Br J Ophthalmol: first published as 10.1136/bjo.60.5.361 on 1 May 1976. Downloaded from

Brit. Y. Ophthal. (1976) 6o, 36I

Ocular findings in elderly cases of homozygous sickle-cell disease in Jamaica

P. I. CONDON* AND G. R. SERJEANT From the MRC Laboratories (Jamaica), University of the West Indies, Kingston, Jamaica

Sickle-cell disease is characterized by recurrent one each, and was unknown in five patients. vascular occlusive episodes and a progressive Traumatic causes were more common in younger obliteration of capillary beds. This process can patients and more common in be directly observed in the eye and its occurrence the older group. in the peripheral has been well documented Tortuosity of the major retinal vessels was (Welch and Goldberg, I966; Goldberg, 1971; present in i8 (30 per cent) patients affecting the Condon and Serjeant, I972a, b, c). The effects of veins alone in 13 and the arteries and veins in five. such thrombotic episodes might be expected to Peripheral retinal vessel disease was classified as accumulate with age and to be most marked in previously described (Condon and Serjeant, I972a) elderly patients. The results of ocular examinations into three grades. Grade I consisted of narrowing in 6o patients aged over 40 years with homozygous of peripheral arterioles with tortuosity and abnormal sickle-cell (SS) disease in Jamaica are presented looping of peripheral venules. Grade II included below. tortuosity, dilatation, and microaneurysmal for- mation in the peripheral capillary network; coarsen- Patients and methods ing of the network with loss of some fine vessels; and abnormal branching of peripheral venules. The patients attended the sickle-cell clinic of the Grade III changes were arteriolar occlusions. The http://bjo.bmj.com/ University Hospital of the West Indies. Ocular exami- grade of vessel disease was usually identical in both nation of 56 out of 66 patients aged over 40 years eyes (37 patients), although differences between (born before i January 1935) attending the clinic was possible. In addition, the cases of four patients (cases eyes of one grade (I2 patients) or even two grades 2, 31, 47, 54) aged over 40 years at the time of previous (six patients) did occur. Grade I changes were examinations, but who had since died, were studied. present in 40 eyes, grade II in 21, and grade III in The overall group therefore consisted of 6o patients 40. The peripheral retinal vessels appeared normal (27 men, 33 women) whose ages ranged from 40-66 in I 5 eyes. Arterio-venous fistulae occurred in on September 30, 2021 by guest. Protected copyright. years. four eyes (four patients) and was associated with Homozygous sickle-cell disease was diagnosed on grade III vessel disease in all cases. criteria reported elsewhere (Serjeant, I974). Methods of proliferans occurred in 12 eyes (eight patients), the ocular examination have been previously described lesions being often multiple and affecting large (Condon and Serjeant, I972a). Retinitis proliferans and were confirmed in each case by fluores- areas of the peripheral retina. In four of the eight cein angiography. patients the lesions had fibrosed, presumably after spontaneous vessel occlusion. In order to assess the effect of age on peripheral Results retinal vessel disease and retinitis proliferans the The findings are summarized in Table I. Visual group was divided into those aged 45 years or acuity was decreased in 40 eyes (25 patients) and under (29 patients) and those aged 46 years or was 6/6o or less in eight eyes (eight patients). The over (31 patients). The results are summarized in causes included astigmatic refractive errors in Table II, which shows that mild grades of vessel four patients, trauma in three, disease (I and II) were more common in the in two, macular degeneration of unknown origin younger groups and that the more severe grade III in seven, a toxoplasma lesion, long-standing optic and retinitis proliferans predominated in the older atrophy, , and vitreous haemorrhage in group. Women also seemed to have more normal retinal vasculature and accounted for 5/7 (7I per *Present address: Regional Eye Department, Ardkeen Hospital, cent) patients with normal vessels and I2/14 Waterford, Ireland (86 per cent) of those with grade I vessel disease. Address for reprints: Ardkeen Hospital, Waterford, Ireland Chorioretinal scars known as 'sunburst' spots El Br J Ophthalmol: first published as 10.1136/bjo.60.5.361 on 1 May 1976. Downloaded from

362 British Journal of

Table I Octular findings in 6o patients aged 40 or over with homnozygous sickle-cell disease. Arabic figures refer to number of lesions in eye. See text Jor criteria for grading retinal vessel disease Tortuous Grade of Chorio- Micro- major retinal Arterio- retinal aneurysms Visual retinal vessel venous Retinitis sunburst of posterior Angioid Age acuity vessels disease fistulae proliferans lesions pole streaks Comments Case and (A =arterial, no. sex R L V = venous) R L R L R L R L R L R L

40 M 6/6 6/6 - II II - - - - 2 - - - - 2S 40 M 6/6 6/6o - II rr- - - (L) long-standing optic atrophy 3 40 F 6/6 6/6 V I I -- - 4 4I M 6/6 6/6 - III I -- - 5 4I M 6/6 6/6 AV If II -- - 6 4I M 6/6 I/6o V III -* - * - Traumatic 7 4I M 6/6 6/6 - 8 4I F 6/6 6/6 - 9 42 M HM 6/6 V -* IrI -* - - Traumatic lesion (R) eye I0 42 M 6/6 6/6 V I I - - I I 42 M 6/6 6/6 V III II - 12 42 F 6/6 6/6 - I III -- - I3 42 F 6/9 6/I2 - I i-- - - Myopic I4 42 F 6/6 6/6 - I III -- - 3- I I5 42 F 6/6 6/6 - II I -- -- i6 43 M 6/6 6/6 - - II

I7 43 M 6/6 6/6 - II1 III - - - - I -.- I8 43 M 6/i8 6/24 - II III - - I9 43 M 6/36 6/6 - + + Healed toxoplasma lesion (R) macula 20 43 M 6/6 6/6 - II II - - I 4- + 2I 43 F 6/6 6/6 V I I -- - 22 44 F 6/6 6/6 - I I-- 23 44 F 6/6 6/6 V I I -- - 24 44 F 6/6 CF - I I -- - Traumatic lesion (L) eye 25 44 F 6/6 6/6 V III III -- 2 - I 26 44 F 6/6 6/6 - 27 45 F 6/6 6/6 - III II -- - - 28 45 M 6/6 6/6 I - - +-i.- http://bjo.bmj.com/ 29 45 F 6/6 6/9 V I I - - Macular degeneration -4- 30 46 M 6/I2 6/I2 - III III - - I + 3I 46 M 6/6 6/6 - II I -- - 32 46 F 6/I2 6/6 - II r - - I I - Macular degeneration 33 46 F 6/6 6/6 - 1 I - - 34 47 M 6/I2 6/I2 V I1 I - - Macular degeneration 35 47 F 6/6 6/6 - II 1II - - 36 48 M 6/I2 6/9 - III I - - I I 37 48 F 6/9 6/9 - I I- - 38 49 M 6/6 6/6 - 1II iii -- - 9 3 on September 30, 2021 by guest. Protected copyright. 39 49 M 6/6 6/6 - III III - 2 1 40 49 M 6/6 6/6 - I III - - 4I 49 F 6/6 6/6 - I I -- - 42 49 F 6/6 6/6 AV 43 49 F 6/i8 6/I8 - I I - - - Macular degeneration -* -* 44 50 M Nil 6/I2 - III -* I -* 3 -* I 4. - ?Retinal detachment (R) 45 53 M 6/6 6/6 V II I - - + 46 53 F 6/9 6/9 - - 2 47 53 F 6/I8 6/I2 - 1I IHI - - I - Macular degeneration 48 ss F 6/I2 6/I2 V II I - - - Myopic astigmatism 49 55 F 6/6 6/6 - I I - - so 56 F 6/6 6/24 AV III III - - 2 3 - (L) perimacular fibrosis from vitreous haemorrhage 50 57 F 6/6 6/6 - 52 58 F 6/24 6/6 - III III F--+ + F 53 59 6/6 Nil - III -. - -* 6 -s - -s - -+ - -, Retinal detachment (L) 54 59 F 6/36 2/6o - r III --. - Senile macular degener- ation and cataracts 55 59 F 6/I2 6/24 AV III III ------+ (L) vitreous haemorrhage 56 6o M 6/6 6/6 - III III.--± 57 6o F 6/36 6/24 AV + Macular degeneration 58 6o F 6/6 6/6 - - 59 6i F 6/36 6/6o - Senile cataracts 6o 66 M 6/6 6/6 V III III. *Inapplicable: peripheral retina could not be seen Severity of lesion: +, ++, +++ Br J Ophthalmol: first published as 10.1136/bjo.60.5.361 on 1 May 1976. Downloaded from Homozygous sickle-cell disease 363

Table II Age distribution of peripheral retinal vessel disease and retinitis proliferans

Eyes affected Grade of vessel disease Age Eyes Normal - ---. (years) No. observed* vessels I II III RP No. Percentage No. Percentage No. Percentage No. Percentage No. Percentage

40-45 29 56 7 12 22 38 13 22 14 24 I 2 46-60 31 6o 8 13 I8 29 8 I3 26 42 7 II *Excludes four eyes in which assessment of the peripheral retina was impossible

occurred in 2o eyes (i6 patients). Microaneurysms are presumed to precede the development of at the posterior pole were seen in 12 eyes (nine retinitis proliferans, occurred mainly in the youn- patients). Angioid streaks occurred in 25 eyes ger patients, whereas retinitis proliferans (RP) was (I3 patients). They were bilateral in IZ patients, in almost confined to older patients of the series. The i i of whom they were better developed on the relatively high prevalence of RP in patients over right side. They occurred in 4/29 (14 per cent) the age of 50 (29 per cent) is of especial interest patients aged 45 years and under compared to since this has been considered un- 9/33 (27 per cent) patients over this age. In one common in other series of patients with SS disease case (Case 20) angioid streaks developed over a (Henry and Chapman, I954; Lieb and others, four-year period of observation between ages I959; Welch and Goldberg, I966). In an earlier 39-43. In another patient (Case 57) bilateral series that included Jamaican patients of all ages macular degeneration and reduced visual acuity Condon and Serjeant (0972a) found this complica- occurred concurrently with early angioid streaks tion in only 2/76 (3 per cent) patients, one aged around the disc, but 34 and the other aged 55 (case 53 in present suggested that these lesions were probably unasso- report). Since RP seems to be age-related, some ciated. Clinical evidence of pseudoxanthoma elasti- variation in prevalence may reflect different age cum was not present in any patient with angioid structures of other series. It was of interest that streaks. in 4/8 patients areas of retinitis proliferans had http://bjo.bmj.com/ become spontaneously occluded and the vessels no longer leaked fluorescein on angiography. Discussion Although spontaneous obliteration of new vessels Tortuosity of the major retinal veins has been constitutes a progression of vascular disease in reported in homozygous sickle-cell disease in pathological terms, such a process would tend to between I0-96 per cent of cases (Klinefelter, halt the progressive nature of peripheral retinal

I942; Henry and Chapman, 1954; Smith and ischaemia and render less likely complications such on September 30, 2021 by guest. Protected copyright. Conley, I954; Hannon, 1956; Hook and Cooper, as vitreous haemorrhage and retinal detachment. 1958; Lieb, Geeraets, and Guerry, I959; Welch The aetiology of pigmented chorioretinal lesions, and Goldberg, I966). Condon and Serjeant or 'sunburst' spots, is unknown although they may (1972a) noted this finding in 8/76 (ii per cent) result from retinal or choroidal infarcts. This patients with SS disease in an earlier report and concept was supported by the presence of these in I8/6o (30 per cent) of the present series. The lesions in II/40 (28 per cent) eyes with grade III variable prevalence of this sign may reflect real vessel disease compared with 9/76 (I2 per cent) differences in populations or may result from the with milder grades of vessel disease. subjective nature of tortuosity. Interpretation of Tortuosity and dilatation of the capillary net- this finding is further complicated by lack of valid work with microaneurysmal formation at the control data. However, the available evidence posterior pole was noted by Lieb and others suggests that tortuosity of the major retinal veins (1959) and reported in 30/76 (40 per cent) patients is associated with sickle-cell disease. Tortuosity of with SS disease in Jamaica (Condon and Serjeant, both arteries and veins may indicate an indepen- I972a). This finding appears more characteristic of dently inherited genetically determined abnor- homozygous sickle cell disease than of other mality which can also coincide with sickle-cell variants such as sickle-cell-haemoglobin C disease disease (Condon and Serjeant, 1972a). and sickle-cell-5 thalassaemia (Condon and Serjeant, Although the severity of peripheral retinal 1972b, c), and it is tempting to postulate that they vessel disease generally increased with age, some are a retinal equivalent to the abnormal dilatations elderly patients still manifested normal vessels or often seen in the conjunctival capillary bed very mild changes. Arterio-venous fistulae, which (Serjeant, Condon, and Serjeant, I972). Br J Ophthalmol: first published as 10.1136/bjo.60.5.361 on 1 May 1976. Downloaded from 364 British Yournal of Ophthalmology

Angioid streaks are a recognized feature of evidence of angioid streaks (Condon, Serjeant, sickle-cell , although case reports are and Ikeda, I973). The clinical course of angioid limited to a few patients. Paton (I959) and Lieb streaks in sickle-cell disease seems more benign and others (I959) each described two cases with SS than when associated with other conditions. No disease. Geeraets and Guerry (I960) reported five associated haemorrhages or exudates were seen in cases, three with probable SS disease and two with the present group, and in the one case with macular SC disease. Suerig and Siefert (I964) described a degeneration fluorescein angiography suggested single case with SS disease, and Condon and that the two lesions may have been coincidental. Serjeant (0972b) reported a single case with SC In summary, a distinctive pattern of ocular disease. In two of these reports pseudoxanthoma pathology emerges from the present elderly elasticum was also present, but in the other nine group. Severe grades of peripheral retinal vessel cases the angioid streaks were attributed to sickle- disease are common, and the incidence of retinitis cell disease. In view of these sparse case reports proliferans and of angioid streaks is high, especially the finding of angioid streaks in I3/60 (22 per cent) in those patients over 50 years of age. Some patients patients in the present series is of especial interest are exceptions to this general pattern and have and compares with an incidence of 3/150 (2 per cent) only mild retinal vascular changes despite relatively in younger Jamaican patients (affected cases aged advanced age. These exceptions could be of great 25, 27, and 32 respectively). Angioid streaks interest and may represent variations of homozy- increased in frequency with age in sickle-cell gous sickle-cell disease in which the tendency to disease and they have developed in two patients vessel obstruction is much diminished. aged 25 and 43 in the Jamaican group. Angioid streaks are characterized histologically Summary by defects in Bruch's membrane, and most cases The ocular findings in 6o patients with homozygous have been associated with either pseudoxanthoma sickle-cell disease over the age of 40 years have elasticum or osteitis deformans (Paget's disease). been described. Peripheral retinal vessel disease was The aetiology of angioid streaks in SS disease is common and appeared to increase with age. unknown. Paton (1959) suggested that vascular Retinitis proliferans was common among older obstructions affected the chorio-capillary circula- in the streaks occurred tion, whereas Geeraets and Guerry (I960) thought patients group. Angioid in I3 per cent) patients. http://bjo.bmj.com/ the cause could be an avascular degeneration of (22 elastic tissue consequent on involvement of the We thank the lMlinistry of Overseas Development, posterior ciliary vessels. In this context it is of London, for financial assistance for Mr P. I. Condon interest that three patients with evidence of posterior and to the South-East of Ireland Area Health Board ciliary vessel obstruction developed segmented for granting study leave for Mr Condon to carry out chorioretinal atrophies, but failed to show any the project. on September 30, 2021 by guest. Protected copyright. References CONDON, P. I., and SERJEANT, G. R. (1972a) Amer. _J. Ophthal., 73, 533 , (I972b) Ibid., 74, 921 _ --,---(I972C) Ibid., 74, 1105 -, , and IKEDA, H. ('973) Brit. 7. Ophthal., 57, 8i GEERAETS, w. j., and GUERRY, D. (I960) Amer. J7. Ophthal., 49, 450 GOLDBERG, M. F. (I97I) Ibid., 71, 649 HANNON, J. F. (I956) Ibid., 42, 707 HENRY, M. D., and CHAPMAN, A. Z. (1954) Ibid., 38, 204 HOOK, E. w., and COOPER, G. R. (1958) Sth. med. J. (Bgham, Ala.), 5I, 6io KLINEFELTER, H. F. (1942) Amer. _t. med. Sci., 203, 34 LIEB, W. A., GEERAETS, W. j., and GUERRY, D. (1959) Acta ophthal. (Kbh.), Suppl. 58, I PATON, D. (I959) Arch. Ophthal., 62, 852 SERJEANT, G. R. (I974) 'The Clinical Features of Sickle Cell Disease'. North-Holland, Amsterdam , CONDON, P. I., and SERJEANT, B. E. (1972) 7. Amer. med. Ass., 219, I428 SMITH, E. w., and CONLEY, C. L. (1954) Bull. Johns Hopk. Hosp., 94, 289 SUERIG, K. C., and SIEFERT, F. E. (I964) Arch. intern. Med., 113, I35 WELCH, R. B., and GOLDBERG, M. F. (I966) Arch. Ophthal., 75, 353