British Journal of Ophthalmology, 1983, 67, 297-301

Ocular sympathetic denervation associated with ocularhypertension: a case report

D. J. BRAZIER

From the Department of Ophthalmology, St Thomas's Hospital,, London SE]

SUMMARY The exact function of the sympathetic nervous system in the regulation of intraocularpressure remains unclear. Many observers have noted reduced intraocular pressure in eyes whosesympathetic supply has been interrupted. A case of ocular sympathetic denervation associated withocular hypertension is reported. Reports on the relationship between intraocular pressure andsympathetic denervation are reviewed and their relevance to this case discussed.

Case report

A retired man aged 64 was referred to GreenwichDistrict Hospital in November 1980 following a visitto his optician. Marked asymmetry of intraocularpressure (IOP) had been noted on noncontacttonometry (right eye 8 mmHg, left eye 22 mmHg).The patient had no visual symptoms and gave no pastor family history of eye disease. He had undergonebilateral cervical sympathectomy in 1953 forRaynaud's phenomenon, which had subsequentlyimproved. On direct questioning he admitted that theright upper lid had tended to droop since theoperations and that his face did not sweat, even inwarm weather.On examination he was a fit man for his age with

sympathectomy scars in both supraclavicular fossae.With a small hypermetropic correction his visualacuities were right 6/6 N5 and left 6/6 N5. There was aCorrespondence to Dr D. J. Brazier. Moorfields Eye Hospital. CityRoad. London ECIV 2PD.

mild right ptosis with normal eye movements. Theright pupil was smaller than the left (Fig. 1) but bothreacted normally to light. Right IOP was 10 mmHg,left 28 mmHg by applanation tonometry. Bothanterior chamber angles were open and showed nosignificant pigmentation on gonioscopy. Visual fieldswere normal. The optic discs were not entirelysymmetrical (Fig. 2) but were thought in the absenceof field loss to be consistent with a diagnosis of leftocular hypertension. He also had a clinical rightHorner's Syndrome.Three weeks later the left IOP was further elevated

at 40 mmHg. Treatment of this eye was indicated andhe started pilocarpine drops 4% qds and adrenalinedrops 1% bd. This regimen adequately controlled theIOP. The right IOP remained normal withouttreatment.

In March 1982 further studies were undertaken atSt Thomas's Hospital to elucidate the nature of thesympathetic denervation and possibly its relationshipto the uniocular hypertension. The patient was asked

Fig. I This photograph was takenin white light in the studio. Rightptosis and miosis are visible.

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Pupil diameter (mm)

4

3

2

4,

0 5

Fig. 2B

Fig. 2 (A) right and (B) left optic discs were not entirelysymmetrical, but were considered normal.

to discontinue his drops for 2 weeks and was thenre-examined. With the eyes in the primary position,vertical heights of the palpebral fissures were right 8mm and left 10 mm, while widths were equal. Noenophthalmos was detected. Visual acuitiesremained normal. Right miosis was still clinicallyvisible. Right IOP was 10 mmHg, left 24 mmHg.Gonioscopy and visual fields, as assessed byFriedmann Central Field Analyser and Goldmannperimetry, were unchanged. The slight asymmetry ofthe optic discs persisted. No facial sweating was

demonstrable on either side with quinizarine dustingpowder. Quinizarine is a mauve powder whichbecomes magenta coloured when damp. It was usedby Giles and Henderson in their analysis of 216 casesof Horner's syndrome.'

Photographic studies showed bilateral pupillarydilatation lag2 and that the left pupil dilated less thanthe right in reduced illumination. In the absence ofany iris abnormality visible on the slit-lamp therelative immobility of the left pupil was taken to besecondary to long-term pilocarpine application.

Fig. 3 Pupildiametersofright( ) and left (--eyes with reflexes elicited by light stimulation (+) of the lefteye. There is delayed redilatation on both sides.

Infrared pupillometry confirmed the presence ofpupillary dilatation lag (Fig. 3). Pupillometry was alsoperformed after instillation, on different occasions, ofcocaine drops 10%, hydroxyamphetamine drops0-5%, and phenylephrine drops 2%. Theseexaminations were performed in a standardised wayseparated by intervals of at least 7 days. The onlytreatment given at this stage was oral acetazolamide,which was stopped 3 days prior to examinations.

Pupillometry on the right revealed reduced dilata-tion to cocaine (1-50 mm maximum increase in pupildiameter during one hour after instillation) withexaggerated dilatation to hydroxyamphetamine (3-00mm) and phenylephrine (4-42 mm). On the left sidedilatation to cocaine was also subnormal (1-30 mm),while dilatation to hydroxyamphetamine (1-20 mm)and phenylephrine (2-56 mm) was considered to bewithin normal limits. When these studies were

Table I Intraocular pressures and treatment

Date Intraocular pressure TreatmentmmHg (left eye only)

Right Left

2June 1980 8 22 NilI INov 1980 10 28 Nil3 Dec 1980 10 40 Nil17 Dec 1980 8 10 Gutt. pilocarpin. 4% qds

and Gutt. adrenalin. 1% bd9 Jan 1981 10 16 Gutt. pilocarpin. 4% qds

and Gutt. adrenalin. I% bd1 May 1981 8 20 Gutt. pilocarpin. 4% qds

and Gutt. adrenalin. 1% bd13 Nov 1981 9 12 Gutt. pilocarpin. 4% qds

and Gutt. adrenalin. 1% bd6Apr 1982 10 24 Nil20 Apr 1982 10 32 Nil18 May 1982 7 22 Gutt. timolol. 0-5% bd

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Ocular sympathetic denervation associated with ocular hypertension: a case report

complete, treatment was changed to timolol drops05% bd in the left eye.

Outflow facility in the right eye, by Granttonography, had been 0-12 ul mmHg-' min-' at thetime of the original presentation. Tonography wasnow repeated and produced values for outflow facilityof 0O14 ,lA mmHg-' min-' right eye and 013 ,ulmmHg-' min-' left eye. It has been demonstratedthat locally applied timolol does not alter outflowfacility,34 and treatment was therefore not stoppedprior to tonography.IOP measurement and treatment during relevant

periods are shdwn in Table 1.

Discussion

OCULAR SYMPATHETIC DENERVATION ANDINTRAOCULAR PRESSURE

The relationship between these two has been studiedboth in animal experiments and by clinicalobservation in humans who have suffered ocularsympathetic denervation.

Experimental studies, mainly in rabbits and cats,have been based on interruption of the cervicalsympathetic pathway proximal to the superiorcervical ganglion (preganglionic sympathectomy) ordistal to it (postganglionic sympathectomy). Thelatter lesion is also produced by destruction orexcision of the superior cervical ganglion.

In 1948 Jaffe' reported that section of the cervicalsympathetic nerves in cats produced a reduction ofIOP lasting 2 days. Over several weeks he noted thatpostganglionic sympathectomy caused persistentdepression of IOP, while preganglionic sym-pathectomy resulted in normal or elevated IOP. Theshort-term reduction of IOP following sympathec-tomy was subsequently confirmed and studied indetail by many observers; long-term effects of sym-pathectomy appear to have been variable or absent.Linner and Prijot,6 working with rabbits, concludedthat the reduced IOP during the day after extirpationof the superior cervical ganglion was due to reducedaqueous formation while outflow facility andepiscleral venous pressure remained constant. Thesefindings were confirmed by Lieb et al.'Langham and Taylor,8 although unable to obtain

consistent results working with cats, also reportedtransient reduction of IOP in rabbits followingganglionectomy. Further studies9 demonstrated thatthe reduced pressure was due to increased outflowfacility while aqueous production remained constant.These results were similar to those of Sears andBairany'° and Tomar and Agarwal. "It is still not clearwhether the reduced IOP in these animals is mediatedthrough alteration of aqueous production or outflowfacility. Potter'2 observed there is marked species

variation in the anatomy of the outflow tract includinginnervation and adrenoreceptor populations. Itseems prudent, therefore, to avoid drawing firm con-clusions about control of IOP in man from animalexperiments.

Clinical studies are mostly linked to the descriptionby the Swiss ophthalmologist Homer'3 of thecollection of physical signs which became known asHomer's syndrome. He described a patient withptosis, miosis, facial anhydrosis associated withflushing and temperature changes, reduced ipsilateralIOP (measured by tonometry), and enophthalmos. Itis now accepted that the enophthalmos is onlyapparent. "1Thompson'5 suggested that reduced IOP is a

transient sign of Homer's syndrome which cannot berelied upon in making a diagnosis. There are,however, reports of sustained reduction of IOPfollowing interruption of the cervical sympatheticsystem. Cobb and Scarlett'6 reported reduction ofIOP in the ipsilateral eye in 7 cases of Horner'ssyndrome while pressures were equal in an eighthcase. Davson and Matchett'7 alluded to clinicalstudies in man suggesting chronically lowered IOPfollowing stellectomy. Swegmark'8 studied aqueousdynamics in a patient with unilateral postganglionicHomer's syndrome. He showed that reduced IOP inthe ipsilateral eye was due to reduced aqueousproduction. By treatment with guanethidine drops(blocking release of noradrenaline at postganglionicnerve endings) he produced a comparable reductionof aqueous production in the normal eye. He con-cluded that sympathetic denervation reducedaqueous production and thus IOP. Similar findingswere subsequently reported by Langham andWeinstein'9 and Bron.20 Wentworth and Brubaker2'found a statistically significant reduction of IOP in 21cases of Homer's syndrome. Alteration of aqueousproduction in this series was not consistent.The concept of reducing IOP by alteration of the

sympathetic nerve supply to the eye has formed thebasis of both investigation and treatment ofglaucoma. Miller22 studied the effect of stellateganglion block with procaine on IOP. In patients withchronic simple glaucoma he reported an immediaterise in IOP followed by a fall to the original pressureor below during an hour. This change was thought tobe due to dilatation of intraocular capillaries. Thetreatment of chronic simple glaucoma by excision ofthe superior cervical ganglion was reported byAbadie23 and Jonnesco.24 It appears that the resultingimprovement in IOP was not sustained, and theprocedure was eventually abandoned. Many drugsnow in use for treating glaucoma act on ocularsympathetic mechanisms. They include adrenaline(mainly a-adrenergic receptor agonist), timolol (,3-

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adrenergic receptor blocker), and guanethidine.Their exact modes of action remain to a large extentobscure.The author has not located any reports of ocular

hypertension or glaucoma developing with pre-existing ocular sympathetic denervation.

PRESENT CASEThe reported patient has a right preganglionicHorner's syndrome. This is suggested by ptosis andmiosis, pupillary dilatation lag, pharmacologicalstudies, and the absence of facial sweating. On theleft side the situation is less clear. The relativeimmobility of the pupil makes interpretation of thepupillometric studies more difficult. However,preganglionic sympathetic denervation is stronglysuggested by pupillary dilatation lag, reduceddilatation to cocaine 10%, and absent facial sweating.The ptosis and miosis appear to have been relativelyless obvious on this side, and it is therefore difficult todescribe this clinical picture as Horner's syndrome.He undoubtedly has left ocular hypertension on the

basis of persistently elevated IOP in the presence ofvisual fields and optic discs which are within normallimits. The average left IOP untreated was 29-2mmHg; this was reduced by treatment to an average16-0 mmHg. The association of ocular sympatheticdenervation and ocular hypertension appears mostuncommon.The average IOP in the right eye was 9 0 mmHg.

Duke-Elder25 states that only 2% of the normalpopulation have pressures under 10 mmHg. This eyehas therefore maintained a pressure very much at thelower end of the normal range.

Outflow facilities were the same at 0-13 A.l mmHg-'min-' left eye and average 0-13 ,ul mmHg-' min-'right eye. These values also fall at the lower end ofwhat may be considered to be the normal range(0-12-0-57 ,ul mmHg-' min-').26 With similar outflowfacilities the most likely cause for asymmetry of IOP isa difference in rates of aqueous production. 9 While itis possible that the sympathetic denervation andocular hypertension are entirely independent, itseems reasonable to suggest that the relatively lowIOP in the right eye may be due to some protectiveeffect of the Homer's syndrome on that side. If so, ithas probably been mediated by alteration of aqueousproduction. This would be entirely consistent withthe quoted reports of reduced aqueous production inHorner's syndrome.There does not appear to be similar evidence that

the IOP rises as a result of ocular sympatheticdenervation in humans. It would certainly besurprising that this patient had maintained normaloptic discs and visual fields if his ocular hypertensiondated from cervical sympathectomy in 1953. It is

much more likely that the IOP has increased in recentyears in the presence of pre-existing sympatheticdenervation.The different behaviour of the 2 eyes might be

explained by the completeness of sympatheticdenervation that they have respectively suffered. Onthe right side the clinical and pharmacologicalevidence suggests a typical Homer's syndrome. Onthe left side 2 of the main features of Homer'ssyndrome, ptosis and miosis, were minimal or absent.Romano et al. 27 have drawn attention to variation inocular signs after upper dorsal sympathectomy,which is explained by variation either in nerve fibrepathways or by the degree of sympathetic injuryinflicted at surgery. It is possible that the reportedpatient has suffered a more complete sympathectomyon the right side. This asymmetry may have contri-buted to the maintenance of low normal IOP in theright eye while ocular hypertension has developed inthe left eye.

I thank Mr J. Shilling for permitting me to report this patient underhis care and Professor S. E. Smith. Department of Pharmacology, StThomas's Hospital, for performing the pupillometry and advising meon interpretation of the results.

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3 Zimmerman TJ. Harbin R, Pett M, Kaufman HE. Timololand facility of outflow. Invest Ophthalmol Visual Sci 1977; 16:623-4.

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