopped performing late flap lift LASIK enhancements and 
switched to PRK to avoid this complication.  PRK over previous LASIK is associated with a prolonged 
visual recovery and short term ocular discomfort.  If the tissue sealant is effective at preventing or 
lowering the rate of epithelial ingrowth under the flap, then late LASIK flap lift treatments could be 
offered with greater safety.  This would benefit patients. 
 
 REFERENCES 
1. Mohamed TA, Hoffman RS, Fine IH, Packer M. Post-laser assisted in situ keratomileusis epithelial 
ingrowth and its relation to pretreatment refractive error. Cornea. 2011 May;30(5):550-2.  
2. Levinson BA, Rapuano CJ, Cohen EJ, Hammersmith KM, Ayres BD, Laibson PR. Referrals to the Wills 
Eye Institute Cornea Service after laser in situ keratomileusis: reasons for patient dissatisfaction. J 
Cataract Refract Surg. 2008 Jan;34(1):32-9. 
3. Caster AI, Friess DW, Schwendeman FJ. Incidence of epithelial ingrowth in primary and retreatment 
laser in situ keratomileusis. J Cataract Refract Surg. 2010 Jan;36(1):97-101. 
4. Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol. 2000 
Jun;129(6):746-51.    
5. Thulasi P, Kim SW, Shetty R, Randleman JB.  Recalcitrant epithelial ingrowth after SMILE treated with 
a hydrogel ocular sealant.  J Refract Surg.  2015 Dec, 31(12):847-50. 
6. Yesillimark N, Diakonis VF, Battle JF, Yoo SH.  Application of a hydrogel ocular sealant to avoid 
recurrence of epithelial ingrowth after LASIK enhancement.  J Refract Surg.  2015  Apr:31(4):275-7. 
7. He L. Manche EE.  Fibrin glue for prevention of recurrent epithelial ingrowth under a LASIK flap with 
a central buttonhole defect.  J Cataract Refract Surg.  2012 Oct;38(10):1857-60. 
8. Rojas MC, Lumba JD, Manche EE.  Treatment of epithelial ingrowth after laser in situ keratomileusis 
with mechanical debridement and flap suturing.  Arch Ophthalmol.  2004 Jul;122(7):997-1001.