Bilateral nodular sarcoid choroiditis with vitreous haemorrhage · clinically asfocal sarcoid choroiditis are actually due to granulomas between the retinal pigment epi-thelium and

British Journal of Ophthalmology, 1984, 68, 660-666

Bilateral nodular sarcoid choroiditis withvitreous haemorrhageLAURENCE S. STONE AND MARTIN EHRENBERG

From the Departments ofOphthalmology, Eye Research Laboratories, University of Chicago Medical Center,Chicago, Illinois, and Kansas University Medical Center, Kansas, Kansas, USA

SUMMARY A 21-year-old black man with presumed systemic sarcoidosis had bilateral choroidalnodules, unilateral retinal neovascularisation and vitreous haemorrhage, and non-caseatinggranulomas on percutaneous liver biopsy. The choroidal nodules were serially documented byfundus photography and fluorescein angiography over a 22-month period. Fluorescein angio-graphy was more accurate than ophthalmoscopy in demonstrating choroidal inflammation. Thechoroidal nodules resolved after systemic corticosteroid therapy. A vitreous haemorrhageoccurred probably secondary to neovascularisation related to occlusion of an inferotemporalbranch vein. The non-resolving vitreous haemorrhage and associated traction retinal detachmentwere treated with vitrectomy and membrane sectioning.

Sarcoidosis is an idiopathic, systemic, and non-caseating granulomatous disorder with proteanclinical manifestations. The lymph nodes, lungs,eyes, skin, and viscera are common sites of involve-ment. Ocular involvement has been found to befrom 20 to 50%, depending on the series. 2 Anterioruveitis has always been found to be the commonestocular manifestation of ocular sarcoidosis, occurringin 20 to 90% of patients with systemic sarcoidosis. '1-Involvement of the orbit, eyelids, cornea, lens,lacrimal sac, ciliary body,4 and motor nerves has alsobeen reported.

Posterior segment involvement was consideredrare in a large review series,2 with posterior uveitisfound in only 2-5% of patients. Other workersreported an incidence of posterior uveitis as high as60%.3 It is widely acknowledged that funduschanges are frequently overshadowed by the con-comitant anterior uveitis.5 Posterior segment mani-festations include retinal vascular, chorioretinal,vitreous, and optic nerve inflammatory lesions, aswell as retinal and vitreous haemorrhage.We studied a patient with presumed systemic

sarcoidosis, with bilateral nodular choroiditis, andleft retinal neovascularisation with vitreoushaemorrhage. We carefully documented the course

Corrcspondence to Martin Ehrcnberg, MD, 132 E. 76th Street, NewYork, Ncw York I(X)21, USA.

of the subretinal lesions by serial fundus photo-graphy and fluorescein angiography over a 22-monthperiod; our documentation of these lesions is, to thebest of our knowledge, more detailed than that ofpreviously reported cases. The patient underwentvitreous surgery in the left eye for non-resolvingvitreous haemorrhage and suspected tractionmacular detachment, and he had good recovery ofvision.

Case report

On 24 January 1981 a 21-year-old black man in pre-viously good health came to the University ofChicago Medical Center because of a markeddecrease in left eye vision over the course of twodays. There was no family history of ocular disease.On ocular examination the best corrected visual

acuity was right eye 6/6, left eye hand motions at1 foot (30 cm). Tension by applanation was12 mmHg in each eye, and motility was full. Therewas mild injection of the left bulbar conjunctiva. Anoccasional mutton-fat and an occasional pigmentedpunctate keratic precipitate were present in eacheye. There was a mild degree of flare and cells in theanterior chamber of each eye. The right retrolentalspace was clear; the left retrolental space had a milddegree of cells and flare. Right ophthalmoscopyrevealed about 20 1/4 to 1/2 disc diameter yellowish

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Bilateral nodularsarcoid choroiditis with vitreous haemorrhage

Fig. 1 14 January 1981. Multiple choroidal nodules in theposterior pole ofthe right fundus.

white, slightly elevated, sharply outlined subretinalinfiltrates. They presumably involved the choroidalong the superotemporal, superonasal, and infero-temporal vessels (Fig. 1). There were occasionallylarger, more confluent patches of choroiditis (Fig.2). Fluorescein angiography of these areas showedblockage of the background fluorescence in the earlyarteriovenous phase; in the later venous phase therewas mild staining of the infiltrates (Figs. 3A, B).Temporally, several areas of the flat retiform retinalvessels were present.The left fundus showed a large posterior vitreous

haemorrhage inferotemporally, partially obscuring

Fig. Z 14 January 1951. Conjtuent chorOthe posterior pole ofthe rightfundus.

the disc and macula. The disc was hyperaemic withblurred margins. The superonasal and supero-temporal veins were mildly engorged, dusky, andslightly tortuous, with perivascular superficialhaemorrhages. Temporal to the disc, retinal oedemaand intraretinal haemorrhages were present (Fig. 4).Areas of early neovascularisation arose from veinsthroughout the fundus (Fig. 5). A diaphanousfibrous strand and two large ovoid preretinalhaemorrhages were present superotemporally in theposterior pole (Fig. 6). Several focal, whitish yellow,1/4 to /2 disc diameter lesions, similar in appearance

Fig. 3A Fg. 3B

Fig. 3 14 January 1981. Fluorescein angiogram ofright eye. A: In the early arteriovenous phase, blockage ofthebackgroundfluorescence is present. B: In a later venous phase, there is mild staining of the infiltrates.

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F ig. 4 14 Janulary IY98. Disc hvperaema with blurredmargins, engorgement ofsuperior veins, and retinal oedemaand intraretinal haemorrhage temporal to the disc arepresent in the leftfundus.

to those seen in the fellow eye, were noted along thesuperotemporal arcade.On systemic examination the patient had mild

posterior cervical and inguinal lymphadenopathy.The liver was enlarged to 12 cm and the tip of thespleen was palpable.A percutaneous needle biopsy of the liver re-

vealed non-caseating granulomas surrounded bynon-specific inflammatory cells. The acid-fast

Flg. 6 14 January 19I1. dtwo large ovola preretinalhaemorrhages superotemporally in the leftfundus. Thediaphanous fibrous strand overlying the haemorrhage is notvisible in the photograph.

bacillus stain and cultures for mycobacteria andfungi revealed no organisms. The combined clinical,laboratory, and histopathological findings wereconsistent with systemic sarcoidosis.The patient was started on prednisone, 60 mg

orally every day, on 20 January 1981. Topicaltherapy included atropine 1% drops twice daily andprednisolone acetate 1%O drops four times a day toboth eyes.

Fig. 5 14 January 1981. Areas ofearly neovascularisation Fig. 7 29 January 1981. No choroidal nodules are presentseen nasally in the left fundus. on fundus photography of the posterior pole of the right eye.

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Bilateral nodular sarcoid choroiditis with vitreous haemorrhage

Fig. 8 29 January 1981. Fluorescein angiography cright eye. The late phase ofthe angiogram, showingpersistent staining ofchoroidal nodules.

At ocular examination on 29 January 1981 thepatient's visual acuity was right eye 6/6, left eyecounting fingers at 1 foot (30 cm). Although themajority of the right choroidal infiltrates resolvedclinically (Fig. 7), fluorescein angiography showedstaining in the macular region (Fig. 8), correspond-ing to areas previously visible on ophthalmoscopy.In the left eye the vitreous haemorrhage dispersed,and a yellow-red reflex was visible. As the right eye

improved, the prednisone was gradually reducedover the course of 14 months.The left vitreous haemorrhage failed to clear for

at least eight months. On A and B scan ultra-sonography there was a possible traction maculardetachment (Fig. 9). A left vitrectomy was per-formed on 18 August 1981. The vitreoushaemorrhage was excised and removed. Asuperotemporal preretinal fibrous strand wassevered from its connection with the posteriorvitreous. Postoperatively the visual acuity was lefteye 6/7 5. Superotemporally there was a preretinalstrand which represented an isolated epicentre (Fig.10), and there were macular striae (Fig. 11).On follow-up examination at one year the patient

had no ocular or systemic complaints. Visualacuities were right eye 6/6, left eye 6/6. The rightfundus was normal. In the left eye there was asheathed vein superotemporally, adjacent to theprevious preretinal membrane. In the midvenousphase of the right eye fluorescein angiogram therewere two distinct areas of hyperfluorescencesuperior to the macula. In the late phase of thisangiogram the hyperfluorescence faded, suggestiveof atrophy of the retinal pigment epithelium (Figs.12A, B).

Discussion

There were multiple elevated choroidal nodulespresent in both eyes. Geeraets et al. described four

Fig. 9 On A and B scanultrasonography of the left eye,there is possible traction maculardetachment.

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F-Ig. 1 U 20 August 1 W9J. Preretinal memoranesuperotemporally causing traction on an adjacent venule.

groups of choroidal nodules.6 The first group has afew circumscribed areas of fundus involvement, withflat 1/4 disc diameter round lesions, often locatedclose to retinal vessels. Lesions in the second groupare not always related to blood vessels, appear moreirregular in shape, and are more numerous. Thethird group shows more generalised fundus changes,and larger and more confluent areas of exudativechoroiditis are also present. The fourth group hasadditional factors such as preretinal and intraretinal

r1ig. 11 2( A ugust I oi1. IMaulur striue presentpostoperatively in the left fundus.

haemorrhage associated with different stages ofchorioretinitis. Our case more closely resembles thefourth group.

Initially fluorescein angiography of the nodulesshowed blockage of the background fluorescence inthe early venous phases; in the later venous phasesthere was mild staining of the infiltrates, which onlyfaded slowly. This fluorescein pattern suggestedactive choroidal inflammation. Some choroidalnodules that were seen on fluorescein angiography

Fig. 12A Fig. 12BFig. 12 20 November 1982. A: Midvenous phase offluorescein angiogram ofthe right eye. Two distinct areas ofhyperfluorescence are present superior to the macula. B: In the late phase the hyperfluorescence fades, suggestive ofatrophyof the retinal pigment epithelium.

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Bilateral nodiilar sarcoid choroiditis with vitreous haeemorrhage

were not detected by ophthalmoscopy. Nine daysafter the beginning of systemic steroid therapy therewas almost complete resolution of the choroidalnodules ophthalmoscopically, though fluoresceinangiography continued to show a few areas ofinvolvement.Turner et al.7 described retinal nodules which

leaked fluorescein. Serial documentation of theselesions, however, was not undertaken. Early stain-ing and late leakage from retinal vessel walls inareas of periphlebitis and staining of periphlebiticnodules nave been previously noted." Serial fundusphotography of one area of marked periphlebitiswas performed in one patient with ocular sar-coidosis, but fluorescein angiography was not done.9Fluorescein angiography, performed in two patientswith unilateral macular chorioretinal granulomas,revealed staining of the inflammatory mass withfluorescein leakage of the dye into the neurosensoryspace."' Both patients, who had no retinal neovas-cularisation or vitreous haemorrhage, were treatedwith systemic corticosteroids. One year follow-upfluorescein angiography in both cases revealedcomplete disappearance of the abnormal leakagewith only transmission defects due to the disturb-ance within the pigment epithelium. We have clearlydocumented, by serial fundus photography andfluorescein angiography over a 22-month period,the course of bilateral choroidal nodules in sar-coidosis treated with systemic prednisone.

Histopathologically Laval" has described nodulesof epithelioid cells in the choroid in patients withocular sarcoidosis. However, Gass and Olson' havesuggested that many of the lesions interpretedclinically as focal sarcoid choroiditis are actually dueto granulomas between the retinal pigment epi-thelium and Bruch's membrane.

Active sarcoid choroidal nodules are an indicationfor treatment with systemic corticosteroids, startingwith moderately large doses (60 to 100 mg ofprednisone daily), and tapering according to theclinical responses."' The ophthalmoscopic and angio-graphic changes are the primary means for assessingtherapeutic efficacy. One should exercise caution intapering the systemic corticosteroid dose when thereis angiographic evidence of activity in the absence ofophthalmoscopic signs. In the present case weslowly decreased the systemic corticosteroid dosewith the ophthalmoscopic resolution of the majorityof choroidal nodules while closely monitoring thefluorescein angiogram for total resolution.The second prominent feature of our case was the

left eye vitreous haemorrhage. Several mechanismsof haemorrhage have been described in sarcoidosis.Geeraets et al. observed waxy exudate accumulationon contiguous vessels leading to branch vein

occlusion." Such occlusion can directly result in deepand superficial retinal haemorrhage and vitreoushaemorrhage or predispose to late onset neovas-cularisation, either peripherally or at the optic disc,with subsequent retinal or vitreous haemorrhage.'4Goldberg and Newell'" described a 23-year-old blackman with sarcoidosis who initially had a unilateralsuperotemporal branch vein occlusion which hadbeen replaced by a fibrous band. Six weeks laterthey noted a white mass and new blood vesselsextending three disc diameters into the vitreousfrom the inferonasal margin of the optic disc.A non-specific periphlebitis retinae, similar in its

manifestations to Eales' disease, has been describedin sarcoidosis by many authors7'" and documentedby fluorescein angiography.'7 It seems probable thatvascular involvement in areas of chorioretinalsarcoid inflammation has accounted for some of themanifestations attributed to perivasculitis retinae inthe past.3

Asdourian and coworkers have described angio-graphically seafan neovascularisation and vitreousand retinal haemorrhage in three black patients withsarcoidosis without other systemic disease.' Theypostulated that the periphlebitic process may be thecause of stasis, hypoxia, and a secondary vasopro-liferative stimulus.

In the present case the patient had a large leftposterior vitreous haemorrhage, two large ovoidpreretinal haemorrhages, and a striate haemorrhageoverlying white centres. Engorged, tortuous veins, astrand of fibrous tissue, and multiple areas of flatneovascularisation were present. An inferotemporalvenous occlusion or haemorrhage from retinitis pro-liferans may have accounted for the large preretinaland posterior vitreous haemorrhages. The prognosiswas guarded owing to the possibility of fibrous tissueproliferation associated with traction maculardetachment.

Steroid therapy was not initially directed at thevitreous haemorrhage but rather at the nodularchoroiditis which accompanied it. However, in acase of bilateral sarcoid optic disc neovascularisationwithout haemorrhage, neovascular fronds werefound to respond promptly to oral prednisonetherapy.'" Furthermore, Spalton and Sanders'" hadtwo patients with bilateral optic disc neovascularisa-tion, which disappeared with adequate steroidtherapy and produced no sequelae.

Photocoagulation has not been widely used in thetreatment of neovascularisation secondary to sar-coidosis. In one case of disc neovascularisationargon laser photocoagulation of retinal avascularareas was followed by regression of the disc vessels. '5Asdourian and associates' described one patientwith a seafan type of sarcoid neovascularisation

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treated with focal argon laser photocoagulation.Although the neovascular process was successfullyablated, a neovascular tuft returned in six months.Spalton and Sanders'" have emphasised that ocularinflammation should be well controlled with steroidsbefore any laser treatment is attempted.

In our case a vitrectomy was performed when theleft vitreous haemorrhage did not resolve despite sixmonths of steroid therapy. Important technical con-sideration included the careful removal of the centralvitreous and all preretinal membranes and fibrousstrands. If this had not been done, proliferatingfibrovascular tissue would have led to further retinaltraction and detachment.2"'

This study was supported in part by an unrestricted grant fromResearch to Prevent Blindness, New York, New York.

References

I Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sar-coidosis and its ophthalmic manifestations. Am J Ophthalmol1978; 86: 648-55.

2 James DG, Anderson R, Langley D, Ainslie D. Ocularsarcoidosis. Br J Ophthalmol 1964; 48: 461-70.

3 Crick PR, Hoyle C, Smellie H. The eyes in sarcoidosis. Br JOphthalmol 1961; 45: 461-81.

4 Mizuno K, Watanabe T. Sarcoid granulomatous cyclitis. Am JOphthalmol 1976; 81: 82-5.

5 Asdourian G, Goldberg M, Busse B. Peripheral retinal neovas-cularization in sarcoidosis. Arch Ophthalmol 1975; 93: 787-91.

6 Geeraets WJ, McNeer KW, Maxey EF, Cuerry 111, D.Retinopathy in sarcoidosis. Acta Ophthalmol (Kb/h) 1962; 40:492-5 14.

7 Turner RG, James DG, Friedmann Al, Vijendian M, DaviesPH. Neuro-ophthalmic sarcoidosis. Br J Ophthalmol 1975; 59:657-63.

8 Chumbley LC, Kearns TP. Retinopathy of sarcoidosis. Amn JOphthalmol 1972; 73: 123-31.

9 Dow DS. Ocular sarcoidosis. Am J Ophthalmol 1965; 59: 93-7.1i) Marcus DF, Bovino JA, Burton TC. Sarcoid granuloma of the

choroid. Ophthalmology 1982; 89: 1326-30.11 Laval J. Ocular sarcoidosis. Am J Ophthalmol 1952; 35: 551-4.12 Gass JDM, Olson CL. Saircoidosis with optic ncrve and retinal

involvement. Arch Ophtillinol 1976; 94: 945-50.13 Letocha CE, Shields JA, Goldberg RE. Retinal changes in

sarcoidosis. Can J Ophthalmnol 1975; 10: 184-91.14 Sanders MD, Shilling JS. Retinal, choroidal, and optic disc

involvement in sarcoidosis. Trans Ophthalmol Soc UK 1976;96: 140-4.

15 Goldberg S, Newell FW. Sarcoidosis with retinal involvement.Arch Ophihalmol 1944; 32: 93-6.

16 Cross AG. Ocular sarcoidosis. Trants Ophthalmol Soc UK 1955;75: 181-7.

17 Algvere P. Fluorescein studies of retinal vasculitis in sar-coidosis. Acta Ophthalmnol (Kbh) 1970); 48: 1129-39.

18 Doxanas MT, Keliley JS, Prout TE. Sarcoidosis with neovas-cularization of the optic nerve head. Amn J Ophihalmol 198(0; 90:347-51.

19 Spalton DJ, Sanders MD. Fundus changes in histologicallyconfirmed sarcoidosis. Br J Ophthalmnol 1981; 65: 348-58.

2(0 Treister G, Machemer R. Results of vitrectomy for rareproliferative and hemorrhagic diseases. Amn J Ophthalmol 1977;84: 394-412.

21 Machemer R. Pathogenesis of proliferative neovascular retino-pathies and the role of vitrectomy. A hypothesis. IntOphthalmol 1978; 1: 1-3.

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Bilateral nodular sarcoid choroiditis with vitreous haemorrhage · clinically asfocal sarcoid choroiditis are actually due to granulomas between the retinal pigment epi-thelium and