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Home , Blurred vision, Sickle cell retinopathy

Br J Ophthalmol: first published as 10.1136/bjo.63.12.832 on 1 December 1979. Downloaded from British Journal of , 1979, 63, 832-836

Transient open-angle associated with sickle cell trait: report of 4 cases ALAN H. FRIEDMAN,'2 BARTON L. HALPERN,' DOROTHY N. FRIEDBERG,2 FREDERICK M. WANG,2 AND STEVEN M. PODOS From the Departments of Ophthalmology of the 'Mount Sinai School of Medicine of the City University of New York and the 2Albert Einstein College ofMedicine, Bronx, New York

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

Sickle cell trait, the commonest of the sickle haemo- compound aspirin, phenacetin and caffeine tablets. globinopathies, affects approximately 9 % of the There was no history of mellitus, glaucoma, black population of North America.' A variety of ocular trauma, or other medical or ocular diseases. ocular abnormalities2-'2 have been reported to occur An ophthalmological examination 1 1 years pre- in patients with sickle cell trait. These have included viously showed a corrected visual acuity of 20/25 in proliferative , chorioretinal scarring, each eye, applanation tension of 22 mmHg OU and copyright. spontaneous vitreous haemorrhages, central retinal a cup/disc ratio of025 in each eye. artery occlusion, , conjunctival Ophthalmological examination during the present vascular abnormalities, and transient open-angle illness revealed a corrected visual acuity of 20/30 glaucoma. We herewith report 4 additional cases of OU. Applanation pressures were 42 mmHg OD and transient open-angle glaucoma which occurred in 10 mmHg OS. Slit-lamp examination of the anterior patients with sickle trait. In 3 patients the glaucoma segment was normal in both eyes. Gonioscopic followed blunt trauma with microscopic hyphaema, examination of the anterior chamber angle showed a while in the fourth patient a microscopic haemor- grade III-IV open angle in both eyes, without rhage appeared in Schlemm's canal spontaneously. recession or neovascularisation. However, the right http://bjo.bmj.com/ All patients had blood in the trabecular meshwork eye showed blood present in Schlemm's canal or the canal of Schlemm on gonioscopy, and the (7.00 to 11.00 o'clock), and a haemorrhage localised glaucoma resolved concomitantly with clearing of to the trabecular meshwork from 7.00 to 8.00 blood from these areas. o'clock (Fig. 1). On ophthalmoscopic examination cup/disc ratios of 0 45 OD and 0-15 OS were seen on Case reports stereoscopic examination at the slit-lamp. Outflow facilities were 0-14 OD and 0-21 OS. Goldmann on October 2, 2021 by guest. Protected CASE 1 kinetic perimetry was normal in both eyes. Systemic A 53-year-old black woman had a history of 3 blood pressure was 190 mmHg systolic and 110 episodes of in the right eye associated mmHg diastolic. with halos around lights for a 4-week period. These A complete blood count and sedimentation rate episodes lasted several hours each and were not were normal. Antinuclear antibody and latex accompanied by pain, injection, or other ocular fixation tests were negative. Haemoglobin electro- symptoms. The patient had of 8 years' phoresis revealed an AS pattern. The 3-hour oral duration, treated with methyldopa and a diuretic, and glucose tolerance test was abnormal: fasting blood rheumatoid arthritis for several years, treated with sugar 117 mg/100 ml (6-5 mmol/l); at 1 hour 231 mg/100 ml (12-8 mmol/l); at 2 hours 166 Requests for reprints to Sam Gartner, Library, Albert ml 88 ml Einstein College of Medicine/Montefiore Hospital and mg/100 (9-2 mmol/l); at 3 hours mg/100 Medical Center, IlI East 210th Street, Bronx, New York (4T9 mmol/p). 10467, USA. The patient was treated with acetazolamide 832 Br J Ophthalmol: first published as 10.1136/bjo.63.12.832 on 1 December 1979. Downloaded from Transient open-angle glaucoma associated with sickle cell trait: report of4 cases 833

Fig. 1 Goniophotograph ofcase 1 showing blood in the canal of Schlemm. copyright.

Fig. 2 Goniophotograph ofcase 3 showing blood in the trabecular meshwork. http://bjo.bmj.com/ on October 2, 2021 by guest. Protected

250 mg orally 4 times a day and Epitrate (adrenaline immediately developed a reduction in vision followed acid tartrate) drops 2% OD twice a day. Over a several hours later by pain in the eye and vomiting. 2-week period the trabecular haemorrhage and Ocular examination showed the uncorrected visual blood in Schlemm's canal resolved. The intraocular acuity to be 20/20 OD and 20/200 OS. Applanation pressure remained normal after medication was pressures were 10 mmHg OD and 40 mmHg OS. discontinued and remained normal when the patient A superficial abrasion was present on the left upper was last examined 18 months later. . The left eye displayed moderateconjunctival hyperaemia and mild microcystic corneal epithelial CASE 2 oedema. The anterior chamber of the right eye was A 9-year-old boy was struck in the left eye with a clear while the left eye had 3 + flare and cells (many stick 24 hours before admission to hospital. He erythrocytes). No gross hyphaema was seen at the Br J Ophthalmol: first published as 10.1136/bjo.63.12.832 on 1 December 1979. Downloaded from 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 and CASE 4 sluggish OS. The vitreous and fundus were unre- The patient was a 34-year-old black man who was markable. Gonioscopy of the left eye revealed blood punched in the left eye. When seen 2 days later the in Schlemm's canal. corrected visual acuity was 20/20 OD and 20/100 OS The patient was placed on bed rest, sedation, and Intraocular pressure was 16 mmHg OD and 36 acetazolamide 125 mg by mouth 4 times daily. mmHg OS. The right eye was entirely normal. The Examination next day showed an uncorrected visual left eye displayed 2 + bulbar hyperaemia and acuity in the left eye of 20/20 with intraocular moderate microcystic corneal oedema. The tension 36 mmHg. Gonioscopy showed blood layered was cleared with topical glycerin. No keratic precipi- in the inferior portion of the anterior chamber angle tates were present. The anterior chamber revealed and prominently in Schlemm's canal in the remainder 2+ aqueous flare and cells, many of which were of the angle. A sickle preparation was positive, and erythrocytes. Gonioscopy showed a grade 3 open haemoglobin electrophoresis revealed an AS pattern angle, both eyes, and in the left eye a dense column (Hgb A 56 %, Hgb S 44 %). All other laboratory tests of dark red blood in Schlemm's canal. The pupillary including complete blood count, urine analysis, reactions were brisk OD and sluggish OS. The sequential multiple analyser (SMA) 6 and 12 were , vitreous, and fundus appeared normal. The normal. The haemorrhage cleared from the anterior patient was placed on acetazolamide 250 mg by chamber over the next 5 days with return of intra- mouth 4 times daily and prednisolone acetate 1 % ocular pressure to normal levels. The acetazolamide drops 4 times daily. A complete laboratory examina- was discontinued without sequelae. The patient was tion and haemoglobin electrophoresis revealed asymptomatic when examined 24 months later. AS pattern (Hgb A 59%, Hgb S 41 %). The intra- ocular tension was unchanged over the next 24 CASE 3 hours, and consequently the patient was given A 23-year-old black man was struck in the right eye. oral glycerol 1-5 mg per kg. After 2 hours, the He noticed a mild decrease in vision with pain in the intraocular pressure was 22 mgHg in the left eye. eye. He was in excellent health otherwise. Ophthal- Acetazolamide and glycerol were both required to mological evaluation showed a best visual acuity of control the intraocular tension for the ensuing 6 copyright. 20/50 OD and 20/20 OS. The left eye was completely days. Examination at that time showed an intra- normal. Applanation pressures were 30 mmHg ocular pressure of 24 mmHg and blood in Schlemm's OD and 14 mmHg OS. The right eye had 2 + bulbar canal. Glycerol was discontinued. Visual fields hyperaemia, clear cornea with very fine cellular utilising a tangent screen at 1 m with a 2 mm white deposits on the endothelium, 3 + aqueous flare, and target were full in both eyes. Tonography revealed a cells (mostly erythrocytes). Gonioscopy revealed a facility of outflow of 0-22 OD and 0 10 OS. During grade 3 open angle OU with a dark red band of the next 10 days the blood in Schlemm's canal was blood in the trabecular meshwork OD (Fig. 2). No gradually absorbed and the intraocular pressure was peripheral anterior synechiae or recession of the 16 mmHg. Tonography at that time was 0-20 OD and http://bjo.bmj.com/ anterior chamber angle were present. The pupillary 0-20 OS. Ocular examination 18 months later was reactions, lens, vitreous, and fundus were normal. entirely within normal limits. Tonography at this time revealed a facility of out- flow of 0-08 OD and 0-26 OS. The patient was put on Discussion acetazolamide 250 mg by mouth 4 times daily and prednisolone acetate 1 % eye drops 4 times daily. The severity of symptoms in patients with sickle-cell Haemoglobin electrophoresis revealed an AS trait depends on several factors any of which may pattern (Hgb A 55 %, Hgb S 45 %). All other labora- increase the amount of sickling. These factors13 on October 2, 2021 by guest. Protected tory studies, including complete blood count, are: the percentage of S haemoglobin, oxygen ten- urine analysis, SMA 6 and 12, and serum electro- sion, pH, temperature, viscosity, vascular stasis, phoresis were within normal limits. hyperkalaemia, increased carbon dioxide level, and The blood cleared from Schlemm's canal 1 week presence of reducing substances. Thus, as Shapiro after admission with a concomitant return of intra- and Baum12 observed, the consequence of small ocular tension to 16 mmHg. The visual acuity nontraumatic (case 1) or traumatic hyphaemas returned to 20/20, but a repeat tonography showed a (cases 2, 3, 4) in a patient may be transient open- coefficient of outflow of 0 14 OD and 0-24 OS. angle glaucoma due to the incarceration of sickled Visual fields with tangent screen utilising a 3 mm erythrocytes in the canal of Schlemm and trabecular white target at 1 m were normal in each eye. All meshwork. medications were discontinued. The patient was An erythrocyte can pass through vessels smaller discharged and lost to follow-up. than its own diameter because of its ability to alter Br J Ophthalmol: first published as 10.1136/bjo.63.12.832 on 1 December 1979. Downloaded from Transient open-angle glaucoma associated with sickle cell trait: report of4 cases 835 its own discoid shape. Thus the ease with which are all atypical for glaucomatocyclitic crisis and normal erythrocytes can negotiate the pathways make this diagnosis untenable. through the trabecular meshwork, juxtacanalicular Boniuk and Burton20 reported 2 cases of unilateral tissue, and into Schlemm's canal depends on their glaucoma associated with . extreme plasticity and easy deformability. Inomata They postulated that the glaucoma was secondary to and associates14 showed in the cynomolgus monkey neovascularisation and peripheral anterior synechiae that normal erythrocytes measuring approximately within the chamber angle which developed as a 6-7 ,um in diameter could pass through the endo- sequel to intravascular sickling. None of our thelial trabeculae and enter the vacuoles of endo- patients had sickle retinopathy, neovascularisation, thelial cells through 2-5-3-5 l±m pores by virtue of or peripheral anterior synechiae. the erythrocyte's pliability. Erythrocytes then pass Haemorrhage into the trabecular meshwork is an from the vacuoles into the canal of Schlemm through uncommon occurrence. Amsler and Verrey reported pores 1P0-1 8 ,um in diameter. Erythrocytes can also observing a haemorrhage in the anterior chamber pass through short pores 10 ,um in diameter in the angle following paracentesis in Fuchs's hetero- flat portion of the trabecular endothelium into the chromic iridocyclitis and considered it to be charac- canal. In sickled erythrocytes13 the haemoglobin teristic.21 Haemorrhage from Schlemm's canal has becomes relatively insoluble and aggregates into been reported to have been induced by gonioscopy long polymers possessing a tubelike structure 20-22 in these patients22 23 and in a few normal and glau- nm in diameter. Sickled erythrocytes are rigid and comatous eyes.24 However, none of our patients had nonpliable and cannot pass through the trabecular heterochromia iridis, as is typically seen in Fuchs's meshwork. Reduced erythrocyte deformability has iridocyclitis.25 26 Trabecular haemorrhage has also also been observed in thalassaemia spherocytosis been observed in severe iridocyclitis,27 but none of and, recently, in diabetes mellitus.15 our patients had evidence of severe ocular inflamma- Presumably increased haemoglobin AIC (Hb AIC) tion. formed by the glycosylation of haemoglobin causes The spontaneous reflux of blood into Schlemm's an increased intracellular viscosity and a concomi- canal may occasionally be seen in conditions that tant decreased erythrocyte deformability.16 Gold- produce ocular hypotony or raised episcleral venous copyright. berg'7 in his study of 3 patients with sickle-cell trait pressure.28 Increased episcleral venous pressure may who sustained traumatic hyphaemas found that they be produced by gonioscopy and by inflating a blood had more sickling of erythrocytes in their aqueous pressure cuff about the neck. Either manoeuvre may than in their peripheral venous blood. In consonance produce obstruction of blood flow through the with variations in haemoglobin S concentration in jugular veins. Sickle-cell disease, hypertension, patients with sickle trait Goldberg'7 observed that a rheumatoid arthritis, and diabetes mellitus are all lower percentage of sickled erythrocytes was found associated with small-vessel disease, which may be in the aqueous of the patients with lower concentra- associated with episcleral venous obstruction and tion of haemoglobin S. This observation is supported stasis and lead to sickling of blood that has spon- http://bjo.bmj.com/ by studies on the inhibitory effect of deoxygenated taneously refluxed into Schlemm's canal. Cogan and normal haemoglobins (A or F) on the polymerisation coworkers reported that in diabetes mellitus patients of deoxygenated haemoglobin S.13 In all our cases it may have an elevated serum viscosity.29 Coupled would be difficult on the basis of clinical examination with an increased intracellular viscosity due to to determine the exact site(s) of entrapment of glycosylation and decreased erythrocyte deforma- deformed erythrocytes. bility,'5 16 these may also predispose to venous stasis

Patient 1 was at first thought to have had a and sickling. on October 2, 2021 by guest. Protected glaucomatocyclitic crisis because of the recurrent The treatment of what may hitherto have been blurring of vision, painless elevation of intraocular described as 'insignificant' hyphaemas in blacks pressure, a white eye, open angles, normal visual must be re-evaluated. All blacks with hyphaemas fields, and intraocular pressure between attacks.'8 should have sickle screening tests and haemoglobin The mild (22mgHg OU) noted electrophoresis. Because of the effects of increased before the attacks and the cup/disc asymmetry are intraocular pressure in reducing perfusion to the unusual in this entity, although a predilection for and in patients with sickle trait, glaucomatocyclitic crisis in patients with primary extreme care must be undertaken in monitoring the open-angle glaucoma has been suggested.19 The lack intraocular pressure.7 9 The ophthalmologist must of evidence of anterior chamber in this be judicious in the use of carbonic anhydrase inhi- patient on every examination, the persistence of bitors and osmotic therapy. Increased serum tonicity blood in the trabecular meshwork or in Schlemm's after diuretic and osmotic therapy in association canal, and the trabecular meshwork haemorrhage with vascular stasis coincident with increased Br J Ophthalmol: first published as 10.1136/bjo.63.12.832 on 1 December 1979. Downloaded from 836 Alan H. Friedman, Barton L. Halpern, Dorothy N. Friedberg, Frederick M. Wang, and Steven M. Podos intraocular pressure may precipitate vascular occlu- lInomata H, Bill A, Smelser G. Aqueous humor pathways through the travecular meshwork and into Schlemm's sions in patients with sickle-cell trait." And, as canal in the cynomolgus monkey (Macacca irus): An Goldbergl7 30 has suggested, early anteriorchamber electron microscopic study. Am J Ophthalmol 1972; paracentesis may be the most efficacious method of 73:760-789. removing sickled erythrocytes from the anterior "McMillan DE, Utterback NG, LaPuma S. Reduced erythrocyte deformability in diabetes. Diabetes 1978; chamber. 27:895-900. '6Bunn HF, Gabbay KH, Gallop PM. The glycosylation of We are grateful to Mr Henrick Malpica and Mr Robert hemoglobin: Relevance in diabetes mellitus. Science Campanile for the photography and to Mrs Stemma Askinazi 1978; 200:21-27. for typing the manuscript. 7Goldberg MF. The diagnosis and treatment of sickled This work was supported in part by National Eye Institute erythrocytes in human hyphemas. Trans Am Ophthalmol grants EY 01876 and EY 00613 and an unrestricted grant Soc in press. from Research to Prevent Blindness, Inc. "Posner A, Schlossman A. Syndrome of unilateral recurrent attacks of glaucoma with cyclitic symptoms. Arch Ophthal- References mol 1948; 39:517-535. 9Kass MA, Baker B, Kolker AE. Glaucomatocyclitic crisis 'Kennedy JJ, Cope CB. Intraocular lesions associated and primary open-angle glaucoma. Am J Ophthalmol with sickle-cell disease. Arch Ophthalmol 1957; 58:163-168. 1973; 75:668-673. 2Nagpal KC, Asdourian GK, Patrianakos D et al. Pro- "OBoniuk M, Burton GL. Unilateral glaucoma with sickel- liferative retinopathy in sickle cell trait. Report of seven cell retinopathy. Trans Am Acad Ophthalmol Otolaryngol cases. Arch Intern Med 1977; 137:325-328. 1964; 68:316-328. 3Isbey EK, Clifford GO, Tanaka KR. "Amsler M, Verrey F. 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Retinal arterial occlusion 25Loewenfeld IE, Thompson HS. Fuchs' heterochromic following ocular trauma in youths with sickle-trait hemo- cyclitis. A critical review of the literature. I. Clinical globinopathy. Am J Ophthalmol 1972; 74:494-497. characteristics of the syndrome. Surv Ophthalmol 1972; 8Gerde LS. Angioid streaks in sickle-cell trait hemoglobino- 17:394-457. pathy. Am J Ophthalmol 1974; 77:462-471. 26Loewenfeld IE, Thompson HS. Fuchs' heterochromic 9Sorr EM, Goldberg RE. Traumatic CRA and with sickle- cyclitis. A critical review of the literature. II. Etiology and cell trait. Am J Ophthalmol 1975; 80:648-652. mechanisms. Surv Ophthalmol 1973; 18:2-61. "Finelli PJ. Sickle-cell trait and transient monocular blind- 27Busacca A. Elements de Gonioscopie. Sao Paulo: Tipo- ness. Am J Ophthalmol 1976; 81:850-851. graphia Rossolillo, 1945. "Radius RL, Finkelstein D. Central retinal artery occlusion 28Phelps CD, Asseff CF, Weisman RL, Podos SM, Becker (reversible) in sickle trait with glaucoma. Br J Ophthalmol B. Blood reflux into Schlemm's canal. Arch Ophthalmol

1976; 60:428-430. 1972; 88:625-631. http://bjo.bmj.com/ "Shapiro AL, Baum JL. Acute open-angle glaucoma in a 29Cogan DG, Merola L, Laibson PR. Blood viscosity, serum patient with sickle-cell trait. Am J Ophthalmol 1964; hexosamine and . Diabetes 1961; 58:292-294. 10:393-395. 3Dean J, Schechler AN. Sickle-cell anemia: Molecular 3"Goldberg MF. The diagnosis and treatment of secondary and cellular bases of therapeutic approaches. N Engl JI glaucoma after in sickle cell patients. Amer J Med 1978; 299:753, 804-811, 863-870. Ophthalmol 1979; 87:43-49. on October 2, 2021 by guest. Protected