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Berliner ML. Biomicroscopy of the Eye - Slit lamp microscopy of the living eye II (1949) Paul B. Hoeber, Inc. Medical Book Department Of Harper & Brothers, New York.

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This historic 1949 textbook by Berliner describes biomicroscopy of the human eye.





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LIMBAL PALISADES OF VOGT*

BY Morton F. Goldberg, MD, AND

(BY INVITATION) Anthony ]. Bron, BSC

INTRODUCTION

THE PALISADES OF VOGT WERE CLINICALLY DESCRIBED IN 1914 BY STREIFF WHO called them “radial stripes”; in 1917 by Koeppe who called them “radial pseudocysts”; and in 1934 by Graves who called them “trabeculae.”1 At one time they were thought to have a glandular function but this notion was clearly dispelled by Aurell and Kornerup in 1949.2 Because the name applied in 1921 by Vogt has persisted, we will maintain his terminology. 13*‘

The palisades of Vogt are a series of radially oriented fibrovascular ridges that are concentrated along the upper and lower corneoscleral limbus. There, they aggregate into distinct crescentic zones. They lie just peripheral to the terminal capillary loops of the limbus and just central to Schlemm’s canal. Between the connective tissue palisades are intervening radial zones of thickened conjunctival epithelium, the so-called interpalisades or epithelial rete ridges. '

The palisade and interpalisade regions thus contain specialized blood vessels and may also serve as repositories of epithelial cells. They may have clinical importance in replacing defective corneal epithelium (as for example in normal aging, recurrent corneal erosion, chemical burns, melting diseases, and delayed graft epithelialization).5'6 The morphology of the palisades and interpalisades may also explain the characteristic pattern of pigment slide and of cornea verticillata, as seen in Fabry’s disease and in drug-induced degeneration of the corneal epithelium (eg, chloroquine, amiodarone, and others).7

  • From the N ufiield Laboratory of Ophthalmology, University of Oxford, England, and from

the University of Illinois Eye and Ear Infirmary, Chicago, Ill. Supported in part by a Macy Foundation Faculty Scholar Award (Dr Goldberg), by core grant EY1792 from the National

Eye Institute, Bethesda, Maryland, and by an unrestricted research grant from Research to Prevent Blindness, Inc, New York, NY.

Tn. AM. OPHTH. Soc. vol. LXXX, 1982 156 Goldberg

Because little is known of the morphology of this region and because angiographic studies have not previously been undertaken we present the results of our biomicroscopic and angiographic investigations in both normal and abnormal human limbuses.

SUBJECTS AND METHODS

Over 40 normal adults and several additional patients with infectious conjunctivitis were examined biomicroscopically. Macrophotographs were obtained in 30 normal subjects (X 10 magnification on film) using the Brown macrocamera and the Nikon specular camera with Ektachrome 200 film. Linear measurements of the palisades and interpalisades were obtained by superimposing an enlarged photographic negative of a stage micrometer onto photographic prints of the palisade region that were enlarged identically. The micrometer (obtained from Graticules, Ltd, Tonbridge, Kent) was graduated in 0.01 mm steps.

p F luorescein angiography was performed with the Zeiss photo slit-lamp and the Zeiss 75 SL at X 16 magnification. Subjects were injected antecubitally with 5 mL of 20% sodium fluorescein, and a flash frequency at 0.5- to 1.0-second intervals and maximum power were employed.

For histologic study, the eye of an 84-year-old white woman was obtained at autopsy. The limbal tissues were fixed in formalin and stained routinely with hematoxylin and eosin. Photographs were taken with a Zeiss photomicroscope.

RESULTS

CLINICAL MORPHOLOGY

Precise focusing of the slit-lamp (Fig IA and B) and high magnification (Fig 1C) are necessary if the palisades are to be observed. They are found just peripheral to the terminal capillary loops of the limbus (Fig 2). The appearance of the palisade zone varies considerably from one individual to the next. For example it is altered by the presence of melanin (Fig 3A and B). In moderately or darkly pigmented individuals the palisades are easily seen in diffuse illumination, because they are outlined by the melanincontaining epithelial cells of the interpalisades (epithelial rete ridges). Vessels in these palisades may be obscured by dispersed pigmentation. In lightly pigmented whites the palisades may be difiicult to see in diffuse illumination, but can be observed rather well by scleral scatter. In some individuals the palisades are not visualized well at all. In many instances, Palisades of Vogt 157 158 Goldberg

FIGURE 2 Palisades of Vogt are located just peripheral to terminal capillary loops (arrows) of limbus.

especially in lightly pigmented individuals, the characteristic blunt-tipped vascular loops in the fibrovascular palisades mark their location (Fig 1A). These vessels are more prominent when the eye is inflamed (Fig 4).

The palisades are most numerous and obvious along the superior and inferior limbal regions, and least prevalent in the horizontal meridians. They may be few in number or may exceed

The configuration of the palisade zone is highly variable, and no limbal region is identical to any other, even in the same patient. The palisades appear to be more discrete in younger individuals and to be more prominent and regular along the lower limbus than at the upper limbus (Fig 5A and B). The overall configuration in one eye tends to resemble that in the other eye, but the symmetry is never exact.


FIGURE 1 Precise focusing at high magnification is necessary if palisades of Vogt are to be observed. A: Each palisade (arrows) contains a radially oriented vascular complex; cf, Fig 1B. Open arrow indicates marker vessel for orientation and comparison with Fig 1B. The angiogram is shown in Fig 7. 8; Same area as Fig 1A, but focused slightly more superficially. The palisades cannot be seen. Open arrow indicates marker vessel for orientation and comparison with Fig 1A. C: Limbal area at low magnification only faintly shows palisade zone as series of short, radially oriented and parallel stripes (arrow). Palisades of Vogt 159

9

FIGURE 3 The palisades of Vogt are more easily discerned when moderately dense limbal melanosis is present. A: East Indian limbus; palisades outlined by melanin-containing cells ofinterpalisade zones are easily seen in diffuse illumination. B: European limbus; palisades are seen well only in scleral scatter.

FIGURE 4 Vessels (arrows) of the palisades are dilated and more visible when the conjunctiva is inflamed, as in case of adenoviral conjunctivitis. 160 Goldberg

FIGURE 5 Palisades are more prominent and regular along lower limbus than at upper limbus. A: Composite photograph of lower limbus of eye whose upper limbus is shown in Fig 5B. B: Composite photograph of upper limbus of eye whose lower limbus is shown in Fig 5A.

In non- or lightly pigmented eyes, the palisades appear white and translucent. Their edges are highlighted, possibly due to the contrast imparted by adjacent ridges of epithelial cells in the interpalisades. Thus each palisade may appear double—contoured. In more heavily pigmented eyes the palisades are easily identified because of rows of brown pigment, presumably due to adjacent epithelial cells containing melanin that are seen end on.

The shape of individual palisades is also extremely varied. The commonest configuration is a long, narrow rectangle, but tiny circles or ovals may also be seen. The latter shapes are probably identical to the "basal crypts” of Graves,8 and often contain a central red dot, presumably a Palisades of Vogt 161


FIGURE 6 The shape of individual palisades varies considerably. A: Typical narrow rectangles are seen at right, and more unusual dot and oval shapes are seen at left. B: Palisades shaped like H’s, V's, K’s, or Y's may be seen, along with complex trabecular configurations.

palisadal vessel seen end on. The long, narrow, rectangular palisades often interconnect, forming Y-, H-, X-, or K-shaped patterns (Figs 5, 6). Sometimes, more extensive connections give a trabecular appearance.

Measurements of the length and width of the palisades and interpalisades from 12 normal subjects are shown in the Table, and indicate that the fibrovascular bundles are narrower than the epithelial rete ridges. The average length of the palisades in our subjects was 0.36 mm : 0.09 SD (range: 0.25 to 0.59 mm), and their average width was 0.04 mm : 0.007 SD (range: 0.03 to 0.05 mm). The variation of these dimensions is indicated by the coeflicients of variation, which were 26.7% for length and 18.5% for width. The corresponding measurement for the width of the epithelial interpalisades was as follows: average width, 0.07 mm : 0.02 SD (range: 0.05 to 0.10 mm). The coefficient of variation was 22.7%. The length of the interpalisades could not be determined because of the lack of discrete margins.


TABLE: PALISADE MEASUREMENTS (n = 12 NORMAL SUBJECTS)

LENGTH WIDTH INTERPALISADAL WIDTH

Mean 0.036-mm 0.04 mm 0.07 mm Range 0.25-0.59 mm 0.03-0.05 mm 0.05-0.10 mm SD 0.09 mm 0.007 mm 0.02 mm Coeflicient of

variation 26. 7% 18. 5% 22. 7% cf, Duke-Elder &

Wybar26 — — 1.5-2.0 mm

Vogta 0.07-0.9 mm 0.03-0.05 mm 0.1-0.15 mm

Cravess 0. 5-1.25 mm — —-— 162 Goldberg

AN GIOGRAPHIC FINDINGS

The small size, rapid filling, and complexity of the limbal vasculature make angiographic interpretation somewhat difficult. The palisadal vessels, however, because of their parallel, radial orientation can be distinguished, and the extent of their ability to contain fluorescein intraluminally can be characterized. The palisadal vessels are but one microvascular subsystem derived from the anterior ciliary arteries.

As described in detail by Bron and Easty,9 the sequence of How in the external portion of the globe’s anterior segment is as follows: (1) The anterior ciliary arteries fill first, and give rise to episcleral branches directed anteriorly toward the limbus. (2) Three distinct vascular subsystems then fill, as follows, and ultimately drain into the episcleral venous plexus: .

a. The recurrent conjunctival arteries, supplying the paralimbal con junctiva for a distance of about 3 to 6 mm from the limbus;

b. the marginal arcades (terminal capillary loops) of the cornea (the most

centrally located vessels); and

c. the palisadal vessels.

The palisadal vessels fill extremely quickly, and, with the techniques employed, the arterial and venous components of the hairpin vascular loop occupying the palisade cannot be distinguished. The functional competence of their endothelial linings appears more developed than that of other episcleral and conjunctival vessels, in that leakage of fluorescein occurs later than it does in these other vessels and apparently to a lesser extent (Fig 7A and B). The onset and amount of leakage roughly parallel the courselof events in the marginal arcades (Fig 7).

As leakage from the normal palisadal vessels proceeds, the palisades gradually become hyperfluorescent, and the vessels themselves eventually stand out in negative relief (Figs 8, 9). The late hyperfluorescence outlines the full extent of the palisadal fibrovascular tissues and allows them to be Visualized more clearly. The interpalisades also become more visible because they are relatively hypofluorescent at this stage. The lack of hyperfluorescence that characterizes the interpalisades is probably due to their remoteness from leaking vessels and the lesser amount of fibrovascular connective tissue in the substantia propria underlying the epithelial rete ridges. The rete ridges themselves may have inter- or intracellular barriers to diffusion of fluorescein.

In eyes characterized by anterior segment inflammation, particularly infectious conjunctivitis such as that caused by adenoviruses, the amount of fluorescein leakage and hyperfluorescence are much greater (Fig 8). All the paralimbal vessels dilate, and the palisadal vessels are more easily seen. Palisades of Vogt 163

FIGURE 7 Angiogram of lower limbal region shown in Fig 1A. A: Vessels of palisades (triple white arrows) fill extremely quickly, at about same time as terminal capillary loops (single white arrow). Both sets of vessels leak fluorescein slightly, and to lesser extent than bulbar vessels of conjunctiva (open black arrows). B: Later venous stage of angiogram seen in Fig 7A. Very little additional leakage is seen from vessels of palisades and from terminal capillary loops of the marginal arcades, whereas bulbar conjunctiva is intensely hyperfluorescent due to extreme leakage. 164 Goldberg

FIGURE 8 Angiogram of normal limbus. A: Early arterial phase. Vessels of palisades (triple arrows) have not yet become perfused. Open white arrow indicates same vessel in all phases of angiogram. B: A few seconds later, vessels of palisades contain fluorescein (triple arrows), but there is almost no leakage. Other bulbar vessels of conjunctiva have begun to leak (double arrows). C: Early venous phase shows mild leakage from vessels of palisades (triple arrows). D: Late venous phase shows little increase in leakage from vessels of palisades (triple arrows), although leakage from larger vessels of conjunctiva has increased markedly.

Furthermore, the palisadal tissue appears to enlarge, possibly because of inflammatory edema and cellular infiltration, and the palisades become wider than the interpalisades contrary to their normal proportions.

HISTOLOGIC FINDINGS

Routine histology of the human limbus confirms the presence of fibrovas— cular palisades interdigitating with epithelial rete ridges (Fig 10). The palisades contain nerves, arteries, veins, and lymphatics. They are considerably narrower than the adjacent epithelial ridges when uninflamed. The epithelium of the ridge-shaped interpalisade ranges from about 10 to 15 cells in thickness or more, whereas that overlying the palisade may be only 2 to 3 cells thick or slightly more. In comparison, the corneal epithelium is about 5 cells in thickness. Palisades of Vogt 165

FIGURE 9 Angiogram of limbus from patient with adenoviral conjunctivitis. A: Mid-venous phase. Note hyperfluorescence of palisades (arrows) and negative image of their vessels. B: Late venous phase. Palisades (arrows) are enlarged when inflamed, and amount of fluorescein leakage is increased. 166 Goldberg

_ FIGURE 10 Histologic appearance of palisades of Vogt. The palisade is narrower than the interpalisade, and contains blood vessels (arrows) (hematoxylin and eosin). A: Limbus of 84-year-old woman. B: Another limbal area from same subject.

DISCUSSION

The palisade zone is clearly a specialized anatomic area, with differentiated ridges of thickened epithelium (the interpalisades) and a distinctive blood supply. The functions of these two components of the palisade zone, in

» both normal and abnormal states, can only be surmised at the present time. T‘

The palisadal vessels may serve to supply the metabolic needs of the large number of epithelial cells comprising the interpalisades, or may have some other fiinction. The interpalisades may represent a repository of replicating epithelial cells that slide inferiorly from the upper limbus and superiorly from the lower limbus where they exist in abundance. If so, they could normally serve to replace aging and dying cells in the central cornea and could be called upon to replace corneal epithelial cells that are destroyed by trauma or by other disease processes. A lack of a normal number of limbal epithelial cells or improper replication or migration might well be responsible for delayed epithelialization of the cornea in a wide variety of disease states; eg, alkali burns, etc. The radial distribution of the palisades and interpalisades along the superior and inferior limbus may also explain the characteristic verticillate pattern of the corneal epithelium in such disorders as F abry’s disease and drug-induced degeneration.7 In these circumstances one may theorize that the radial epithelial ridges at the limbus send columns of cells onto the surface of the cornea, causing their typical curvilinear distribution.

Whatever their function, the anatomy of the palisades and interpalisades is remarkably similar to the dermatoglyphic (“skin carving”) configuration of the cutaneous epithelium on the plantar and volar surfaces of the hands Palisades of Vogt 167

and feet. Here, as in the limbus, parallel rows of epithelial rete ridges interdigitate with cords of fibrovascular connective tissue. In analogy with the skin, the characteristic limbal anatomy can be called “conjunctivoglyphics” (“conjunctival carvings”) or “limboglyphics." There are several additional points of similarity. The glyphics are not present on all skin surfaces, nor are they found throughout the conjunctiva. Holocrine glands or cells (sebaceous in the skin; goblet cells in the conjunctiva) are missing from both of these specialized structures. The ridge patterns are unique to each individual in the skin (eg, fingerprints) and also appear unique in the conjunctiva. One difference between the dermatoglyphics and conjunctivoglyphics is the presence of eccrine (sweat) gland openings on the epithelial rete ridges in the former, and their absence in the latter.

In the skin there are characteristic changes in the ridge patterns in different diseases (eg, trisomies, chromosomal deletions, ectodermal dysplasia, congenital rubella,‘ nail-patella syndromem); some minor differences between males and females; and some racial differences in the types of individual ridge patterns. “'16 Whether or not the study of conjunctivaglyphics proves to be as clinically or genetically as rewarding as that of dermatoglyphics remains to be seen. In any event it would be desirable to study the palisades and interpalisades to determine the following: if there are age, race, sex, or twin differences; if there are associations with chromosomal diseases; and if there are characteristic changes with such acquired diseases as recurrent corneal erosions, delayed graft epithelialization, chemical burns, melting diseases of the limbus, and various limbal operations including fomix- and limbal-based flaps of the conjunctiva.

It is of interest that a large number of previous angiographic studies1’9’17"°‘4 have failed to visualize or describe the vasculature of the palisades of Vogt. Good clinical descriptions and diagrams may be found in the work by Vogt, himself,3 by Craves,8 by Hogan et al,‘°‘5 and by DukeElder and Wybar.26 The fact that fluorescein leakage from the palisadal vessels occurs relatively late in the angiographic sequence and is relatively mild suggests that some intercellular junctional complexes in the endothelium may be functionally competent and/or that there are few, if any, endothelial fenestrations. In an electron microscopic study of conjunctival vessels Hogan was able to demonstrate some zonulae occludentes, only a few cytoplasmic fenestrations, good basement membrane formation, and a few pericytes. 25 In any event, the angiographic appearance of the palisadal vessels suggests that this distinctive microvasculature has functional properties different from those of the more peripheral bulbar conjunctiva. 168 Goldberg

SUMMARY

The palisades of Vogt are distinctive normal features of the human corneoscleral limbus. Our clinical studies indicate that they are more discrete in younger and in more heavily pigmented individuals, and that they appear more regular and prominent at the lower limbus than at the upper limbus. They are seen only infrequently in the horizontal meridian. There is some symmetry (though it is not exact) from one eye to the other in the same person. The anatomy of the palisades appears to be unique for a given individual. In this respect, as well as in their microscopic anatomy, the palisades of Vogt appear comparable to fingerprints, and the term “conj unctivoglyphics” (“conjunctival carvings”) or “limboglyphics” is suggested in analogy with “dermatoglyphics.”

The palisades of Vogt have a distinct vasculature with narrow, barely visible, arterial and venous components of radially oriented hairpin loops. Angiography reveals that these vessels leak fluorescein relatively late and only to a moderate extent. They respond to inflammation by dilatation and gross breakdown of their physiologic barrier properties.

The functions of the palisades of Vogt are not known with certainty, but their interpalisadal epithelial rete ridges may serve as a repository for corneal epithelial cells. They may thus be important in both aging and diseases of the cornea.

REFERENCES

1. Bron A], Goldberg MF: Clinical features of the human limbus, in Trevor-Roper P (ed): The Cornea in Health and Disease: Proceedings of the Vlth Congress of the European Society of Ophthalmology. London, Academic Press Inc, 1981.

2. Aurell G, Komerup T: On glandular structures at the comeo-scleral junction in man and

swine: The so-called “Manz glands.” Acta Ophthalmol 27:19, 1949.

Vogt A: Atlas of the Slitlamp-Microscopy of the Living Eye. Berlin, Springer, 1921.

Dobree JH: Superficial perilimbal vessels in the normal and congested eye. Br ]

Ophthalmol 34:720, 1950.

5. Maumenee AE: Repair in the cornea, in Montagna W, Billingham RE (eds): Advances in Biology of Skin. New York, Macmillan Co, 1964, vol 5.

6. von Heydenreich A: Die Zellmigration im Bereich der Hornhaut. Ber Dtsch Ophthalmol Ces 62:287, 1959.

7. Bron A]: Vortex patterns of the corneal epithelium. Trans Ophthalmol Soc UK 93:455,

1973.

Graves B: Certain clinical features of the normal limbus. Br] Ophthalmol 18:305, 1934.

Bron A], Easty DL: F luorescein angiography of the globe and anterior segment. Trans

Ophthalmol Soc UK 90:339, 1970.

10. Verbov ]: Clinical significance and genetics of epidermal ridges: A review of der matoglyphics. ] Invest Dermatol 54:26l, 1970. 11. Miller JR: Dermatoglyphics. ] Invest Dermatol 60:435, 1973.

12. Holt SB: The significance of dermatoglyphics in medicine: A short survey and summary. Clin Pediatr 12:47l, 1973. '

99°

599° Palisades of Vogt 169

13. Preus M, Fraser F C: Dermatoglyphics and syndromes. Am] Dis Child 124:933, 1972.

14. Cherrill FR: The Finger Print System at Scotland Yard. London, Her Majesty's Stationery Oflice, 1954.

15. Schaumann B, Alter M: Dermatoglyphics in Medical Disorders. New York, SpringerVerlag, 1976. ’

16. Holt SB: The Genetics of Dermal Ridges. Springfield, Ill, Charles C Thomas, 1968.

I7. Easty DL, Bron A]: F luorescein angiography of the anterior segment: Its value in corneal disease. Br J Ophthalmol 55:671, 1971.

18. Mitsui Y, Matsubara M, Kanagawa M: Fluorescence irido-corneal photography. Br I Ophthalmol 53:505, 1969.

19. Fetkenhour CL, Choromokos E: Anterior segment fluorescein angiography with a retinal fundus camera. Arch Ophthalmol 962711, 1978.

20. Bruun-Jensen J: F luorescein angiography of the anterior segment. Am ] Ophthalmol 67:842, 1969.

21. Amalric P, Rebi E: New indications of fluorescein angiography of the anterior segment of the eye: IV. Several examples of scleral and corneal pathology. Ann Ocul (Paris) 204:73l, I971.

22. Marsh R], Ford SM: Blood flow in the anterior segment of the eye. Trans Ophthalmol Soc

UK 1002388, 1980.

Talusan ED, Schwartz B: Fluorescein angiography: Demonstration of flow pattern of

anterior ciliary arteries. Arch Ophthalmol 99:1074, 1981.

M inatoya H, Acacio I, Goldberg MF : F luorescein angiography of the bulbar conjunctiva

in sickle cell disease. Ann Ophthalmol 5:980, 1973. Hogan M], Alvarado ]A, Weddell IE: Histology of the Human Eye: An Atlas and Textbook. Philadelphia, WB Saunders, 1971.

26. Duke-Elder S, Wybar KC: The Anatomy of the Visual System: System of Ophthalmology.

London, Henry Kimpton, 1961, vol 2.

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DISCUSSION

DR VVILLIAM H SPENCER. The authors have carefully studied the biomicroscopic appearance, vascular dynamics and anatomic substrate of the specialized epithelial and subepithelial fibrovascular structures located at the limbus known as the “palisades of Vogt. " The authors note considerable variation in pattern, distribution and number of ridge-like palisades from one person to another and suggest that, like fingerprints, the limbal palisades are distinctive for a given individual. The authors speculate about the function of the epithelial and vascular components noting that the thick layer of inter-palisadal epithelial cells may serve as a depot of cells ready to migrate onto the cornea to replace diseased or destroyed corneal epithelial cells, and they suggest that the vessels serve to nourish these cells.

In histologic sections of normal skin the border between the dermis and epidermis is irregular due to the presence of dermal papillae that extend upward into the epidermis. The ridges of epidermis separating the papillae are known as rete ridges. This pattern is relatively inconspicuous wherever the skin is loosely adherent to underlying tissues, but is quite prominent at sites of firm subepithelial adhesions. In the hand the skin of the dorsum is quite “loose” and has relatively few rete ridges, but the firmly attached palmar surface of the skin contains many ridges. Similarly the thin skin of the eyelid surface containing epithelium of uniform 170 Goldberg

thickness is readily “ballooned up" by a subepithelial injection of fluid until the lid margin is reached where firm rete ridges and dermal papillae inhibit further fluid dissection. These anatomic specializations are also found in mucous membrane, especially at zones of transition and attachment. Doctors Goldberg and Bron have called our attention to the anchoring sites of the conjunctiva at the limbus. Corresponding attachments are found where the conjunctiva adheres to the tarsus and to the lid margin at the mucocutaneous junction. In the tarsus the spread of vascular and perivascular inflammation is to a degree limited by these structures causing characteristic papillae to form, some with a “paving block" configuration. The spread of inflammatory transudate from the vessels of the limbal palisades may also be in part limited by the inter-palisadal attachments. Perhaps this accounts for the papillary configuration of the circumscribed elevations occasionally seen at the limbus in individuals with vernal kerato-conjunctivitis. i ‘

The authors have provided us with interesting data pertaining to the fluorescein leakage pattern from normal palisadal vessels. It is to be hoped that they will continue this investigation since so little is known about the responses of these vessels to a variety of stimuli and the role that they play in such diverse conditions as peripheral corneal immune reactions and the development of a pannus.

One of the most intriguing aspects of this study is the suggestion that the thick layer of inter-palisadal epithelial cells can serve as a repository for cells that can migrate onto the cornea to replace diseased or destroyed corneal epithelial cells. Normally the epithelial cells of the cornea are, in part, replaced by cells from the basal layer where cell division takes place. Undoubtedly central migration of peripheral cells also occurs. As evidence of this phenomenon the authors draw our attention to the characteristic vertically oriented curvilinear pattern of corneal epithelial opacification that occurs in F abry’s disease and after utilization of drugs such as Amiodarone or chloroquine. Additional evidence is seen in another condition occurring primarily in blacks, known as striate melanokeratosis where limbal pigment bearing cells migrate toward the center of the cornea after chronic inflammation or injury. I would like to ask if the authors have observed the pattern of opacification in Fabry's disease to begin at the superior and inferior limbus and to advance centrally. These photographs from the collection of Doctor Richard Abbott at the Pacific Medical Center in San Francisco show the characteristic pattern of corneal epithelial opacification in Fabry’s disease and after use of Amiodarone. The participation by peripheral cells in the process is diflicult to determine. I would assume that the cells most likely to become affected would be those that are most active metabolically, and would expect the opacity to arise centrally as well as peripherally. Perhaps an animal model using a radiomarker, such as tritiumlabeled thymidine, could be used to study the participation of the inter-palisadal epithelial cells in these conditions, and in the normal turnover of corneal epithelial cells.

I very much appreciate the opportunity to discuss this fine contribution to the literature and wish to thank the authors for sending me their manuscript well in advance of the meeting. Palisades of Vogt . 171

DR GEORGE SPAETH. One observation on gonioscopy is that the posterior trabecular meshwork is almost always less pigmented in the 3:00 and 9:00 o'clock positions than elsewhere. I have never been able to understand this. I wonder if Doctor Goldberg believes that there is less flow of aqueous out of these particular areas, which may explain this peculiar distribution of pigmentation or rather lack of pigmentation in these areas.

DR MORTON GOLDBERG. Thank you. With respect to Doctor Spaeth’s query, I have no explanation of that observation. We do not think that it would be directly attributable to the palisades. With respect to Doctor Spencer’s comments, I think they were extremely valuable. The labelling studies would, in a proper subhuman primate, probably answer the question as to the migration of pericorneal cells onto the center of the cornea. There is no doubt, from a variety of animal as well as human studies, that surface corneal epithelial cells come not only from the basal layer of the corneal epithelium but also from the pericomeal limbus. The pericomeal limbal cells have a higher mitotic rate than those in the center of the cornea. One might theorize, therefore, that the more rapidly reproducing cells might migrate into zones where the reproduction rate is slower. That would explain the appearance we see in the otherwise dissimilar whirlpool or vortex patterned dystrophies of the corneal epithelium. This group of diseases is extremely heterogeneous from the etiologic point of view. There are, for example, inherited storage diseases, such as Fabry's disease, in which macrolipid marks the presence of the apparently migrating corneal epithelial cells. One sees the same biomicroscopic appearance in toxic keratopathies, such as those caused by chloroquine and Amiodarone. One sees the same thing as a normal manifestation of epithelial slide in heavy pigmented individuals (striate melanokeratosis). It would seem that the common denominator of these quite dissimilar diseases would involve the pattern of cell migration, because these conditions have virtually nothing else in common. However, the proof is in the pudding, and we have not performed the experiments suggested by Doctor Spencer. I would agree that further work is indicated, and I hope that many of the members would proceed with it.



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