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Year : 2013  |  Volume : 1  |  Issue : 1  |  Page : 64-69

Amniotic membrane transplantation in ocular surface disorders: A review

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

Date of Web Publication22-Jan-2013

Correspondence Address:
Rajesh Sinha
S-7, R. P. Centre, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

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Amniotic membrane (AM) was first used as a biomaterial in ophthalmic surgery in 1938. It was applied as a conjunctival replacement following symblepharon release. The durability, pliability and versatility of AM make it a useful adjunctive treatment in various ophthalmic procedures. This review aims to highlight the new developments, mechanisms of action, and established indications of amniotic membrane transplantation (AMT) that have been published in the last few years.

Keywords: Amniotic membrane transplantation, ocular surface disorder, chemical injury

How to cite this article:
Sinha R, Tinwala SI, Shekhar H, Titiyal JS. Amniotic membrane transplantation in ocular surface disorders: A review. J Clin Ophthalmol Res 2013;1:64-9

How to cite this URL:
Sinha R, Tinwala SI, Shekhar H, Titiyal JS. Amniotic membrane transplantation in ocular surface disorders: A review. J Clin Ophthalmol Res [serial online] 2013 [cited 2023 Mar 24];1:64-9. Available from: https://www.jcor.in/text.asp?2013/1/1/64/106293

  Chemical and Thermal Injury Top

Basu et al. (Am J Ophthalmol. 2012;153(4):643-50) evaluated 50 patients with unilateral limbal stem cell deficiency following ocular surface burns following failure of primary surgery. The resulting cultured epithelial monolayer and amniotic membrane were transplanted onto the patient's affected eye. At a mean follow-up of 2.3 ± 1.4 years, 33/50 (66%) recipient eyes maintained a completely epithelialized, avascular, and clinically stable corneal surface. A 2-line improvement in visual acuity was seen in 76% of recipient eyes. It was concluded that repeat autologous cultivated limbal epithelial transplantation successfully restores corneal epithelial stability and improves vision in eyes with recurrence of limbal stem cell deficiency, following failed primary surgery for ocular burns, without adversely affecting donor eyes.

Clare et al. (Cochrane Database Syst Rev. 2012; 12:9) conducted a review of randomized trials of medical therapy and AMT applied in the first seven days after an ocular surface burn compared to medical therapy alone. Sixty eight patients were included (32 severe, 36 moderate burns) in the study. In the moderate category, 13/20 control eyes and 14/16 treatment eyes had complete epithelialization by 21 days (p = 0.09). In the severe category, 1/17 treatment and 1/15 control eyes were epithelialized by day 21 (p = 0.93). The authors concluded that evidence supporting the treatment of acute ocular surface burns with AMT is lacking.

Liu et al. (Mol Vis. 2012; 18: 2137-46) studied the inflammation, cell traps and apoptosis inducing roles of the amniotic membrane after AMT in patients with acute chemical burns. AMT was performed within one week in 30 patients of acute chemical injury. The number of infiltrating cells in patients with severe burns was significantly higher than in patients with moderate burns or in control patients (p <0.05). The authors concluded that neutrophils and macrophages were the main cells that had infiltrated into the amniotic membrane during the acute phase of healing from a chemical burns. AMT can trap different inflammatory cells and induce apoptosis of inflammatory cells in acute ocular chemical burns.

Thanikachalam et al. (J Indian Med Assoc. 2011 Aug;109(8):586-7) reported a case of acute ocular burn in a child with calcium hydroxide with opaque cornea and limbalischaemia of more than 270° which was treated by AMT on 6 th day following injury. Postoperatively the ocular surface remained stable with no inflammation, or infection. AM restored conjunctival surface much earlier than corneal surface and prevented symblepharon formation.

Liang et al. (J Burn Care Res. 2012;33(2):32-8) evaluated 39 eyes receiving suture less AM patch with a modified symblepharon ring, and 36 eyes with conventional sutured AM patch as control. Both the operation time and the time to epithelial closure in the sutureless group were much shorter than that in the suture group (p < 0.01). The rate of re-epithelialization in the suture less group was higher than in the suture group (p < 0.05). The rate of the vascularization and symblepharon were lower in the suture less group than in the suture group (p < 0.05). This modified method is simple, minimally invasive, free from trauma, and very effective.

Tandon et al. (Br J Ophthalmol. 2011;95(2):199-204) evaluated the role of AMT in 100 patients with acute ocular burns (moderate burns n = 50, severe burns n = 50). They found that AMT promotes faster healing of epithelial defect in patients with moderate grade burns (p = 0.0004). There was no definite long-term advantage of AMT over medical therapy and mechanical release of adhesions in terms of final visual outcome, appearance of symblepharon and corneal vascularisation when compared in a controlled clinical setting.

Canturk et al. (J Pediatr Ophthalmol Strabismus 2010;47) evaluated the outcome of corneal surface reconstruction with conjunctival limbal autograft and AMT in two children with unilateral ocular chemical burn. Visual acuity improved from counting fingers at face to 20/60 in one patient and from counting fingers at 30 cm to 20/100 in the other. When used in combination with AM, conjunctival autograft allows correction of cicatricial abnormalities and early restoration of corneal surface integrity. Intervention within 6 months is desirable for rehabilitation of vision in the amblyogenic period.

Ricardo et al. (Arq Bras Oftalmol. 2009;72(2):215-20) retrospectively reviewed the records of ten eyes, submitted to AMT for treatment of ocular chemical burns (n = 6) and  Stevens-Johnson syndrome More Details (n = 4) in the acute phase. Epithelial defect healed at an average of 27.8 ± 4.7 days. The results suggested that AMT can be carried out as an additive procedure in serious cases of ocular chemical burn and Stevens-Johnson syndrome for promoting epithelialization and abolishing the inflammation and its consequences.

Kheirkhah et al. (Arch Ophthalmol. 2008;126(8):1059-66) retrospectively reviewed 5 eyes of 5 patients with grades I to III acute alkaline burns, receiving ProKera insertion within 8 days of injury to evaluate the clinical outcome of a new sutureless approach for a temporary AM patch (ProKera; Bio-Tissue, Inc, Miami, Florida). ProKera was inserted within a mean of 3.7 days after burn and repeated 1 to 3 times for 3 cases. Conjunctival defects re-epithelialized in 8.2 days, while limbal and corneal defects healed in 13.6 days. This sutureless application of an AM patch allows for early delivery of its biologic actions, which may help preserve remaining limbal stem cells and prevent late cicatricial complications in eyes with mild and moderate burns.

Miliudin et al. (Vestn Oftalmol. 2007;123(3):13-7) investigated efficiency of a silicone-dried Flexamer AM in surgical treatment of ocular burn injury in 76 patients. Excising necrotic tissues and covering of a silicone-dried Flexamer AM, performed not later than 14 days after burn injury are needed for regeneration of the epithelial surface of the eyeball and in diminishing the poor outcomes of treatment for sequels of ocular burn injury.

Tejwani et al. (Cornea 2007;26(1):21-6) retrospectively reviewed 72 eyes with thermal and chemical injuries (acute n = 24, chronic n = 48). Overall success rate was 87.5% in acute cases and 72.9% in chronic cases. Indication-wise success rates were 94.3% for epithelial defect healing, 88.2% for symptomatic relief, 59.7% for ocular surface reconstruction, and 55% for improving limbal stem cell function. Success was not achieved in any outcome measure in 1/24 (4.2%) in acute group and 6/48 (12.5%) in chronic group. They concluded that AMT can be considered as an effective modality for ocular surface restoration in chemical and thermal injuries in selected cases. Success rates in acute and chronic cases are comparable.

Tissue Engineering of Limbal Epithelium using Amniotic Membrane

et al. (Cornea 2012 May 10 [Epub ahead of print]) reported outcomes of transplantation of autologous conjunctival epithelial cells cultivated ex vivo (EVCAU) on denuded human amniotic membrane graft (AMG) in patients with total limbal stem cell deficiency (LSCD). Cultivated conjunctival epithelium formed 4 to 5 layers with the formation of basement membrane like structures. The improvement of the clinical parameters for this treatment was 10 of 12 eyes (83.3%). Corneal buttons showed a well-formed epithelium with 5 to 6 layers.

Eberwein et al. (Ophthalmology 2012;119(5):930-7) reported results of allogenic central penetrating limbo-keratoplasty in conjunction with conjunctivoplasty, mitomycin C (MMC), and AMT in patients with bilateral limbal stem cell deficiency (LSCD) in 20 eyes. The mean visual acuity (VA) increased from 0.029 (~20/400) before surgery to 0.281 (20/70) after surgery. Healthy corneal epithelium showing survival of limbal stem cells was observed in 14 eyes (70%) during complete follow-up of 36 months.

Sangwan et al. (Br J Ophthalmol. 2012;96(7):931-4) described 6 patients with unilateral and total LSCD following ocular surface burns. A 2 × 2 mm strip of donor limbal tissue was obtained from the healthy eye and divided into eight to ten small pieces which were distributed evenly over an amniotic membrane placed on the cornea. After surgery, a completely epithelialized, avascular and stable corneal surface was seen in all recipient eyes by 6 weeks, and visual acuity improved from worse than 20/200 in all recipient eyes before surgery to 20/60 or better in four (66.6%) eyes, while none of the donor eyes developed any complications.

Covre et al. (Arq Bras Oftalmol. 2011;74(2):114-7) evaluated the efficacy and ultra-structural aspects of human limbal epithelial cells cultured on AM with and without epithelium. Epithelial cultures grew over all but one denuded AM. In the group of amniotic membrane with epithelium, epithelial cell growing was observed only in one. Thus removal of AM epithelium seemed to be an important step for establishing limbal epithelial cell culture on AM.

Pauklin et al. (Dev Ophthalmol. 2010;45:57-70) investigated the clinical outcome of ocular surface reconstruction in LSCD using limbal epithelial cells expanded on AM in 40 eyes. The corneal surface could be reconstructed to full stability in 68% and clear central cornea was achieved in 84% eyes. Autologous transplantation was significantly more successful than allogeneic transplantation (76.7 vs. 50%, p < 0.05). The corneal surface could be successfully restored in 83.3% eyes with partial LSCD and in 63.3% eyes with total LSCD. VA increased significantly after both autologous (p < 0.0001) and allogeneic transplantation (p < 0.005).

Diaz-Valle et al. (Arch Soc Esp Oftalmol. 2007;82(12):769-72) reported sectoral conjunctival epitheliectomy and AMT for partial LSCD secondary to chemical injury. At 3 weeks there was an intact, smooth and stable corneal epithelium.

Park et al. (Cont Lens Anterior Eye. 2008;31(2):73-80) investigated efficacy of AMT in the treatment of various ocular surface diseases. The success rate in the patients with neurotrophic ulcer, inflammatory corneal ulcer, scleral ulcer and bullous keratopathy were 93.3%, 66.7%, 92.9% and 100%, respectively. A conjunctival autograft with AMT showed a 100% success rate without recurrence. The pain relief interval in the cryo-preserved and freeze-dried AM group was 17.7 and 23.3 days and the re-epithelialization interval was 29 and 22 days, respectively, the difference being insignificant.

Symblepharon Management

Kheirkhah et al.
(Cornea 2012 Jun 25. [Epub ahead of print]) evaluated a combined approach of cicatrix lysis, MMC application, oral mucosal transplantation (OMT), and sutureless AMT in severe symblepharon in 32 eyes. The anatomical outcome included complete success (restoration of an anatomically deep fornix) in 84.4%, partial success (focal recurrence of scar) in 9.4%, and failure (return of symblepharon) in 6.2%. No motility restriction was noted in any eye.

Goyal et al. (Arch Ophthalmol. 2006;124(10):1435-40) retrospectively reviewed 5 eyes (epidermolysis bullosa n = 2, laryngo-onychocutaneous syndrome n = 1, measles-related keratitis positive for human immunodeficiency virus n = 1) of children who underwent superficial keratectomy, symblepharon lysis, and forniceal reconstruction using amniotic membrane transplantation for symblepharon and massive pannus. The mean visual acuity pre-operatively was 1.1 log MAR and postoperatively was 0.7. Visual acuity improved in 3 eyes.

  Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Ocular Cicatricial Pemphigoid Top

Gregory et al. (Ophthalmology 2011;118(5):908-14) described outcomes in 10 consecutive patients with severe ocular surface and eyelid inflammation treated with AMT during the acute phase of SJS or TEN. Cryopreserved AM was applied to the eyelids and ocular surface of each patient during the first 10 days of illness. Repeat AMT was performed every 10-14 days as long as severe ocular surface inflammation and epithelial sloughing persisted. All patients had best-corrected visual acuity of ≥20/30, with 9 of the 10 seeing 20/20. Overall ocular surface and eyelid scarring was mild to moderate in all patients.

Shay et al. (Cornea 2010;29(3):359-61) described the efficacy and limitation of ProKera, a suture less medical device containing AM, inserted in both eyes at day 10 after onset of ocular symptoms of TEN in a 5-year-old boy. At 9-month follow-up, insertion of ProKera resulted in complete reepithelialization, clear corneas, and vision of 20/20 in both eyes. However, because of the limited area covered, ProKera may not prevent cicatricial complications in the fornix, tarsus, and eyelid margin as effectively as sutured AMT.

Shammas et al. (Am J Ophthalmol. 2010;149(2):203-213) treated 16 eyes of 8 patients with acute, biopsy-proven SJS or TEN and significant ophthalmic involvement with application of AM to the ocular surface and short-term use of intensive topical corticosteroid medication. Four surviving patients in whom the entire ocular surface was treated with AM retained visual acuities of 20/40 or better and an intact ocular surface. In contrast, 2 patients who were treated with only a Prokera device or unsutured AM sheets, leaving the palpebral conjunctiva and eyelid margins uncovered, developed more significant ocular surface abnormalities, and 1 developed a corneal perforation.

Shay et al. (Surv Ophthalmol. 2009;54(6):686-96) in a review on the use of AMT for the acute ocular manifestations of SJS and TEN concluded that sight threatening corneal complications can be prevented with early intervention of cryopreserved AMT. Significant dry eye problems and photophobia can also be avoided with this intervention.

Tandon et al. (JAAPOS 2007;11(6):612-3) reported good outcome of AMT in a case of TEN with severe bilateral ocular involvement.

Corneal Ulcers (Infective and Non-infective)

Muller et al
. (Klin Monbl Augen heilkd. 2009;226(8):640-4) reported initial therapy with multilayer AMG in 13 eyes with penetrating corneal ulcers. The anterior chamber was reestablished in 8 of 13 patients (62%) after an average of 5.25 days (range: 1-15).

Fuchsluger et al. (Graefes Arch Clin Exp Ophthalmol. 2007;245(7):955-64) retrospectively evaluated 137 cases of corneal ulcers divided into 3 groups: group A, patients initially having received an AMT (92 eyes eventually followed by AMT or pKP as a second intervention); group B, patients initially having received an AMT (32 eyes followed by botulinum toxin type A injection in the upper lid as a second intervention); group C, patients initially treated only by botulinum toxin type A injection (13 eyes followed occasionally by AMT or pKP or additional botulinum toxin type A injection). The total frequency of re-operations was 45.3%. In group A, the re-operation rate was 44.6%. Treating with subsequent amniotic membrane reduced re-operation rate to 30.4%. In group C, re-operation rate of 69.2% was the highest one compared with groups A and B; this rate could be drastically reduced by a following AMT to 23.1%.

Grzetic-Lenac et al. (Coll Antropol. 2011;35 Suppl 2:167-9) described 21 patients with corneal ulcer (n = 18) or non-healing epithelial defect (n = 3) unresponsive to conventional treatment. All patients were treated by AMT. Levels of all 3 investigated cytokines (IL-1 alpha, TNF alpha and VEGF) were significantly higher as compared to controls p < 0.005). Amniotic membranes that were used contained 775.69 ± 613.98 pg/mL of IL-1 alpha, 0.036 ± 0.033 pg/mL of sTNF and 175.01 ± 166.63 pg/mL of VEGF-R. Supporting effect of the AMT could be explained by the fact that AM secretes its natural anti-inflammatory antagonists.

Jain et al. (Ann Ophthalmol (Skokie) 2007;39(1):71-3) studied the role of AMT in a 40-year-old patient with the diagnosis of acne rosacea presenting with perforated peripheral corneal ulcer. Three applications of cyanoacrylate glue along with bandage contact lens failed to seal the perforation. Two months after the presentation, corneal perforation was successfully managed with AMT. The final best corrected visual acuity of 6/6 was achieved.

Bialasiewicz et al. (Ophthalmologe 2006;103(11):940-4) described AMT for noninfectious trachoma-associated corneal ulcers in 25 eyes of 17 patients with trophic corneal ulcers and symblepharon (cicatrizing trachoma: 19 eyes, SJS: 4 eyes, alkali burns: 2 eyes). Nine of 19 eyes with trachoma, 3 of 4 eyes with Stevens-Johnson syndrome, and 2 of 2 eyes with chemical burns showed complete reepithelialization and stromal recovery after 28-35 days. At 6 months post-op, 15/19 trachoma eyes (79%) compared to 2/6 non-trachoma eyes (33.3%) had developed a recurrence of symblepharon (p = 0.0592). Persistent long-term reepithelialization was observed only in 1/19 trachoma eyes (5.3%) versus 4/6 non-trachoma eyes (66.7%, p = 0.005); 3/19 trachoma eyes with a recurrence of ulcers had perforated after 6 months.

  Necrotizing Scleritis Top

Karalezli et al. (Orbit 2010;29(2):88-90) reported a case of necrotizing scleritis after pterygium surgery with conjunctival autografting (CA) and intraoperative Mitomycin C (MMC) and its treatment with AMT and systemic steroid. Over the next 2 weeks, the graft vascularization was complete and there was no complication which required further treatment.

Cordero-Coma et al. (Arch Soc Esp Oftalmol. 2009;84(11):577-80) reported a case of necrotizing sclerokeratitis after uncomplicated cataract surgery which was managed with systemic immunosuppressive agents and AMT. They concluded that conjunctival resection and AMT may be necessary to temporarily interrupt local immunologic events in severe cases. However, associated systemic immunomodulatory therapy seems to be mandatory.

Casas et al. (Cornea 2008;27(2):196-201) described the combined use of tenonplasty, lamellar corneal patch graft, and AMT in managing scleral ischemia and/or melt in 5 eyes. Surgical measures were effective to reduce or eliminate photophobia, facilitate epithelialization, halt sclera melt, and preserve the globe integrity in all eyes except for 1 eye, in which a second attempt was needed to completely correct scleral ischemia.

Pterygium Surgery

Kaufman et al.
(Ophthalmology 2012 Oct 11) conducted a review of 51 studies comparing bare sclera excision, conjunctival or limbal autograft, intraoperative mitomycin C, postoperative mitomycin C and AMT for primary and recurrent pterygia. Evidence indicates that bare sclera excision of pterygium results in a significantly higher recurrence rate than excision accompanied by use of certain adjuvants. Conjunctival or limbal autograft was superior to amniotic membrane graft surgery in reducing the rate of pterygium recurrence.

Sekeroglu et al. (Int Ophthalmol. 2011;31(6):433-8) studied the efficacy and safety of suture less AMT combined with narrow-strip conjunctival autograft using fibrin glue tissue adhesive in 30 eyes with primary pterygium. Twenty-nine patients (96.7%) had no complaints after first postoperative week and 28 (93.3%) patients had no recurrences after 1 year follow-up.

Shao et al. (Int J Ophthalmol. 2011;4(3):280-3) evaluated the efficacy and safety of a novel suture less AMT or CAT (conjunctivo-limbal autograft transplantation) using fibrin glue for primary pterygium associated with cysts in 9 patients. During a mean follow-up of 8.00 ± 0.67 months, all eyes maintained a smooth and stable corneal epithelial surface without recurrent erosion or persistent epithelial defect. The limbal donor site showed the presence of mild depressions without the formation of pseudopterygium.

Kheirkhah et al. (Cornea 2008;27(1):56-63) retrospectively studied 27 eyes of 23 patients with primary (n = 12) or recurrent (n = 15) pterygia operated by extensive removal of subconjunctival fibrovascular tissue and intraoperative application of 0.04% mitomycin C in the fornix, followed by AMT by using either fibrin glue (14 eyes) or sutures (13 eyes). For a follow-up of 29.6 ± 17.2 months, 16 (59.3%) eyes without postoperative conjunctival inflammation resulted in favorable outcomes. Conjunctival inflammation around the surgical site was noted in the remaining 11 (40.7%) eyes and was significantly more common in eyes with sutures than those with fibrin glue (61.5% vs. 21.4%, respectively; p = 0.05).

Following Excision of Mass Lesions

Verdagueret al.
(Arch Soc Esp Oftalmol. 2011;86(5):154-7) reported use of interferon alpha 2β, partial keratectomy and AMT for the treatment of a recurrent conjunctival squamous carcinoma.

Asoklis et al. (Eur J Ophthalmol. 2011;21(5):552-8) reported clinical results of patients treated by preserved human AMT following removal of conjunctival and limbal tumors in 9 patients (9 eyes). No surgical or early postoperative complications were observed. In all eyes, complete healing of the tissue defect occurred, resulting in a stable, wet, and non-inflamed epithelium.

Motolese et al. (Eur J Ophthalmol. 2010;20(3):604-7) reported a case of isolated conjunctival Bowen disease treated with surgical resection and AMT. It was seen that in the conjunctival location of the lesion, AMT is a useful therapeutic choice after surgical resection.

Zhou et al. (Yan Ke Xue Bao. 2008;24(1):39-43) compared the effect of fresh versus preserved AMT for conjunctival surface reconstruction after symblepharon lysis in 55 eyes (fresh n = 22, preserved n = 33). In 31/55 eyes (56.4%) there was resolution of eye movement restriction. In 9/55 eyes (16%) slight eye movement restriction remained. In 27.3% moderate symblepharon recurred. The effects of surgery were similar between fresh and preserved AMT (chi2 = 0.466, p = 0.797).

Carvalho-Rego et al. (Arq Bras Oftalmol. 2008;71(1):22-7) evaluated the use of human AM for ocular surface reconstruction after conjunctival squamous cell carcinoma resection in 8 eyes. In four patients (71.4%) surgical treatment was successful, with good ocular surface stability. In two patients (28.6%) there was mild cicatricial alterations.

Pirouzian et al. (J Pediatr Ophthalmol Strabismus 2012 1;49(2):114-9) evaluated the efficacy of multilayered AM for ocular surface reconstruction following removal of pediatric corneao-limbal dermoids in 3 patients. There was rapid postoperative corneal re-epithelialization, reduced postoperative pain, and diminished postoperative scarring in all patients.

Superior Limbic Keratoconjunctivitis and Conjunctivochalasis

Gris et al.
(Cornea 2010;29(9):1025-30) compared the efficacy of conjunctival resection (n = 8) versus conjunctival resection with AMG (n = 8) in patients with superior limbic kerato conjunctivitis not responsive to medical therapy in 16 eyes. After surgery, all cases undergoing conjunctival resection and 7 of 8 cases undergoing conjunctival resection with AMG remained asymptomatic. One case undergoing conjunctival resection with AMG experienced recurrence, requiring reoperation 2 years later (conjunctival resection without AMG). Despite the potential benefits of the AMG, this procedure did not provide additional advantages in this study.

Maskin et al. (Cornea 2008;27(6):644-9) evaluated the hypothesis that the therapeutic effect of AMT in symptomatic temporal conjunctivochalasis improves tear clearance in 12 eyes. AMT did not improve tear clearance; however, it significantly improved symptoms (p = 0.001), surface erosions (p = 0.008), and log MAR visual acuity (p = 0.007) and reduced artificial tear use (p = 0.015). There was also an improvement in tear strip wetting, but it was statistically insignificant.

Kheirkhah et al. (Am J Ophthalmol. 2007;144(2):311-3) evaluated the feasibility of performing suture less AMT using fibrin glue for conjunctivo-chalasis in 25 eyes. For a mean follow-up of 10.6 ± 4.3 months, all eyes achieved a smooth conjunctival surface with complete or significant improvement of symptoms in 44% and 56%, respectively. Complications included focal conjunctival inflammation in four eyes and pyogenic granuloma in one eye.

Pseudophakic Bullous Keratopathy

Gregory et al.
(Can J Ophthalmol. 2011;46(2):169-74) reported outcomes of anterior stromal micropuncture (ASP) combined with AMT in the management of painful bullous keratopathy (BK) with poor visual potential in 12 eyes. Corneal epithelial healing was complete in 11 eyes 1 month postoperatively. Pain and conjunctival inflammation resolved in 11 patients (91.67%) and improved from severe to mild in the remaining patient. AMG retention was seen in all eyes after the procedure, suggesting that ASP may improve the long-term retention rate of AM.

Chawla et al. (Eur J Ophthalmol. 2008;18(6):998-1001) reported sutureless amniotic membrane fixation using fibrin glue in two cases of symptomatic bullous keratopathy with poor visual potential. In both cases, 3 weeks later, the ocular surface had completely re-epithelialized. At 6 months follow-up, both patients were symptom free without the need for any medication.

Georgiadis et al. (Clin Experiment Ophthalmol.2008;36(2):130-5) reported the results of cryopreserved human AMT for management of symptomatic BK in 81 eyes. Seventy-one (87.6%) eyes became asymptomatic with healed epithelium, 7 required repeat AMT and 3 underwent penetrating keratoplasty. Visual acuity improved in 64 (79%) patients.

Srinivas et al. (Eur J Ophthalmol. 2007;17(1):7-10) reported pain relief in 100% of eyes with painful bullous keratopathy following AMT.

Corneal Perforation and Bleb Leaks

Chan et al.
(Cornea 2011;30(7):838-41) described the "Swiss roll" AMT in corneal perforations wherein a roll of AM was placed across the row of preplaced sutures and sutures tied to secure the membrane. An amniotic membrane patch was placed over the graft, which was protected by a bandage contact lens.

Herpetic Infections

Meller et al.
(Klin Monbl Augenheilkd. 2010;227(5):393-9) described the clinical application of AMT for the management of corneal infections with Herpes simplex and Herpes zoster virus.

Calcific Band Keratopathy

Esquenazi et al.
(Ophthalmic Surg Lasers Imaging.2008;39(5):418-21) reported a 91-year-old man with advanced glaucoma and symptomatic recurrent band keratopathy following 3 previous EDTA chelations. AMT using fibrin sealant over 8 mm area following removal of calcific band lesion was done. Wound healing was completed in 10 days and a stable ocular surface was restored without pain or inflammation and without recurrence.

Vernal Keratoconjunctivitis

Guo et al.
(Cornea 2012 Oct 18. [Epub ahead of print]) evaluated the outcome of surgical resection and AMT to cover the tarsal conjunctival defect for treatment of refractory symptomatic giant papillae in VKC in 13 eyes. There was no recurrence of giant papillae in any eye. Corneal shield ulcers and punctate epithelial erosions healed within 2 weeks and did not recur. Three patients experienced recurrence of VKC symptoms, but without giant papillae, which could be well controlled by topical medications.

  Others Top

Strabismus Surgery

Mehendale et al.
(JAAPOS 2011;15(4):404-6) reported successful use of AMT in a case of traumatic, restrictive strabismus.

Strube et al. (Ophthalmology 2011;118(6):1175-9) reported the use of AMT in 8 eyes with post-operative restrictive strabismus. All patients had failed additional standard surgery to remove the adhesions, including 1 patient treated with mitomycin C for recurrent scarring after pterygium. Reoperation using AMT was associated with improvement of ocular motility in 6 of the 7 patients; 1 patient had recurrence of scarring with persistent diplopia. The remaining 6 patients had no significant recurrence of scarring, and motility remained stable during the follow-up.


Mahdy et al.
(Cutan Ocul Toxicol. 2010;29(3):164-70) evaluated usefulness of a freeze-dried AMT (placed over the scleral flap and under the conjunctiva) with mitomycin C (MMC) in the maintenance of functioning bleb in cases of pediatric glaucoma in 15 eyes (controls not receiving AMT n = 15). The mean postoperative IOP was significantly decreased to 15 ± 1 mm Hg and 17.2 ± 2.9 mm Hg in the 2 groups, respectively. Complications such as inflammation, choroidal detachment, or toxic keratopathy were not noted in cases but were noted in controls.

Sheha et al. (J Glaucoma. 2008;17(4):303-7) compared outcomes of trabeculectomy combined with mitomycin C (MMC) and AMT with those of trabeculectomy with MMC alone in 37 eyes with refractory glaucoma. It was seen that trabeculectomy combined with MMC and AMT had higher success rates (p = 0.03), lower postoperative mean IOPs (p < 0.0001), and less encapsulated bleb formation (p = 0.02).

Contracted Socket

Kumar et al.
(Orbit 2006;25(3):195-203) compared AMT (group A, n = 10) with mucous membrane grafting (group B, n = 10) in contracted socket. There was better patient comfort and fornix and volume measurements in group A. However there was no difference regarding the rate of complications between both the groups (p = 0.29).

Surgically Induced Astigmatism

Zhou et al.
(Ophthalmologica 2006;220(6):389-92) performed photoastigmatic refractive keratectomy (PARK) on rabbits and grafted AM on the cornea. The effect of AM on the degree of astigmatism was evaluated by topography and cycloplegic refraction. AM not only eliminated PARK-induced astigmatism but prevented surgically induced astigmatism.

Radiation Plaque Therapy

Finger et al.
(Arch Ophthalmol. 2008;126(4):531-4) described use of AM as buffer between the cornea and radioactive eye plaques in 6 eyes with melanomas where (0.1-mm-thick) amniotic membrane was interposed between the metal plaque edge and the cornea. On a scale of 1 (none) to 10 (severe), all 6 patients reported pain levels of 1 with no significant effect on radiation dose.

Drug Reservoir

Resch et al.
(J Ocul Pharmacol Ther.2011;27(4):323-6) studied the drug release from pretreated AM in vitro. Significant ofloxacin reservoir capacity of a single human amniotic layer could be demonstrated in vitro. AM acted as an ofloxacin slow release device for upto 7 h in vitro, depending on the duration of pretreatment of AM. Individual pretreatment of AM could increase beneficial effects of AM transplantation, especially in infectious keratitis.

Light Initiated Bonding of Amniotic Membrane to Cornea

Verter et al.
(Invest Ophthalmol Vis Sci. 2011;52(13):9470-7) introduced a novel sutureless, light-activated technique that securely attaches amnion to cornea with strong, immediate bonding through protein-protein crosslinks in rabbit corneas. Cryopreserved human amniotic membrane, stained with Rose Bengal (RB), was placed over a full-thickness wound in deepithelialized rabbit cornea and was treated with green laser. Mechanism studied indicated that RB forms two complexes with amnion stromal collagen, the bonding requires oxygen, and that singlet oxygen mediates protein crosslinking.

Wang et al. (Lasers Surg Med. 2011;43(6):481-9) compared photochemical tissue bonding (PTB) versus traditional sutures in AMT for repair of OSD in 40 rabbit eyes. Corneal re-epithelialization did not differ significantly between the groups; however the inflammatory mediators were significantly lower in PTB group. Fewer new vessels were present in the PTB group (2.91 ± 1.00) compared to the suture group (4.33 ± 1.15) at day 28 (p < 0.05). PTB treatment led to less corneal scarring as well.

Growth Factors

Lopez-Valladares et al.
(Acta Ophthalmol. 2010;88(6):e211-6) reported that AM derived from donors with higher age and gestational age showed lower levels of growth factor, total protein, bFGF, HGF, KGF and TGF- β(1).


Das et al.
(Int Ophthalmol. 2009;29(1):49-51) reported a case of fungal keratitis following anterior stromal puncture with AMT for pseudophakic bullous keratopathy after 4 weeks. Aspergillus sp. was isolated from the corneal scraping and treated with topical and systemic anti-fungal medications.

The spectrum of clinical indications of use of AMG in ophthalmology continues to expand and encompass a varying range of ocular surface pathology. It has been shown to provide a viable alternative or option in many clinically challenging situations. It can be used as a temporary graft to promote ocular surface healing by suppressing damaging inflammation, fibrosis and neovascular growth. As a permanent graft, it can promote the healing or replacement of damaged or missing tissue by providing a substrate for normal tissue growth. Sutureless applications with fibrin glue have been aimed at making the procedure easier and more comfortable for the patient. Further research will expand clinical applications and also give us greater insight into the mechanisms of action of this unique tissue.


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