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Minimally Invasive Ophthalmic Surgery

Bearbeitet von Howard Fine I, Daniel Mojon

1st Edition. 2009. Buch. xiv, 241 S. ISBN 978 3 642 02601 0 Format (B x L): 19,3 x 26 cm Gewicht: 756 g

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2.1 Conjunctival Surgery cicatricial pemphigoid, Stevens-Johnson syndrome, and fi ltering surgery have been excluded as they involve different surgical concepts. The ocular surface is composed of both the and , which constitute a unit of the mucosal epi- thelial layer with subepithelial fi brous tissues. As the area of the conjunctiva is 7Ð8 times larger than that of 2.2 the cornea, even a minor involvement of a conjunctival disease can greatly affect the ocular surface and cor- 2.2.1 Background of the Disease neal integrity. The same holds true for ocular surface surgery, as any damage to the conjunctiva can easily Conjunctivochalasis (CCh) [1] is a very common ocu- produce tissue fi brosis, thus resulting in symblepharon lar surface disorder that is generally seen among and sustained conjunctival infl ammation. Therefore, it elderly people. According to Meller and Tseng, CCh is essential that there be a minimal amount of manipu- is defi ned as redundant, loose, nonedematous con- lation of the conjunctiva when performing conjunctival junctiva between the and which tends surgery, and in cases where extensive conjunctival sur- to be bilateral and prevalent in older patients [2]. gery must be performed, proper additional treatments Pathologically, the breakdown of elastic fi bers in the that include the use of mitomycin C (MMC) and/or redundant conjunctival tissue was seen in all exam- amniotic membrane transplantation (AMT) must be ined cases without any infl ammatory cell infi ltrates [3, combined with the primary surgery to minimize sub- 4]. Lymphangiectasia was found to be associated with epithelial fi brosis. Postoperative medical treatments this disease in more than 80% of the cases [3], although using the topical application of steroids and/or sys- the other theories emphasize the association of infl am- temic administration of steroids and immunosuppre- mation with this disease [5, 6]. In our recent in vivo sives are also effective in controlling the scarring study, however, we confi rmed the breakdown of sub- events. conjunctival tissue and lymphangiectasia by using In this chapter, several conjunctival surgeries which optical coherence tomography (Fig. 2.1). incorporate the concept of minimally invasive surgery, Although common, CCh is a very unique disease in such as those for conjunctivochalasis, recurrent ptery- that it can become a common risk factor for eyes with gium, limbal dermoid, and surgery, are as well as for dry eyes [7], because redundant summarized. However, specifi c extensive conjuncti- conjunctiva is likely to distribute at the lower tear menis- val surgeries for scarred-stage chemical injury, ocular cus and may inhibit the meniscus tear fl ow, thus leading to a dysfunction of the lower tear meniscus. This dys- function can cause delayed tear clearance in dry eye S. Kinoshita () which leads to the exacerbation of dry eye-associated Department of , Kyoto Prefectural University infl ammation. On the other hand, CCh-related blockage of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto 602-0841, Japan of the meniscus can cause exacerbation of epiphora e-mail: [email protected] symptoms in an eye with lacrimal duct stenosis.

I. H. Fine, D. Mojon (eds.), Minimally Invasive Ophthalmic Surgery, 23 DOI: 10.1007/978-3-642-02602-7_2, © Springer-Verlag Berlin Heidelberg 2010 24 S. Kinoshita et al.

Before determining the symptom for surgery, it is important to examine the eye with a slit-lamp biomi- croscope under forced blinking because some CCh is hidden under the lower eyelid. In such cases, however, forced blinking may exert friction on the cornea which results in superfi cial punctate keratopathy. When CCh is accompanied by dry eye, which may be diagnosed based on an abnormal Schirmer I test value and/or short fl uorescein breakup time in addition to the super- fi cial punctate keratopathy, surgery should be consid- ered, if the case cannot be managed with eye-drop treatment alone and due to the fact that the accompa- nying CCh is prominent.

* * * * 2.2.3 Basic Concept of Surgery

The objectives of CCh surgery are to establish the lower tear meniscus from the lateral canthus to the punctum, and make the surface of the conjunctiva as smooth as Fig. 2.1 In vivo imaging of prominent conjunctivochalasis possible, to restore the tear meniscus function and reduce which appears in a case after grafting using anterior optical mechanical friction between the redundant conjunctiva coherence tomography (Visanteª). Breakdown of subconjuncti- val connective tissues as well as presumed lymphangiectasia can and the ocular surface [4]. Many surgical methods have be observed (asterisk) been reported, such as a crescent resection, resection combined with inferior peritomy and radial relaxing inci- In addition to tear meniscus dysfunction, redundant sion, and excision with AMT and scleral fi xation [2, 8]. conjunctiva may cause precorneal tear fi lm instability However, these methods involve no fi rm concept for tear adjacent to the redundant conjunctiva and mechanical meniscus reconstruction and most of the procedures tar- friction may be exerted between the redundant conjunc- get only the redundant conjunctiva inferior to the cornea, tiva and the ocular surface, especially in cases of dry while redundant conjunctiva in the nasal and temporal eye. In cases of CCh accompanied by dry eye, dry eye- areas are ignored, although all those procedures can pro- related corneal damage and the patients’ symptoms may vide an effective reduction in the extent of CCh. be worsened via the CCh-related mechanisms com- Especially in eyes with epiphora, complete establishment pared to dry eye alone. of the lower tear meniscus from the lateral canthus to the punctum is required to restore the meniscus route for the lacrimal drainage pathway. Therefore, the ideal surgical method must include a surgical step for the treatment of 2.2.2 Indication for Surgery redundant conjunctiva in the nasal and temporal areas, and the reconstruction of the entire lower tear meniscus The most important point to be noted is that surgery as well as the elimination of ocular surface undulations for CCh is considered only for cases with symptoms. should be achieved in any variations of CCh. An asymptomatic case, even if there is prominently redundant conjunctiva distributed along the meniscus, is not an indication for surgery. Cases with irritation, 2.2.4 Surgical Procedure epiphora, and recurrent subconjunctival hemorrhage are the appropriate indications for surgery when those (Figs. 2.2 and 2.3) symptoms can be explained by tear meniscus dys- function and/or the mechanical action of redundant To completely reconstruct the lower tear meniscus and conjunctiva. totally smooth the conjunctival surface (Fig. 2.4), the 2 Minimally Invasive Conjunctival Surgery 25

Fig. 2.2 The lower part of the conjunctiva with redundancy is fi rst marked by the use of a newly developed chalasis marker (1) and then divided into 3 blocks (2, 3, 4; areas shown in red). The redundant conjunctiva is then resected according to the amount of redundancy within each block. Resection of a semilunar conjunctival fold (4) and minor adjustment of conjunctival redundancy around the temporal (6) and/ or nasal part of the conjunc- tiva for more precise smoothing of the conjunctival surface are added if necessary. Stitches are also shown (from 3 to 6)

lower half of the bulbar conjunctiva, where CCh is pre- 4. Subconjunctival fi brous tissues are excised distal to dominantly distributed, is divided into three blocks. the arc-like incision to easily stretch the lax con- The redundant conjunctiva within each block is then junctiva and obtain a fi rm attachment of the con- independently resected depending on the redundancy junctiva to the episclera. within the block. The surgical procedure for simple 5. Radial incisions are made with the chalasis scissors CCh is comprised of the following steps: in the lax conjunctiva to create three conjunctival blocks distal to the arc-like incision. 1. Topical anesthetic eye drops including 2% oxibu- 6. The conjunctiva in the lower block is pulled upward procaine and epinephrine are instilled. and redundant conjunctival tissue that can be over- 2. Planned incision lines are made using a newly devel- laid on the limbal conjunctiva is then resected and oped marker (Chalasis Marker M-1405; Inami Co., sutured using approximately fi ve 9Ð0 silk stitches. Ltd., Tokyo, Japan); for small eyes, forced bilateral eye 7. For treating lateral blocks, resection of redundant movement is necessary to obtain appropriate marking. temporal and nasal conjunctiva is performed, with 3. Subconjunctival anesthesia is performed using 2% the eye being positioned in a contra-lateral direc- lidocaine, followed by making an arc-like incision tion to avoid postoperative wound breakage due to to the anesthesia-ballooned conjunctiva using newly postoperative eye movement, and then tightly developed scissors (Chalasis Scissors M-1406; sutured with 9Ð0 silk stitches. Inami Co., Ltd.) along the line created by the marker 8. Plica semilunaris is subsequently resected when it at the lower half of the bulbar conjunctiva. is encountered and is left un-sutured. 26 S. Kinoshita et al.

Fig. 2.3 Surgical steps of 12 operation for conjunctivocha- lasis at the time of operation. Operational steps correspond to those shown in Fig. 2.2

3 4

5 6

2.2.5 Postoperative Follow-Up drops used before the surgery. Early postoperative complications may include secondary lymphangiecta- sia, disconnection of operative wound sutures, and pyo- Postoperatively, patients are advised to wear an eye genic granuloma due to a reaction to the 9Ð0 silk suture. patch for a period of 1 week to prevent any conjuncti- The secondary lymphangiectasia can be managed by val breaks while sleeping; sutures are removed 2 weeks needling or excision, and pyogenic granuloma can be after the operation. During the fi rst two postoperative managed with topical steroids or surgical removal. weeks, 0.1% betamethazone sodium phosphate and 0.3% levofl oxacin are instilled 4 times daily; after the removal of stitches, 0.1% fl uorometholone is instilled instead of betamethazone 4 times daily, together with 2.3 0.3% levofl oxacin twice daily. Instillation times for the 0.1% fl uorometholone are reduced according to the 2.3.1 Background of the Disease extent of postoperative infl ammation and are then dis- continued within 2 months after the operation. and the Concept of Minimally In dry eye patients, preservative-free artifi cial Invasive Surgery are instilled 7 times daily in addition to the postopera- tive eye drops, and are then replaced within 2 months Pterygium is a common ocular surface disorder with after the surgery with the same combination of eye clinical features involving chronic injection of 2 Minimally Invasive Conjunctival Surgery 27

Fig. 2.4 Panoramic picture of representative sample case with seen in the interpalpebral zone and the operation resulted in conjunctivochalasis without dry eye (upper: before operation; complete reconstruction of the tear meniscus lower: 3 months after operation). No redundant conjunctiva is conjunctiva and slow invasion of conjunctiva beyond the clinical features is also crucial for the prevention of the limbus onto the cornea. The prevalence rate of pri- recurrence. A minimally invasive and safe surgical mary pterygium ranges between 0.7 and 31% in vari- modality is the key for reducing prolonged postopera- ous regions around the world [9]. Early pterygium and tive infl ammation, one of the risk factors that greatly , a common type of conjunctival degenera- affects the prognosis. In addition to the various adjunc- tion, are generally not problematic, except cosmeti- tive measures such as treatment with MMC, AMT cally, and therefore should not be considered for minimizes recurrence and postoperative complications. surgery. However, severe progression or recurrence of Also, AMT appears to promote early conjunctival epi- pterygium sometimes leads to clinical problems such thelial wound healing. The current trend of performing as corneal scarring and irregular . Advanced a sutureless conjunctiva graft or AMT using fi brin glue scarring may extend close to the optical zone and contributes to the minimally invasive surgical concept. , resulting in visual loss and restric- This type of surgical modality results in a secured graft tion of ocular mobility, respectively. Therefore, deter- attachment with minimal infl ammation and shortens mination of the appropriate time point for surgical surgical time. Many current reports have demonstrated treatment is essential for the prevention of visual dys- the advantage of using fi brin gel for improving the function. Choice of the correct surgical procedure to fi t clinical success of pterygium removal, as it provides 28 S. Kinoshita et al. for a minimally invasive surgery and results in less 2.3.4 Surgical Procedures chance of recurrence of the disease. Previously, simple resection with bare scleral closure was used for cases of early or small pterygia. Although 2.3.2 Indication for Surgery this surgery is the most noninvasive procedure, a vari- ety of studies have shown a high rate of recurrence associated with this technique when not accompanied There are numerous reports that explore the surgical by adjunctive therapy. treatment of pterygium, yet medical treatment such as It is now widely accepted that adjunctive therapy anti-infl ammatory medications should be tried before and the creation of a physical barrier such as limbal resorting to surgery [10]. Although the main objectives transplantation dramatically reduce the risk of recur- of surgical treatment are apparent, the indication and rence. The adjunctive intraoperative application of timing for surgery are not clearly defi ned. The most MMC has been commonly used and is found to important point of pterygium surgery is to excise the improve the prognosis [11Ð14]. MMC suppresses the pterygium and inhibit recurrence of the disease. proliferation of conjunctival fi broblasts, which appear Reoperation requires substantially more invasive sur- to be responsible for the etiology and recurrence of gery, reduces the chances for a successful prognosis, pterygium. The safe concentration and the time of and increases the risk of complications. The appropri- MMC treatment range between 0.02 and 0.04% for ate minimum area of resection and minimally invasive 3Ð5 min. The intraoperative application of MMC is surgical procedure should be selected on the basis of relatively safe; however, excessive use of MMC has a clinical features (e.g., chronic injection, bilateral ptery- risk of invasive damage to both the cornea and . gium, and thickening of the Tenon’s tissue). Postoperative complications such as scleromalacia and persistent epithelial defects have resulted from over- invasive surgery [15, 16]. Therefore, from the point of minimally invasive surgery, it is important that MMC 2.3.3 Basic Concept of Surgery is not applied to surgically damaged or thin sclera and that the application period is minimized. The purpose of surgery in primary pterygium is to Conjunctival rotational fl aps and conjunctival trans- remove hyperproliferating subconjunctival tissue and plantation are commonly used surgical methods to pre- the abnormal pterygium head, thus minimizing the vent recurrence [17]. Although both procedures are risk of recurrence. Attention should be focused on: (1) invasive forms of surgery that damage the healthy minimizing the area of excision; (2) the use of intraop- region of the conjunctiva, these ectopical conjunctival erative chemicals; (3) technique or innovative usage of grafts result in fast epithelial closure and provide a new adhesives for wound closure; and (4) transplantation barrier against pterygium invasion. Transplantation of of tissue to the area of excision to promote epithelial a free conjunctival graft is especially useful for cases healing and inhibit recurrence. The size of the resec- of recurrent pterygia, where a large epithelial defect tion and prompt wound healing are fundamental issues may result from resection. Clinical trials have also for minimizing surgical invasion, especially in primary demonstrated that conjunctival grafts secured with cases. fi brin gel are not only as stable as those secured with In advanced and recurrent pterygium, to prevent fur- sutures, but also reduce infl ammation signifi cantly ther recurrences and/or reconstruct surgically induced [18Ð20]. Amniotic membrane (AM) is now widely conjunctival cicatrization, additional concepts have been accepted as an effective biological tool to inhibit ptery- proposed. These include: (1) reconstruction of the lim- gium recurrence (Fig. 2.5), as it promotes epithelial bal barrier to block pterygium reinvasion and (2) recon- wound healing and prevents infl ammation. AMT struction of the conjunctival area lost by excessive appears to successfully improve the prognosis of surgical resection and scarring. For the treatment of severely recurrent pterygium by minimizing surgically advanced or recurrent cases, these factors must take pre- induced invasion. Freeze-dried AM can also be used cedence over the concept of noninvasive surgery. for this purpose [21, 22]. 2 Minimally Invasive Conjunctival Surgery 29

Fig. 2.5 Pterygium surgery with MMC and AMT. (1) Head part space for 1Ð5 min; (4) MMC is rinsed by the excess sodium of pterygium is removed from the cornea; (2) fi brovascular tis- saline solution; (5) amniotic membrane and (6) conjunctiva are sue in subconjunctival space is removed; (3) 0.04% MMC sutured onto the bare sclera absorbed in microsponges is applied under the conjunctival

2.3.5 A Biologic Adhesive for Sutureless 2.3.6 Postoperative Follow-Up Pterygium Surgery Minimally invasive surgery reduces the risk of intraop- A biologic adhesive such as fi brin glue (or Tisseel) is a erative and postoperative complications, including new surgical tool that provides an alternative to sutures damage to the medial rectus. Suffi cient caution should for conjunctival grafts and AM transplantation. The therefore be paid during the removal of subconjuncti- tissue glue consists of a biological two-component val tissue, especially in cases of recurrent pterygia. sealant. Lyophilized fi brinogen is reconstituted in Major postoperative complications associated with aprotinin solution to provide the fi rst component, and pterygium surgery include infection, corneal ulcers, lymphilized thrombin is reconstituted in calcium chlo- and scleromalacia. Scleromalacia is the least desirable ride to provide the second component. The use of fi brin complication due to the fact that it can reappear even gel provides a noninvasive surgical response compared after years of MMC treatment. Therefore, the mini- to a suture procedure. Koranyi et al. [19] reported a mum amount of MMC should be applied to prevent pterygium recurrence rate of 5.3% with glue versus recurrence. 13.5% with sutures. Early reduction of infl ammation Although the precise pathogenesis of pterygium is and adherence of the graft may contribute to the reduc- unclear, postoperative infl ammation is associated with tion of immunoresponse. The short surgical time also the recurrence of pterygium. Therefore, a minimally contributes to the minimal-invasiveness of the surgery. invasive surgery reduces infl ammation and the cicatriz- Thus, our group has been seeking to create a new type ing response that is crucial for the prevention of fi bro- of biologic adhesive made entirely of plant-based blast activity. The combination of minimally invasive materials [23]. surgery with adjunctive therapy is essential to prevent 30 S. Kinoshita et al. pterygium recurrence. Current nonsuture techniques cornea. A donor cornea of the same size is then placed using fi brin gel successfully reduce surgically induced in that area and fi xed with 10Ð12 interrupted 10Ð0 infl ammation and shorten surgical time. nylon sutures. If the dermoid is large, the conjunctiva is treated with 0.04% MMC for 3 min. It is preferable to remove the conjunctival dermoid at the same time. 2.4 Limbal and Conjuntival Dermoids However, a conjunctival dermoid that has penetrated deeply into the upper-temporal sclera should be left as it is and should not be excised extensively, to avoid 2.4.1 Background of the Disease severe postoperative complications. Cosmetic recov- ery is easily achieved. A limbal dermoid is a congenital disorder, seen mostly at the lower-temporal limbus, and its size becomes slowly larger in proportion to the size of the cornea. It 2.4.4 Postoperative Follow-Up is often associated with a conjunctival dermoid at the temporal area, the size and thickness of which vary in each patient. It can cause both cosmetic abnormality After keratoplasty, topical antibiotics (e.g., 0.3% ofl ox- and decreased visual acuity by causing astigmatism. acin eye drops four times daily) and corticosteroids An amblyopic eye must be treated properly by visual (e.g., 0.1% dexamethasone or 0.1% fl uorometholone rehabilitation, such as the wearing of an eye patch or drops four times daily) are applied for approximately corrective eye glasses as removal of the limbal der- 6 months. Intraocular pressure should be checked regu- moid itself does not change the best corrected visual larly as children often suffer from steroid-induced glau- acuity. In addition, preoperative penalization treatment coma. Systemic steroids are not usually necessary for improves the postoperative visual acuity. children. Penalization treatment is not usually effective after surgery, and sutures are usually removed during the initial six postoperative months. 2.4.2 Basic Concept of Surgery 2.5 Strabismus Surgery (Fig. 2.7) To remove limbal dermoid tissue completely and to prevent the occurrence of after sur- gery, peripheral tectonic lamellar keratoplasty over the Debate can surround the question of the incision size of limbus and its adjacent conjunctiva is preferable. Both the conjunctiva in strabismus surgery. It can be proposed fresh and preserved donor may be used for this that a wider incision, and thus a wider fi eld of operation, surgery. Limbal dermoids that receive a simple resec- must be made to perform a safe and secure surgery. tion frequently develop pseudopterygium due to adja- Conversely, it can be argued that a smaller/narrower cent conjunctival over-proliferation on the residual incision will result in minimizing the amount of con- dermoid tissue in the cornea. Furthermore, a simple junctival damage, thus resulting in rapid cosmetic, resection cannot remove all the dermoid tissue from recovery, with white conjunctiva that is good in appear- the cornea due to corneal thinning. Patients usually ance. In fact, it has been found that careful management undergo the operation when they are 4Ð6-years-old of the outer eye muscles through a small incision can be due to the ease of postoperative care at that age. satisfactorily performed once a physician gains adequate experience with this type of surgery.

2.4.3 Surgical Procedure (Fig. 2.6) 2.6 Conclusion First, a minimal conjunctival resection is performed before lamellar keratoplasty. Then, the dermoid is In general, a surgery tends to evolve in the direction of marked by a trephine of appropriate size, and the becoming less and less invasive. The same holds true lamellar dissection is performed from the central for ophthalmic surgery. The purpose of performing 2 Minimally Invasive Conjunctival Surgery 31

Fig. 2.6 Surgical steps of 12 operation for limbal dermoid. Preoperative limbal dermoid (1) is marked with a slightly over-sized trephine (2), dis- sect out a limbal dermoid and a diseased peripheral cornea with one-half thickness from a central cornea (3), through an adjacent sclera (4). A lamellar cornea graft of the same size is created from a donor cornea (5), placed on the keratecto- mized bed (6), and sutured 3 4 with 10Ð0 nylon interrupted sutures (7). Postoperative manifestation (8)

5 6

7 8

minimally invasive surgery is to avoid excessive post- after surgery. One such approach is the use of a small operative wound healing, especially in areas with incision. The other approach is the use of AM, MMC fi brovascular overgrowth. As the conjunctiva is a soft, treatment, and the postoperative use of immunosup- delicate tissue, surgeons must avoid using invasive sur- pressives that presumably suppress the TGF-beta sig- gical modalities that promote excessive wound healing naling pathway and infl ammatory cytokine release. 32 S. Kinoshita et al.

9. Detels R, Dhir SP (1967) Pterygium: a geographic survey. Arch Ophthalmol 78:485 10. Hirst LW (2003) The treatment of pterygium. Surv Oph- thalmol 48:145Ð180 11. Cano-Parra J, Diaz-Llopis M, Maldonado MJ et al (1995) Prospective trial of intraoperative mitomycin C in the treat- ment of primary pterygium. Br J Ophthalmol 79:439Ð441 12. Cardillo JA, Alves MR, Ambrosio LE, Poterio MB et al (1995) Single intraoperative application versus postopera- tive mitomycin C eye drops in pterygium surgery. Ophthalmology 102:1949Ð1952 13. Chen PP, Ariyasu RG, Kaza V et al (1995) A randomized trial comparing mitomycin C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol 120: 151Ð160 14. Frucht-Pery J, Siganos CS, Ilsar M (1996) Intraoperative application of topical mitomycin C for pterygium surgery. Fig. 2.7 Small incision made at the bulbar conjunctiva is seen at Ophthalmology 103:674Ð677 strabismus surgery 15. Dunn JP, Seamone CD, Ostler HB et al (1991) Development of scleral ulceration and calcifi cation after pterygium excision and mitomycin therapy. Am J Ophthalmol 112: 343Ð344 16. Dougherty PJ, Hardten DR, Lindstrom RL (1996) References Corneoscleral melt after pterygium surgery using a single intraoperative application of mitomycin-C. Cornea 15: 537Ð540 1. Hughes WL (1942) Conjunctivochalasis. Am J Ophthalmol 17. McCommbes JA, Hirst LW, Isbell GP (1994) Sliding con- 25:48Ð51 junctival fl ap for the treatment of primary pterygium. 2. Meller D, Tseng SC (1998) Conjunctivochalasis: literature Ophthalmology 101:169Ð173 review and possible pathophysiology. Surv Ophthalmol 18. Uy HS, Reyes JM, Flores JD, Lim-Bon-Siong R (2005) 43:225Ð232 Comparison of fi brin glue and sutures for attaching conjunc- 3. Watanabe A, Yokoi N, Kinoshita S et al (2004) Clinico- tival sutografts after pterygium excision. Ophthalmology pathologic study of conjunctivochalasis. Cornea 23: 294Ð298 112:667Ð671 4. Yokoi N, Komuro A, Nishii M et al (2005) Clinical impact of 19. Koranyi G, Seregard S, Kopp ED (2004) The cut-and-paste: conjunctivochalasis on the ocular surface. Cornea 24: S24ÐS31 a no suture, small incision approach to pterygium surgery. 5. Li DQ, Meller D, Liu Y et al (2000) Tseng SC: overexpres- Br J Ophthalmol 88:911Ð914 sion of MMP-1 and MMP-3 by cultured conjunctivochalasis 20. Marticorena J, Rodriguez-Ares MT, Tourino R et al (2006) fi broblasts. Invest Ophthalmol Vis Sci 41:404Ð410 Pterygium surgery: conjunctival autograft using a fi brin 6. Meller D, Li DQ, Tseng SC (2000) Regulation of collage- adhesive. Cornea 25:34Ð36 nase, stromelysin, and gelatinase B in human conjunctival 21. Nakamura T, Inatomi T, Sekiyama E et al (2006) Novel and conjunctivochalasis fi broblasts by interleukin-1beta and Clinical application of sterilized, freeze-dried amniotic tumor necrosis factor-alpha. Invest Ophthalmol Vis Sci membrane to treat patients with pterygium. Acta Ophthalmol 41:2922Ð2929 Scand 84(3):401Ð405 7. Höh H, Schirra F, Kienecker C et al (1995) Lidparallele kon- 22. Sekiyama E, Nakamura T, Kurihara E et al (2007) Novel junctivale Falten (LIPCOF) sind ein sicheres diagnostisches sutureless transplantation of bioadhesive-coated freeze-dried Zeichen des trockenen Auges [Lid-parallel conjunctival amniotic membrane for ocular surface reconstruction. IOVS folds are a sure diagnostice sign of dry eye]. Ophthalmologe 48:1528Ð1534 92:802Ð808 23. Takaoka M, Nakamura T, Sugai H et al (2008) Sutureless 8. Otaka I, Kyu N (2000) A new surgical technique for amniotic membrane transplantation for ocular surface recon- management of conjunctivochalasis. Am J Ophthalmol 129: struction with a chemically defi ned bioadhesive. Biomaterials 385Ð387 29:2923Ð2931