Tissue Grafts for Management of Corneal Defects

Educational Objectives

The goal of this program is to improve the treatment of corneal disease. After hearing and assimilating this program, the clinician will be better able to:

1. Elaborate on the advantages and disadvantages of techniques that use limbal stem cells cultivated ex vivo for transplantation.

2. Treat corneal defects with tissue grafts derived from preserved irradiated or dried tissues.

3. Apply tissue grafts during keratoprosthesis surgeries.

Summary

Case 1: 16-yr-old patient had right-sided corneal lesion that did not respond to topical steroids; B-scan ultrasonography revealed lesion located at limbus; posterior surface of cornea not affected

VisionGraft: γ-irradiated; available in different sizes and shapes (eg, full-thickness doughnut-shaped for use with keratoprostheses, split-thickness half-moon shapes for covering glaucoma patches); testing with sutures showed good results; tissue remained clear with no swelling; preserved in albumin with shelf life of ≈2 yr at room temperature; studies reported favorable properties and outcomes from tissue; no hypersensitivity elicited

Procedure: speaker used metal trephine to cut to ≈70% of depth of cornea; excised lesion with crescent blade; patched with half-thickness VisionGraft sterile cornea

Patient’s diagnosis: histopathologic examination of lesion biopsy revealed lymphocytes engulfed in histiocytes; pathognomonic for Rosai-Dorfman disease (histiocytosis; <10 cases reported in cornea); immunohistochemical studies positive for S100 antigen (cells ectodermally derived) and CD68 (lymphocytic marker), negative for CD1A (antigen-presenting cell marker); disease usually involves orbital area and adnexa; treatment of choice unknown; recurrence common despite various treatments; some cases regress

Outcome: graft remained clear, patient had good corrected vision 3 mo after transplantation

Case 2: 6-yr-old girl had dermoid of limbus; lesion excised and replaced with graft; outcome — graft remained fairly clear with some neovascularization at edge after months; tissue appears not to allow penetration of neovascularization

Case 3: patient with herpetic keratitis and keratouveitis developed descemetocele; had severe decrease in vision with thin cornea (≈150 µm); speaker patched area of treated bed with partial-thickness sterile cornea and sutured; outcome — vision improved; 1 yr later, graft remained clear; overall corneal haze remained from previous keratouveitis

Case 4: patient had decreased vision in one eye after SJS; examination revealed small, full-thickness hole in cornea; speaker patched with Ambio5 (tissue containing amnion and chorion, 100 µm thick); possible to use disposable or nondisposable trephines; made shallow incision and placed patch; outcome — cornea healed under patch with fibrosis; graft dislodged spontaneously and melted

Case 5: patient with severe diabetes, dry eye, proliferative vitreoretinopathy, and traction retinal detachment; underwent pars plana vitrectomy in left eye; developed nonhealing corneal ulcer and melting; speaker patched with partial-thickness VisionGraft; secured patch with interrupted nylon sutures; outcome — patient did well postoperatively but did not gain vision; graft epithelialized in <1 wk

Keratoprosthesis surgeries

Case 1: procedure — speaker used precut VisionGraft tissue (8.5-mm outer diameter, 3.0-mm inner diameter); not necessary to trephine donor cornea; handled tissue with forceps; no concerns about endothelial layer; anterior and posterior plates of device clamped together before transplantation; procedure rapid; after placing posterior plate on top of VisionGraft tissue, locking ring snapped into place; precut tissue — in keratoprosthesis, severely eccentric central trephination of donor cornea possible (causes difficulty in suturing and with vision after surgery because of alignment problems with optics of device and fovea); also, because cut not totally straight, outer diameter possibly >3.0 mm, leading to postoperative leaks; issues eliminated by precut tissue

Case 2: patient with Sjogren syndrome had severe melt; posterior plate of keratoprosthesis exposed; speaker repaired prosthesis with Ambio5 cut into doughnut shape, placed under anterior plate around stem; used 3 layers (≈400 µm); outcome — patient did well and retained keratoprosthesis for 3 yr

Case 3: patient with TEN (similar to SJS but with >30% of body involved and higher mortality [≈30% vs ≤5% for SJS]); if epithelial loss occurs in cornea or conjunctiva, speaker recommends using amniotic membrane from fornix to fornix and reflected onto tarsal conjunctiva to prevent formation of symblepharon and ankyloblepharon; possible to use AmbioDry2 or fresh-frozen amniotic membrane; speaker tucks at fornices and places separate grafts on undersurface of superior and inferior tarsal conjunctiva; prevents acute complications; outcome — patient had no symblepharon but scarring of tarsal conjunctiva evident; not possible to maintain tear film without fornices

Case 4: 3-yr-old girl with frequent, spontaneous corneal perforations; corneal neovascularization seen in both eyes with central thinning and opacity; eyelid margins had no meibomian gland orifices; patient had loss of hair and staphylococcal infections in other mucosa; cleft palate and ectrodactyly of feet and hands indicated EEC syndrome; such patients born without sebaceous or meibomian glands, and may have limbal stem cell problems; patients develop corneal opacity, perforations, and lose eyes; usually colonized with Staphylococcus aureus; treatment — speaker used ProKera ring (lamellar graft would not become moistened by tear film and could melt); ProKera ring also helpful for patients with burns or SJS who cannot tolerate surgery; ring has 2 layers with fresh-frozen amniotic membrane clamped inside; outer diameter 16 mm (some fornices required to maintain it); possible to use with nonhealing epithelial defects or in setting of infectious keratitis instead of bandage contact lens

Readings

Akpek EK et al: The use of precut, γ-irradiated corneal lenticules in Boston type 1 keratoprosthesis implantation. Am J Ophthalmol 154::495, 2012; Burcu A et al: Surgical rehabilitation following ocular chemical injury. Cutan Ocul Toxicol 33:42, 2014; Chu HS et al: Anterior corneal buttons from DSAEK donor tissue can be stored in Optisol GS for later use in tectonic lamellar patch grafting. Cornea Mar 26, 2014; Daoud YJ et al: The intraoperative impression and postoperative outcomes of gamma-irradiated corneas in corneal and glaucoma patch surgery. Cornea 30:1387, 2011; Daya SM et al: Living related conjunctival limbal allograft for the treatment of stem cell deficiency. Ophthalmology 108:126, 2001; Daya SM et al: Cornea society nomenclature for ocular surface rehabilitative procedures. Cornea 30:1115, 2011; Gomes JA et al: Corneal reconstruction with tissue-engineered cell sheets composed of human immature dental pulp stem cells. Invest Ophthalmol Vis Sci 51:1408, 2010; Liu Y et al: One man’s poison is another man’s meat: using azithromycin-induced phospholipidosis to promote ocular surface health. Toxicology 320C:1, 2014; Majo F et al: Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature 456:250, 2008; Mathews PM et al: Evaluation of ocular surface disease in patients with glaucoma. Ophthalmology 120:2241, 2013; Monteiro BG et al: Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Prolif 42:587, 2009; Sangwan VS et al: Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency. Br J Ophthalmol 96:931, 2012; Sikder S et al: Evaluation of irradiated corneas using scatterometry and light and electron microscopy. Cornea 30:503, 2011; Stevenson W et al: Gamma-irradiation reduces the allogenicity of donor corneas. Invest Ophthalmol Vis Sci 53:1751, 2012; Tan DT et al: Corneal transplantation. Lancet 379:1749, 2012; Tay E et al: Crescentric amniotic membrane grafting in keratoprosthesis-associated corneal melt. Arch Ophthalmol 128:779, 2010; Yang X et al: Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells. Mol Vis 14:1064, 2008.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Akpek is a consultant for and on the Speakers’ Bureau of Bausch & Lomb, and receives grant/research support from Alcon and Allergan. The planning committee reported nothing to disclose. In this lecture, Dr. Akpek presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Akpek spoke at the 56th Annual Postgraduate Symposium in Ophthalmology — Advances in Corneal Disease, held March 1-2, 2013, in Columbus, OH, and presented by The Ohio State University, Havener Eye Institute. To learn more about CME programs presented by The Ohio State University, please visit ccme.osu.edu. The Audio-Digest Foundation thanks Dr. Akpek and The Ohio State University, Havener Eye Institute for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP521202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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