British Journal of Ophthalmology, 1979, 63, 832-836

Transient open-angle glaucoma associated withsickle cell trait: report of 4 cases

ALAN H. FRIEDMAN,'2 BARTON L. HALPERN,' DOROTHY N. FRIEDBERG,2FREDERICK M. WANG,2 AND STEVEN M. PODOSFrom the Departments of Ophthalmology of the 'Mount Sinai School of Medicine of the City University ofNew York and the 2Albert Einstein College of Medicine, Bronx, New York

SUMMARY Four black patients, all with sickle trait (SA), developed transient open-angle glaucomawith blood in Schlemm's canal. In 3 patients the condition followed blunt trauma, while in thefourth no antecedent trauma was described. The intraocular pressure became normal in all 4 caseswith the resolution of the haemorrhage from the trabecular meshwork and Schlemm's canal.

Sickle cell trait, the commonest of the sickle haemo-globinopathies, affects approximately 9% of theblack population of North America.' A variety ofocular abnormalities2-'2 have been reported to occurin patients with sickle cell trait. These have includedproliferative retinopathy, chorioretinal scarring,spontaneous vitreous haemorrhages, central retinalartery occlusion, angioid streaks, conjunctivalvascular abnormalities, and transient open-angleglaucoma. We herewith report 4 additional cases oftransient open-angle glaucoma which occurred inpatients with sickle trait. In 3 patients the glaucomafollowed blunt trauma with microscopic hyphaema,while in the fourth patient a microscopic haemor-rhage appeared in Schlemm's canal spontaneously.All patients had blood in the trabecular meshworkor the canal of Schlemm on gonioscopy, and theglaucoma resolved concomitantly with clearing ofblood from these areas.

Case reports

CASE 1A 53-year-old black woman had a history of 3episodes of blurred vision in the right eye associatedwith halos around lights for a 4-week period. Theseepisodes lasted several hours each and were notaccompanied by pain, injection, or other ocularsymptoms. The patient had hypertension of 8 years'duration, treated with methyldopa and a diuretic, andrheumatoid arthritis for several years, treated with

Requests for reprints to Sam Gartner, Library, AlbertEinstein College of Medicine/Montefiore Hospital andMedical Center, IlI East 210th Street, Bronx, New York10467, USA.

compound aspirin, phenacetin and caffeine tablets.There was no history of diabetes mellitus, glaucoma,ocular trauma, or other medical or ocular diseases.An ophthalmological examination 1 1 years pre-viously showed a corrected visual acuity of 20/25 ineach eye, applanation tension of 22 mmHg OU anda cup/disc ratio of025 in each eye.

Ophthalmological examination during the presentillness revealed a corrected visual acuity of 20/30OU. Applanation pressures were 42 mmHg OD and10 mmHg OS. Slit-lamp examination of the anteriorsegment was normal in both eyes. Gonioscopicexamination of the anterior chamber angle showed agrade III-IV open angle in both eyes, withoutrecession or neovascularisation. However, the righteye showed blood present in Schlemm's canal(7.00 to 11.00 o'clock), and a haemorrhage localisedto the trabecular meshwork from 7.00 to 8.00o'clock (Fig. 1). On ophthalmoscopic examinationcup/disc ratios of 0 45 OD and 0-15 OS were seen onstereoscopic examination at the slit-lamp. Outflowfacilities were 0-14 OD and 0-21 OS. Goldmannkinetic perimetry was normal in both eyes. Systemicblood pressure was 190 mmHg systolic and 110mmHg diastolic.

A complete blood count and sedimentation ratewere normal. Antinuclear antibody and latexfixation tests were negative. Haemoglobin electro-phoresis revealed an AS pattern. The 3-hour oralglucose tolerance test was abnormal: fasting bloodsugar 117 mg/100 ml (6-5 mmol/l); at 1 hour231 mg/100 ml (12-8 mmol/l); at 2 hours 166mg/100 ml (9-2 mmol/l); at 3 hours 88 mg/100 ml(4T9 mmol/p).The patient was treated with acetazolamide

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Transient open-angle glaucoma associated with sickle cell trait: report of 4 cases

Fig. 1 Goniophotograph ofcase1 showing blood in the canal ofSchlemm.

Fig. 2 Goniophotograph ofcase 3showing blood in the trabecularmeshwork.

250 mg orally 4 times a day and Epitrate (adrenalineacid tartrate) drops 2% OD twice a day. Over a2-week period the trabecular haemorrhage andblood in Schlemm's canal resolved. The intraocularpressure remained normal after medication wasdiscontinued and remained normal when the patientwas last examined 18 months later.

CASE 2A 9-year-old boy was struck in the left eye with astick 24 hours before admission to hospital. He

immediately developed a reduction in vision followedseveral hours later by pain in the eye and vomiting.Ocular examination showed the uncorrected visualacuity to be 20/20 OD and 20/200 OS. Applanationpressures were 10 mmHg OD and 40 mmHg OS.A superficial abrasion was present on the left uppereyelid. The left eye displayed moderateconjunctivalhyperaemia and mild microcystic corneal epithelialoedema. The anterior chamber of the right eye wasclear while the left eye had 3 + flare and cells (manyerythrocytes). No gross hyphaema was seen at the

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834 Alan H. Friedman, Barton L. Halpern, Dorothy N. Friedberg, Frederick M. Wang, and Steven M. Podos

slit-lamp. The pupillary reflex was brisk OD andsluggish OS. The vitreous and fundus were unre-markable. Gonioscopy of the left eye revealed bloodin Schlemm's canal.The patient was placed on bed rest, sedation, and

acetazolamide 125 mg by mouth 4 times daily.Examination next day showed an uncorrected visualacuity in the left eye of 20/20 with intraoculartension 36 mmHg. Gonioscopy showed blood layeredin the inferior portion of the anterior chamber angleand prominently in Schlemm's canal in the remainderof the angle. A sickle preparation was positive, andhaemoglobin electrophoresis revealed an AS pattern(Hgb A 56 %, Hgb S 44 %). All other laboratory testsincluding complete blood count, urine analysis,sequential multiple analyser (SMA) 6 and 12 werenormal. The haemorrhage cleared from the anteriorchamber over the next 5 days with return of intra-ocular pressure to normal levels. The acetazolamidewas discontinued without sequelae. The patient wasasymptomatic when examined 24 months later.

CASE 3A 23-year-old black man was struck in the right eye.He noticed a mild decrease in vision with pain in theeye. He was in excellent health otherwise. Ophthal-mological evaluation showed a best visual acuity of20/50 OD and 20/20 OS. The left eye was completelynormal. Applanation pressures were 30 mmHgOD and 14 mmHg OS. The right eye had 2 + bulbarhyperaemia, clear cornea with very fine cellulardeposits on the endothelium, 3 + aqueous flare, andcells (mostly erythrocytes). Gonioscopy revealed agrade 3 open angle OU with a dark red band ofblood in the trabecular meshwork OD (Fig. 2). Noperipheral anterior synechiae or recession of theanterior chamber angle were present. The pupillaryreactions, lens, vitreous, and fundus were normal.Tonography at this time revealed a facility of out-flow of 0-08 OD and 0-26 OS. The patient was put onacetazolamide 250 mg by mouth 4 times daily andprednisolone acetate 1 % eye drops 4 times daily.Haemoglobin electrophoresis revealed an AS

pattern (Hgb A 55 %, Hgb S 45 %). All other labora-tory studies, including complete blood count,urine analysis, SMA 6 and 12, and serum electro-phoresis were within normal limits.The blood cleared from Schlemm's canal 1 week

after admission with a concomitant return of intra-ocular tension to 16 mmHg. The visual acuityreturned to 20/20, but a repeat tonography showed acoefficient of outflow of 0 14 OD and 0-24 OS.Visual fields with tangent screen utilising a 3 mmwhite target at 1 m were normal in each eye. Allmedications were discontinued. The patient wasdischarged and lost to follow-up.

CASE 4The patient was a 34-year-old black man who waspunched in the left eye. When seen 2 days later thecorrected visual acuity was 20/20 OD and 20/100 OSIntraocular pressure was 16 mmHg OD and 36mmHg OS. The right eye was entirely normal. Theleft eye displayed 2 + bulbar hyperaemia andmoderate microcystic corneal oedema. The corneawas cleared with topical glycerin. No keratic precipi-tates were present. The anterior chamber revealed2+ aqueous flare and cells, many of which wereerythrocytes. Gonioscopy showed a grade 3 openangle, both eyes, and in the left eye a dense columnof dark red blood in Schlemm's canal. The pupillaryreactions were brisk OD and sluggish OS. Thelens, vitreous, and fundus appeared normal. Thepatient was placed on acetazolamide 250 mg bymouth 4 times daily and prednisolone acetate 1%drops 4 times daily. A complete laboratory examina-tion and haemoglobin electrophoresis revealedAS pattern (Hgb A 59%, Hgb S 41 %). The intra-ocular tension was unchanged over the next 24hours, and consequently the patient was givenoral glycerol 1-5 mg per kg. After 2 hours, theintraocular pressure was 22 mgHg in the left eye.Acetazolamide and glycerol were both required tocontrol the intraocular tension for the ensuing 6days. Examination at that time showed an intra-ocular pressure of 24 mmHg and blood in Schlemm'scanal. Glycerol was discontinued. Visual fieldsutilising a tangent screen at 1 m with a 2 mm whitetarget were full in both eyes. Tonography revealed afacility of outflow of 0-22 OD and 0 10 OS. Duringthe next 10 days the blood in Schlemm's canal wasgradually absorbed and the intraocular pressure was16 mmHg. Tonography at that time was 0-20 OD and0-20 OS. Ocular examination 18 months later wasentirely within normal limits.

Discussion

The severity of symptoms in patients with sickle-celltrait depends on several factors any of which mayincrease the amount of sickling. These factors13are: the percentage of S haemoglobin, oxygen ten-sion, pH, temperature, viscosity, vascular stasis,hyperkalaemia, increased carbon dioxide level, andpresence of reducing substances. Thus, as Shapiroand Baum12 observed, the consequence of smallnontraumatic (case 1) or traumatic hyphaemas(cases 2, 3, 4) in a patient may be transient open-angle glaucoma due to the incarceration of sicklederythrocytes in the canal of Schlemm and trabecularmeshwork.An erythrocyte can pass through vessels smaller

than its own diameter because of its ability to alter

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Transient open-angle glaucoma associated with sickle cell trait: report of4 cases

its own discoid shape. Thus the ease with whichnormal erythrocytes can negotiate the pathwaysthrough the trabecular meshwork, juxtacanaliculartissue, and into Schlemm's canal depends on theirextreme plasticity and easy deformability. Inomataand associates14 showed in the cynomolgus monkeythat normal erythrocytes measuring approximately6-7 ,um in diameter could pass through the endo-thelial trabeculae and enter the vacuoles of endo-thelial cells through 2-5-3-5 l±m pores by virtue ofthe erythrocyte's pliability. Erythrocytes then passfrom the vacuoles into the canal of Schlemm throughpores 1P0-1 8 ,um in diameter. Erythrocytes can alsopass through short pores 10 ,um in diameter in theflat portion of the trabecular endothelium into thecanal. In sickled erythrocytes13 the haemoglobinbecomes relatively insoluble and aggregates intolong polymers possessing a tubelike structure 20-22nm in diameter. Sickled erythrocytes are rigid andnonpliable and cannot pass through the trabecularmeshwork. Reduced erythrocyte deformability hasalso been observed in thalassaemia spherocytosisand, recently, in diabetes mellitus.15Presumably increased haemoglobin AIC (Hb AIC)

formed by the glycosylation of haemoglobin causesan increased intracellular viscosity and a concomi-tant decreased erythrocyte deformability.16 Gold-berg'7 in his study of 3 patients with sickle-cell traitwho sustained traumatic hyphaemas found that theyhad more sickling of erythrocytes in their aqueousthan in their peripheral venous blood. In consonancewith variations in haemoglobin S concentration inpatients with sickle trait Goldberg'7 observed that alower percentage of sickled erythrocytes was foundin the aqueous of the patients with lower concentra-tion of haemoglobin S. This observation is supportedby studies on the inhibitory effect of deoxygenatednormal haemoglobins (A or F) on the polymerisationof deoxygenated haemoglobin S.13 In all our cases itwould be difficult on the basis of clinical examinationto determine the exact site(s) of entrapment ofdeformed erythrocytes.

Patient 1 was at first thought to have had aglaucomatocyclitic crisis because of the recurrentblurring of vision, painless elevation of intraocularpressure, a white eye, open angles, normal visualfields, and intraocular pressure between attacks.'8The mild ocular hypertension (22mgHg OU) notedbefore the attacks and the cup/disc asymmetry areunusual in this entity, although a predilection forglaucomatocyclitic crisis in patients with primaryopen-angle glaucoma has been suggested.19 The lackof evidence of anterior chamber inflammation in thispatient on every examination, the persistence ofblood in the trabecular meshwork or in Schlemm'scanal, and the trabecular meshwork haemorrhage

are all atypical for glaucomatocyclitic crisis andmake this diagnosis untenable.Boniuk and Burton20 reported 2 cases of unilateral

glaucoma associated with sickle cell retinopathy.They postulated that the glaucoma was secondary toneovascularisation and peripheral anterior synechiaewithin the chamber angle which developed as asequel to intravascular sickling. None of ourpatients had sickle retinopathy, neovascularisation,or peripheral anterior synechiae.Haemorrhage into the trabecular meshwork is an

uncommon occurrence. Amsler and Verrey reportedobserving a haemorrhage in the anterior chamberangle following paracentesis in Fuchs's hetero-chromic iridocyclitis and considered it to be charac-teristic.21 Haemorrhage from Schlemm's canal hasbeen reported to have been induced by gonioscopyin these patients22 23 and in a few normal and glau-comatous eyes.24 However, none of our patients hadheterochromia iridis, as is typically seen in Fuchs'siridocyclitis.25 26 Trabecular haemorrhage has alsobeen observed in severe iridocyclitis,27 but none ofour patients had evidence of severe ocular inflamma-tion.The spontaneous reflux of blood into Schlemm's

canal may occasionally be seen in conditions thatproduce ocular hypotony or raised episcleral venouspressure.28 Increased episcleral venous pressure maybe produced by gonioscopy and by inflating a bloodpressure cuff about the neck. Either manoeuvre mayproduce obstruction of blood flow through thejugular veins. Sickle-cell disease, hypertension,rheumatoid arthritis, and diabetes mellitus are allassociated with small-vessel disease, which may beassociated with episcleral venous obstruction andstasis and lead to sickling of blood that has spon-taneously refluxed into Schlemm's canal. Cogan andcoworkers reported that in diabetes mellitus patientsmay have an elevated serum viscosity.29 Coupledwith an increased intracellular viscosity due toglycosylation and decreased erythrocyte deforma-bility,'5 16 these may also predispose to venous stasisand sickling.The treatment of what may hitherto have been

described as 'insignificant' hyphaemas in blacksmust be re-evaluated. All blacks with hyphaemasshould have sickle screening tests and haemoglobinelectrophoresis. Because of the effects of increasedintraocular pressure in reducing perfusion to theretina and optic nerve in patients with sickle trait,extreme care must be undertaken in monitoring theintraocular pressure.7 9 The ophthalmologist mustbe judicious in the use of carbonic anhydrase inhi-bitors and osmotic therapy. Increased serum tonicityafter diuretic and osmotic therapy in associationwith vascular stasis coincident with increased

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836 Alan H. Friedman, Barton L. Halpern, Dorothy N. Friedberg, Frederick M. Wang, and Steven M. Podos

intraocular pressure may precipitate vascular occlu-sions in patients with sickle-cell trait." And, asGoldbergl7 30 has suggested, early anteriorchamberparacentesis may be the most efficacious method ofremoving sickled erythrocytes from the anteriorchamber.

We are grateful to Mr Henrick Malpica and Mr RobertCampanile for the photography and to Mrs Stemma Askinazifor typing the manuscript.This work was supported in part by National Eye Institutegrants EY 01876 and EY 00613 and an unrestricted grantfrom Research to Prevent Blindness, Inc.

References

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