A C T A O P H T H A L M O L O G I C A

61 (1983) 467-473

Department of Ophthalmology’ (Head: N . Ehlers), t b h u Kommunehospital, University of Aarhzls, Arhzls, Denmark

THE CENTRAL CORNEAL THICKNESS IN PATIENTS WITH HORNER’S SYNDROME

BY

PER JULIUS NIELSEN

In 14 patients with unilateral Horner’s syndrome there was a significant increase in central corneal thickness on the affected side (mean difference 4.86 pm f SEM 1.71 pm; P < 0.02). It is suggested that the sympathetic nerve supply of the eye is of importance for corneal hydration. Different possible mechanisms are discussed. Among the investigated patients no permanent ocular hypotonia or hyperaemia was found. On slit-lamp investigation there was no corneal change. The corneal sensitivity was equal on both sides.

Key words: Horner’s syndrome -corneal hydration - central corneal thickness - sympathetic nerves - adrenergic - membrane receptor - cyclic - AMP.

Active metabolic functions involving cyclic-AMP have been demonstrated in isolated animal corneas as well as in human corneas (Walkenbach et al. 1980, 1981, 1982 ; Zadunaisky et al. 1973). Receptors activating the enzyme adenylate cyclase have been shown in the corneal epi- and endothelial surface-membranes (Walken- bach et al. 1980). Receptors of this kind are mainly beta-adrenergic, but also prostaglandin and serotonergic receptors seem to be involved (Beitch et al. 1974; Walkenbach et al. 1982; Neufeld 1982).

The source of the agonists in vivo is not known, but it may be nervous (Klyce 1982; Tervo et al. 1976) as well as hormonal, reaching the cornea by diffusion from nearby vascular or nervous structures (Zadunaisky 1973).

In an attempt to relate these new observations from in vitro studies to the in vivo situation, patients with unilateral Horner’s syndrome were chosen for the present

Received on October 22nd, 1982.

467 30*

Nielsen The corneal thickness and Horner's syndrome

study t o see if, by measuring the corneal thickness, the ocular par t of the

sympathetic nervous system has any demonstrable effect o n corneal hydration and water metabolism.

Material and Methods

Fourteen patients with unilateral Homer's syndrome were chosen for the study. Age range was 18-70 years, mean 46 years. Femaleimale ratio was 1014. Duration of oculosympathetic paresis ranged from 6 months to 36 years, mean 7.2 years. There were 9 patients with the right and 5 with the left eye affected. Before any aximation had taken place, the patients had their central corneal thickness measured to avoid the bias of knowing the side of the Horner's syndrome. Both sides were measured, the unaffected side serving as control.

A Haag-Streit slit lamp with pachometer attachment was used throughout the experiments. The measuring procedure was done in the way described earlier by Olsen et al. (198 1). All readings were taken between 12 and 14 p.m. The patients were evaluated in the slit lamp

ACCT p y 15

10

8

6

4

2

0

-2

-4

-6 t 1 ' 2 ' 3 ' 4 ' 5 ' 6 ' 7 ' 8 ' 9 ' 1 0 ' 1 1 i 2 ' 1 3 ' 1 4 ' PAT NO

- Fag. I

Differences in central corneal thickness (CCT) (Horner's syndrome eye - control eye) Mean difference (G? SEM) WAS 4.86 ? 1.71 pm. P < 0.02 by a paired t-test.

468

Nielsen The corneal thickness and Horner’s syndrome

n I O P m m Hg

+5

0 -

- 5

-

Fig. 2. Differences in applanation pressure (IOP) (Horner’s syndrome eye -control eye).

Mean difference (M f SEM) WAS 0.23 iz 0.47 mmHg - not significant by a paired t-test

without and with fluorescein staining. The intraocular pressure was measured with the Goldmann applanation tonometer. The corneal sensibility was measured with the ‘Cochet & Bonnet’ aesthesiometer with scale readings from 0.5-6.0 cm (0.12 mm nylon monofilament). Measurement was done centrally on the cornea. Patients with unassociated conditions - ocular or systemic diseases - and patients on medical treatment known or suspected to interfere with the corneal thickness readings were excluded from the study.

Resu I ts

Eighteen patients have been investigated, and 14 entered the study. Four have been dismissed, one because of wrong diagnosis (Adie pupil), 2 because of intensely reduced corneal sensitivity from known central trigiminal lesion with keratitis, and one because of endothelial corneal dystrophy.

The mean thickness on the affected side was 528.86 pm k 6.03 pm (a f SEM) and

469

Nielsen The corneal thickness and Horner's syndrome

n sensibility cm

6 5 4 3 2 1 0 -

- 1 - 2 - 3 - 4 - 5 - 6 -

1 ' 2 ' 3 ' 4 ' 5 ' 6 ' 7 ' 8 ' 9 '1o'11'12~13'14' PAT NO

Fig. 3. Differences in central corneal sensibility (Cochets & Bonnets aesthesiometer) (Horner's syndrome eye - control eye). Mean difference (Rf SEM) WAS 0.23 f 0.12 cm - not

significant by a paired t-test.

on the contralateral side 524.00 pm f 6.73 pm (7 f SEM). When evaluated by a paired t-test a significant increase in the corneal thickness was found on the side with the oculosympathetic paresis as compared with the non-affected side (mean difference 4.86 pm, SEM f 1.71 pm; P < 0.02) (Fig. 1).

The mean intraocular pressure on the side with oculosympathetic paresis was 13.77 + 0.77 (K + SEM) mmHg compared with 14.00 f 0.87 fi f SEM) mmHg on the unaffected side (not significant by paired t-test) (Fig. 2). The mean sensibility on the affected side was 5.77 f 0.12 (W k SEM) cm compared with 6.0 f 0.0 (7 k SEM)

cm on the unaffected side (not significant by paired t-test) (Fig. 3). No conjunctival injection was seen on the side with oculosympathetic paresis, or on the control site. And on slit-lamp examination, including fluorescein staining, no part of the cornea showed any change in either site.

470

Nielsen The corneal thickness and Horner’s syndrome

Discussion

The present study shows a small, but statistically significant increase in central corneal thickness, suggesting that the sympathetic nervous system is of importance for the regulation of corneal thickness. The observed increase in thickness is probably due to an increase in the corneal water content.

It has been suggested that the corneal swelling is opposed by ionic pumps producing osmotic work (Zadunaisky 1973 ; Mishima 1982). In isolated corneas adrenergic substances have been shown to be specific agonists of receptors in the epithelium (Zadunaisky 1973; Neufeld 1982) and endothelium (Walkenbach 1982) stimulating the production of cyclic-AMP. Also, it has been shown that the animal cornea transports chloride ions from aqueous to tear side by a pump located in the epithelium, which can dehydrate a partly swollen cornea, and that this was activated by adrenaline and cyclic-AMP (Zadunaisky 1973 ; Beitsh 1973).

Nerves containing biogenic amines have been demonstrated in the cornea in many laboratory animals by fluorescein staining technique (Ehinger 197 1; Ehinger 8c SjGberg 198 1; Tervo et al. 1976). Horseradish peroxidase injected into the cornea is transported to cell bodies of the superior cervical ganglion (Klyce 1982). The existence of adrenergic nerves in the adult human cornea has, however, been disputed, and has only been demonstrated in human embryos (Ehinger 197 1).

The perilimbal vessels are richly supplied with adrenergic nerves (Ehinger 197 I ) , and when patients with Horner’s syndrome are seen in the acute state, hyperaemia of these and conjunctival vessels may be seen, but this usually fades away in a few weeks (Keane 1979; Thompsson 1977).

In the present study no conjunctival or perilimbal hyperaemia was registrated, which agrees with the above statement, since none of the investigated patients have had their Horner syndrome for less than 6 months.

Nothing is as yet known about the existence and possible role in the regulation of corneal metabolism of adrenergic substances in the aqueous humour (Zadunaisky 1973). In the normal homostatic state several of the above discussed mechanisms may be functioning at the same time.

No correlation was found between the existence time of the Horner’s syndrome and changes in corneal thickness. Unfortunately, no patients have been investigated in the acute state. The patients have not been tested regularly according to the affected neuron in the sympathetic chain.

Relationship between intraocular pressure and corneal thickness is well known (Ehlers et al. 1975). Ocular hypotonia ws not found in the present study. Ocular hypotonia, like hyperaemia is only transient in patients with Horner’s syndrome and disappears a few weeks after the acute state (Keane 1979; Thompsson 1977).

47 1

Nielsen The corneal thickness and Horner’s syndrome

The main significance of this observation in the present study, is that the increased corneal thickness could not be based on ocular hypotonia.

Other functions than regulation of corneal hydration have been suggested to be regulated by adrenergic stimulation of the corneas. Ehinger (1971) suggested that the adrenergic nerves in the cornea might modify the sensitivity stimulus of the cornea. This is not indicated from the present results using the ‘Cochet & Bonnet’ aesthesiometer.

Clearly, more work is needed before the regulation of corneal metabolism is understood, but the cornea seems not to be as isolated in the vivo state as earlier believed.

References

Beitch B R, Beitch I & Zadunaisky J A (1974): The stimulation of chloride transport by prostaglandins and their interaction with epinephrine, theophyllamine and cyclic-AMP in the corneal epithelium. J Memb Biol 19: 381 -396.

Candia 0 A, Podos S & Neufeld A H (1979): Modification by timolol of catecholamine stimulation of chloride transport in isolated corneas. Invest Ophthalmol Vis Sci 18: 69 1-695.

Ehinger B (197 1): A comparative study of the adrenergic nerves to the anterior eye segment

Ehinger B & Sjoberg N 0 (197 1): Development of the ocular adrenergic nerve supply in man

Giles C L & Henderson J W (1958): Horner’s syndrome: An analysis of 216 cases. Am J

Keane J (1979): Oculosympathetic paresis: analysis of 100 hospitalized patients. Arch Neurol

Klyce S D (1982): Cyclic AMP. Control of transport in the cornea. ARVO p 13. Mensher J H (1974): Corneal nerves - review. Surv Ophthalmol 1 19: 1 - 18. Mishima S (1982): Clinical investigations on the corneal endothelium. Am J Ophthalmol 93:

Neufeld A H (1982): Adrenergic and serotonergic stimulated cyclic AMP Synthesis in the corneal epithelium. ARVO p 13.

Neufeld H, Zawistowski K A, Page E D & Bromberg B B (1979): Influences on the density of P-adrenergic receptors in the cornea and iris-ciliary body ’of the rabbit. Invest Ophthalmol Vis Sci 17: 1069- 1075.

Olsen T (1982): Specular microscopic investigations on corneal endothelium and its involve- ment in corneal oedema. Acta Ophthalmol (Copenh). Suppl155.

Olsen T, Nielsen C B & Ehlers N (1980): On the optical measurement of corneal thickness. I. Optical principle and sources of error. Acta Ophthalmol (Copenh) 58: 760-766.

Olsen T, Nielsen C B & Ehlers N (1980): On the optical measurement of corneal thickness. 11. The measuring conditions and sources of error. Acta Ophthalmol (Copenh) 58: 975-984.

Tervo T & Palkama A (1976): Sympathetic nerves in the rat cornea. Acta Ophthalmol (Copenh) 54: 75-84.

of some primates. Z Zellforsch Mikroskop Anat 116: 157- 177.

and guinea-pig. Z Zellforsch Mikroskop Anat 118: 579-592.

Ophthalmol46: 289-296.

36: 13.

1-29.

472

Nielsen The corneal thickness and Horner’s syndrome

Tervo K, Tervo T & Palkama A (1978): Pre- and postnatal development of catacholamine- containing and cholinesterse-positive nerves of the rat cornea and iris. Anat Embryo1 154: 253-265.

Thompson H S (1977): Diagnosing Horner’s syndrome. Trans Am Acad Ophthalmol Otolaryngol83: 840-842.

Walkenbach R J, LeGrand R D & Bar R E (1980): Characterization of adenylate cyclase activity in bovine and human corneal epithelium. Invest Ophthalmol Vis Sci 19: 1080- 1086.

Walkenbach R J & LeGrand R D (198 1): Regulation of cyclic-AMP-dependent protein kinase and glycogensynthase by cyclic-AMP in the bovine cornea. Exp Eye Res 33: 1 1 1 - 120.

Walkenbach R J & LeCrand R D (1982): Adenylcyclase activity in the bovine and human corneal endothelium. Invest Ophthalmol Vis Sci 22: 120- 124.

Walkenbach R J & LeGrand R D (1982): Inhibition of adenyl-cyclaseactivity in the corneal epithelium by antiinflammatory steroids. Exp Eye Res 34: 161 - 168.

Zadunaisky J A, Lande M A, Chalfie M & Neufeld A H (1973): Ion pumps in the cornea and their stimulation by epinephrine and cyclic-AMP. Exp Eye Res 15: 577-584.

Author’s address: Per Julius Nielsen, (djenafdeling J, Arhus kommune hospital, 8000 Arhus.

473