The Parameters to Establish a New Corneal Dystrophy

GORDON K. KLINTWORTH

ECAUSE OF THE NEED FOR A WORLDWIDE STAN- dardized

nomenclature for the corneal

dystrophies, an international committee brought together the
diverse literature on these disorders and recommended preferred names for each entity.1 Each corneal dystrophy needs
a specific name because all of these entities do not affect the same parts of the cornea or have the same method of
inheritance, pathogenesis, prognosis, or treat- ment. Like many other genetically determined diseases, knowledge
about each corneal dystrophy passes through a continuum from clinical discovery, to a clinicopathologic characterization, to
chromosomal mapping, to gene iden- tification, and to the detection of mutations. As this knowledge advances
over time, some designations gradu- ally fal by the wayside and better terms are proposed based on clinical or
clinicopathologic observations or an im- proved understanding of their cause, pathogenesis, and pathobiologic
features.2 However, attempts to provide more accurate appropriate appellations often are unsuc- cessful. After an
extended period of use, the names of some diseases become so ingrained in the literature that they are difficult to
replace. For example, retinitis pigmentosa is a prime example of a misnomer, because inflammation of the retina
(retinitis) is not a feature of this retinopathy. Nevertheless, despite attempts to replace this designation with the more
precise name of pigmentary retinopathy, the old name lives on. Even corneal dystrophy is a misnomer because entities
embraced under this umbrella do not arise from defective or faulty nutrition, as implied by the word dystrophy derived
from the Latin term dystrophia. Particu- larly for the lay public, this is probably good because changes in nomenclature are not
always easy to compre- hend. To rename diseases frequently as knowledge ad- vances may provide precision, as
hematopathologists have done with the lymphomas, but for those who are not experts in particular diseases, the
changes in nomenclature can create an aura of chaos.
At anyone point in time, all diseases are not known and new ones come to light, as occurred with the
sudden emergence of retinopathy of prematurity, AIDS, and se- vere acute respiratory syndrome. If a new corneal
disease is suspected, it is essential to determine that it has not been described previously. It is also necessary to make
sure that the condition is not a variant of a known entity. The age of the patient, the duration of signs and
symptoms, as well

as the genetic background and other factors influence the phenotypes, sometimes making it difficult or impossible to
establish a precise diagnosis on a single patient without additional information about other affected members of the
family. As learned from the corneal diseases caused by mutations in the TGFBI gene, distinct clinicopathologic entities
are not necessarily independent disorders, but may be fundamentally more similar than suspected.3
When a new or previously forgotten corneal dystrophy is described, the discoverer has the opportunity to name
the new disorder. Others encountering the same entity for the first time may be unaware of an earlier designation
and may report their observations under a different term. Thus, the names of an entity may snowball, particularly
when one of the original terms does not become established. Of all the conditions that affect the cornea, and indeed
the eye, the record number of synonyms belongs to a disorder with multiple names that include chronic actinic
keratopathy.4
Recurrent corneal erosions occur in a variety of dis- tinctly different corneal disorders, including Fuchs, lattice type
I, Meesmann, and subepithelial mucinous corneal dystrophies, as well as in other conditions. Sometimes the
recurrent erosions have an autosomal dominant method of inheritance and the erosions are the predominant feature of
the condition. Albert Franceschetti (18961968), the renowned Swiss ophthalmologist, pioneered ophthalmic
genetics and, together with 2 colleagues, published a comprehensive 2-volume book, Genetics and
Ophthalmol- ogy, in 1961.5 Buried within the first volume of this text is a large 7-generation pedigree of a
family with recurrent corneal erosions that he had published previously in 1928.6
The clinical features of affected individuals in this family originally were documented in a rudimentary way, and the
Franceschetti paper was cited by Weiss and associates under the broad umbrella of epithelial recurrent erosion dystrophy
(ERED).1 Somewhat similar cases have been named after the geographic location where the corneal dystrophy was
discovered, as in the Swedish provinces of Smland (Dystrophia Smolandiensis)7,8 and Hlsingland (Dystrophia
Helsinglanica).9,10 These variants of ERED share features with relatively minor differences, and it is debatable whether they
are indeed independent entities. Rigid geographic boundaries do not encase corneal dystro- phies, and designations
based on locations are unlikely to withstand the test of time, because the genetic pool of different mutations never
remains entirely in a single community.
Commonly a new disorder is named after the first person known to describe it, but others are labeled
after a

Accepted for publication Apr 14, 2011.

From the Duke University Medical Center, Durham, North Carolina.
Inquiries to Gordon K. Klintworth, Room 255, Medical Science
Research Building 1, Duke University Medical Center, Durham, NC
2770; e-mail: klint001@mc.duke.edu
0002-9394/$36.00
doi:10.1016/j.ajo.2011.04.010

2011 BY ELSEVIER INC.

subsequent author. The disorder with recurrent corneal erosions that was documented by Franceschetti originally was
dubbed hereditary recurrent erosion of the cornea, but it was later also referred to as Franceschetti syndrome I . Eponyms
in nomenclature are common, and many epon- ymous corneal dystrophies are named after ophthalmolo- gists: Ernst
Fuchs (18511930, Fuchs endothelial corneal dystrophy); Arthur Groenouw (18621945, Groenouw
corneal dystrophy type 1 and 2, currently known as granular corneal dystrophy and macular corneal dystrophy,
respectively); Alois Meesmann (18881969, Meesmann corneal dystrophy); Frederick W. Stocker and L.
Byerly Holt (Stocker-Holt corneal dystrophy); Max Bcklers (18951969, Reis-Bcklers corneal dystrophy); Hans-Jrgen Thiel (Thiel-Behnke corneal dystrophy); Walter F. Schnyder (18921980, Schnyder corneal dystrophy); and
Hugo Biber (18641918), Otto Haab (18501931), and Friedrich Dimmer (18551926, BiberHaab-Dimmer cor- neal dystrophy, currently called lat ice corneal dystrophy type
1), and the list goes on and on.
At one time diseases, syndromes, and anatomic structures with eponymous names were referred to in the

ALL

RIGHTS RESERVED.

155

possessive form with an apostrophe, but this practice has fallen into disrepute and the trend of not using the
possessive form has gradually gathered momentum in medical writing.11 With countless diseases having eponymous names, many individuals have difficulty learning and remembering the characteristics of the specific disorders,
but a skill in recalling them is a distinct advantage for someone interested in trivial pursuit.
The human desire to compartmentalize diseases has spawned so-called splitters and lumpers, particularly
among individuals studying genetic diseases. Those who are splitters regard each disorder with recurrent epithe- lial
erosions, such as Dystrophia Smolandiensis and Dystrophia Helsinglandica, as distinct entities, but lumpers prefer to
group all of these conditions together as variants of ERED. Although differences have been detected between
the EREDs, an understanding of the basic defects in each of them remains unknown until the actual mutations
in the responsible gene(s) have been identified. Until that time of reckoning, it wil not be known whether these
conditions are, or are not, variants of the same disease.

PUBLICATION OF THIS ARTICLE WAS SUPPORTED BY GRANTS R01EY016514, R011EY012712, AND K12 EY016333 FROM THE National Eye Institute, National Institutes of Health, Bethesda, Maryland. The author (G.K.K.) indicates no financial
conflict of interest, and is solely responsible for the content of this article.

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