Sheraz M. Daya and Edward J. Holland

Introduction

The ocular surface of the eye is a complex functional unit consisting of several elements that all interrelate. These include the eyelids, lubrication, conjunctiva and cornea. Homeostasis of the ocular surface is vital for the maintenance of good corneal epithelium, which in turn ensures good corneal clarity and vision. Lids provide protection to the ocular surface, as well as distribution of tears through a wiper-type action picking up tears from the lower lid meniscus and distributing this across the corneal surface. Lubrication is important in terms of content, osmolality and quantity.¹ Normal conjunctiva provides mucins from goblet cells along with cytokines and the corneal limbus has been recognized and accepted as the source of limbal stem cells for the replacement of normal corneal phenotype.^2–3

Numerous techniques to rehabilitate the ocular surface have developed over the last two decades. Rehabilitation of the ocular surface includes improving the ocular surface environment and, in particular, ensuring control of inflammation, good lubrication, lid closure and elimination of keratinization and symblephara. Restoration of the normal corneal phenotype and appropriate corneal clarity is highly dependent on a good environment.⁴ A number of transplantation techniques have been employed over the years, and many have been described with various terminology, including autologous and allograft conjunctival transplantation,^5–7 keratoepithelioplasty,⁸ homotransplantation of limbal cells,⁹ limbal transplantation,¹⁰ and autologous¹¹ and allograft limbal transplantation.^12–15 These terms are not always clear in terms of tissue source (auto- or allogeneic) and precise anatomic location. Limbal transplantation, for instance, can be conjunctival alone or corneoscleral.¹⁶ Additionally, in the last 15 years tissue engineered techniques have become more popular and include culture and expansion of presumed stem cells and transplantation back to the host or to another recipient.^17–27

Clarity of communication is necessary as is the ability to accurately compare outcomes of these innovative procedures. Holland and Schwartz, recognizing the need for common terminology, provided a rationale for common nomenclature illustrating a variety of techniques described in the literature, often using similar terminology.¹⁶ The authors proposed a classification based on: (1) anatomic source of the tissue and (2) genetic source (autologous, allogeneic and living related). Since the publication in1996, further developments have resulted in the description of more techniques, as well as new sources of tissue^28–35 along with the introduction of cell culture techniques.^36–44 In order to include all current techniques and procedures, the Cornea Society felt there was a need for an internationally agreed nomenclature. This nomenclature was established by an international group of cornea surgeons involved in ocular surface transplantation through an initial steering committee (Table 39.1) and once ratified by the Board of the Cornea Society was published in Cornea.⁴⁵ A literature search was performed to ascertain types of ocular surface rehabilitative procedures reported for which inclusion in the new nomenclature. The committee agreed to expand on the principles initially proposed by Holland and Schwartz in 1996.¹⁶ The nomenclature was based on the following criteria: (1) anatomic source of the tissue being transplanted, (2) genetic source – autologous or allogeneic and to reflect histocompatability in the latter group, whether living-related or not, and (3) cell culture techniques. Types of procedures were broadly categorized by the anatomic type, source, and whether it was tissue engineered (Box 39.1). Further categorization according to anatomic type of tissue, namely conjunctival, limbal and other mucosal grafts is listed in Table 39.2. Tissue engineered procedures are listed in Table 39.3 and classified according to anatomic source of tissue.

Anatomic Type

The principle anatomic sources of tissue for ocular surface rehabilitative procedures are either conjunctiva or limbus. The use of peritonea46–48 and rectal mucosa²⁸ as sources of cells have been described, requiring the inclusion of a third category of ‘other mucosal’ tissue. Conjunctival tissue is increasingly recognized as an important contributor to the welfare of the ocular surface and felt to be necessary in cases where there is concomitant conjunctival deficiency.⁴⁹ The provision of mucins from goblet cells, as well as cytokines, contributes to the milieu and equilibrium of the ocular surface. Conjunctival tissue is not to be confused with limbal conjunctival tissue and is confined to bulbar and forniceal conjunctiva only. There have been reports suggesting the fornix as a source of conjunctival stem cells and there may be some theoretical advantage of using fornix over bulbar conjunctiva; however, as this has not been demonstrated scientifically, the committee chose not to further classify the source of conjunctiva.⁵⁰

Limbal tissue has been demonstrated to have stem cell characteristics and can be divided into two main anatomic types, including limbal conjunctiva and keratolimbal tissue. The latter includes a combination of anterior corneal tissue and scleral tissue. Conjunctival limbal tissue is procured from either the fellow eye or a living relative. The rationale for procuring only conjunctiva and not cornea, although the former is felt to have a lower quantity of stem cells, is to preserve the donor limbus. There is an added advantage in that the graft contains bulbar conjunctival tissue as well, which is useful in cases where conjunctival deficiency may also be present.

Other mucosal tissue, including buccal,29,30 nasal,^33,34 rectal²⁸ and peritoneal^46–48 have been used to populate the palpebral conjunctiva and recreate the fornix. Autologous buccal mucosa has also been used with good success in tissue engineering techniques.^31,32,35

Source

Histocompatibility is an important parameter that influences graft success.⁷ Autologous tissue, if such a source is available, is the best source; however, it is not possible in bilateral disease. The next best source of tissue is a best-matched living relative or, at a minimum, a parent or offspring, in which case half the haplotype will be in common.^51,52 Non-related tissue can be either living or cadaveric and viability of the latter often depends on the preservation technique used.⁵³ Attempts to ensure better histocompatibility by tissue marching can be performed and a non-related living donor can be used. The source of tissue that is used (autologous, living-related or cadaveric) is included in the nomenclature for both the tissue transplantation and tissue engineered sections (see Tables 39.2 and 39.3).

Tissue Engineered Grafts

Tissue engineered grafts are a more recent and exciting addition to the armamentarium of ocular surface procedures. A number of reports have demonstrated the value of ‘ex vivo’ cell cultivation techniques.17–27,36–44 Theoretical advantages include a large volume of cells without the inclusion of highly antigenic tissue as a carrier. Additionally, the loss of antigen-presenting cells further decreases the chance of acute and chronic immune rejection.²⁶ Similar anatomic origins of tissue, as well as genetic sources (autologous, living related, non-related and cadaveric) are used in the nomenclature.

Human amniotic membrane has been used as a substrate for epithelial growth36,54 or tissue filler,^55,56 as well as a biologic dressing.^57–62 Although discussed by the steering committee, amniotic membrane was not included in the nomenclature. The importance of the use of amniotic membrane as an adjuvant in ocular surface rehabilitation is acknowledged; however, it is not included in the nomenclature, as no donor cells are contributed. In tissue engineering techniques, there have been reports of use of amniotic membrane as a substrate for growth,^{21–23,25–27,38} and others have used other substrates^24,39–43 or none at all.^35,44 The influence of the carrier or growth substrate on outcomes has yet to be determined and in time this may require inclusion in the nomenclature.

As is the case with classification systems and nomenclature, periodic review will be required to embrace new and emerging techniques, and this will be conducted by the Cornea Society as the need arises. Meanwhile, to ensure clear communication and understanding, the cornea community is encouraged to use the Cornea Society nomenclature for ocular surface rehabilitative procedures.

References