Goto, Sugita, Okada, Hatano, Ishiguro, Yoshiki, Ohno

found to be CD2, CD3, CD4, CD25, and HLA-DR positive but CD8 negative. It was revealed,with the particle agglutination method, that theserum titre for HTLV-I was 25 600 timesdilution on repeated tests.

Also, physical examination showed hepato-megaly and hypercalcaemia. Based on thesedata, the diagnosis of ATL was established. Hewas admitted to the department of internalmedicine of Yokohama City University Hospitaland treated with chemotherapy. Initially heappeared to respond well to the therapy, butgradually showed severe complications such asopportunistic respiratory infection and acuterenal failure. Hypoxaemia and hypercalcaemiaprogressively worsened in spite of intensivetherapy. On 22 November 1991, he died in thehospital, and necropsy was carried out. Histo-pathological examination of the eyes revealed theslight infiltration of mononuclear cells in theepisclera, but ATL cells were not found in theeyes (Fig 3). Interestingly enough, on viralexamination the pX region of HTLV-I proviralgenome was detected from the episclera and thesclera with polymerase chain reaction (Fig 4).

CommentAdult T cell leukaemia is a haematologicalmalignancy of high mortality with an increase ofatypical lymphocytes characterised by multipleirregularly lobulated nuclei. Its major ocularmanifestations are opportunistic infectious

lesions and infiltrative lesions by leukaemiccells.2-5 There has been only one report ofepiscleritis associated with ATL,6 but there hasbeen no report ofATL that began with recurrentepiscleritis. It has been reported that HTLV-Iinfects fibroblasts or endothelial cells andtransforms these membrane antigens.7 In thiscase episcleritis recurred many times beforeATL developed, therefore it seems likely thatthis episcleritis may be related to an immuno-mediated reaction to HTLV-I infected cells.Further immunological and molecular biologicalstudies are needed to clarify the exact mechanismof HTLV-I associated ocular diseases. Recog-nition by ophthalmologists of the various ocularinflammatory lesions is important in diagnosingATL.

1 Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H.Adult T-cell leukemia: clinical and hematologic features of16 cases. Blood 1977; 50: 481-92.

2 Ohba N, Matsumoto M, Sameshima M, Kabayama Y, NakaoK, Unoki K, et al. Ocular manifestations in patients infectedwith human T-lymphotropic virus type I. Jpn J Ophthalmol1989; 33: 1-12.

3 Roman GC, Vernant JC, Osame M. HTLV-I and the nervoussystem. Neurology and neurobiology. Vol 51. New York: Alan RLiss, 1989.

4 Kohno T, Arita T, Okamura R. Ocular manifestations inhuman T-lymphotropic virus type I infection. Folia Ophthal-molJpn 1990; 41: 2182-8.

5 Lauer SA, Fischer J, Jones J, Gartner S, Dutcher J, Hoxie JA.Orbital T-cell lymphoma in human T-cell leukemia virustype I infection. Ophthalmology 1988; 95: 110-5.

6 Kabayama Y, Isashiki M, Ohba N, Arima N. Ocular disordersassociated with adult T-cell leukemia. JpnJ Clin Ophthalmol1988; 42: 139-41.

7 Hoxie JA, Matthews DM, Cines DB. Infection of humanendothelial cells by human T-cell leukemia virus type I. ProcNat Acad Sci USA 1984; 81: 7591.

BritishlJournal ofOphthalmology 1993; 77: 744-746

Development of retinal vascular leakage and cystoidmacular oedema secondary to central serouschorioretinopathy

Howard Schatz, Mark D Osterloh, H Richard McDonald, Robert N Johnson

We present what we believe to be the first case ofcentral serous chorioretinopathy to be diagnosed,documented angiographically, and followedand which then developed retinal vascularleakage and cystoid macular oedema. We havedocumented this development with serial fundusphotography and fluorescein angiography.

1 Daniel Burnham Court,Suite 210, San Francisco,CA 94109, USAH SchatzM D OsterlohH R McDonaldR N JohnsonCorrespondence to:Howard Schatz, MD.Accepted for publication31 May 1993

Case reportA 43-year-old man had reduced vision in theright eye for 2 months before being evaluated.On examination, his vision measured 20/30 righteye and 20/15 left eye. The patient had a sensoryretinal detachment of the right macula. Therewas a thin layer of fibrin under the retina justnasal to the fovea, and a small retina pigmentepithelial (RPE) detachment below that (FigIA). There was no sign of intraocular

inflammation, nor any sign of subretinal neo-vascularisation. The left macula showed a fewRPE changes. A fluorescein angiogram con-firmed these findings and showed that there wasan RPE leak into the subretinal space from theshallow RPE detachment in the nasal fovea (FigsIB, IC). A careful stereo examination of theretinal vessels of both fundus photographs andfluorescein angiograms confirmed that the retinalvessels and capillaries were entirely normal andtherewas no cystoid macular oedema. A diagnosisof central serous chorioretinopathy was madeand the patient was followed.The patient returned several months later; the

vision was 20/50 right eye. Examination showedthat cystoid macular oedema had developed inthe right macula. The subretinal fibrin was stillpresent. Fluorescein angiography demonstratedthe presence of leaking retinal vessels and con-

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745Development ofretinal vascular leakage and cystoid macular oedema secondary to central serous chorioretinopathy

Figure IA Right macula, redfree photography. Note theturbid sensory retinal detachment ofthe macula. There is alsoa layer offibrin (pale round area with dark spot in centre)under the retina.

Figure IB Right macula, early phase ofthefluoresceinangiogram. Note the smallRPE detachment inferonasal to themacula. Faint hyperfluorescencejust nasal to the centralfoveawas a shallow RPE detachment inferonasal to the macula.Faint hyperfluorescencejust nasal to the centralfovea was ashallow RPE detachment that had a smallfocal leaking spot.

Figure IC Right macula, later arteriovenous phase ofthefluorescein angiogram. The smallRPE detachmentinferonasal to the macula remains well demarcated andhyperfluorescent. The RPE leakagejust nasal to thefoveashowsfuzzy hyperfluorescence indicatingfluorescein leakageunder the sensory retina.

firmed cystoid macular oedema. Because of theintense leakage into the retinal vasculature, itwas not possible to discerd the presence of an

RPE leak.Three months later, the vision was still 20/50,

but the sensory retinal detachment was slightly

Figure 2A Right macula, redfree photograph. Note the paleappearance ofthe central macula. The tiny dark dots that areseen in this area are small cystic spaces in the retina.

Figure 2B Right macula, early arteriovenous phase ofthefluorescein angiogram. Note the retinal capillaries which arebeginning to leak (giving thefalse appearance ofdilatationand telangiectasis). The smallRPE detachment inferonasal tothefovea appears the same.

Figure 2C Right macula, late phase ofthe cystic macularoedemafrom the leaking retinal capillaries. The RPEdetachment inferonasal to thefovea remains the same.

greater, and the cystoid macular oedemaappeared more pronounced. A repeat angiogramconfirmed the retinal vascular leakage andmarked cystoid macular oedema (Figs 2A-C).The left macula had remained the same.Argon laser photocoagulation was directed to

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Schatz, Osterloh, McDonald, Johnson

the leaking retinal vessels around the right foveain a very light, minimal manner. Over the courseof the next year, the sensory retinal detachmentflattened, the retinal vessels stopped leaking,and the cystoid oedema resorbed. Twelve yearslater, the patient had 20/15 vision in the righteye. There were small RPE laser scars, but thesensory retina was flat and there was no retinalvascular leakage.

CommentWe carefully re-examined all fundus photographsand fluorescein angiograms of this patient. At notime was there any evidence of subretinalneovascularisation. Although the fluoresceinangiogram appeared to show retinal vasculartelangiectatic changes, this was only in appear-ance (false impression), caused by the rapidlyleaking fluorescein through the capillaries.There were no retinal vascular telangiectaticchannels or dilated retinal vessels seen on slit-lamp contact lens examination, stereo fundusphotography, or red free photography. The fine,tiny, dark spots seen in the macula were smallcystic spaces.

Yannuzzi et al' reported that retinaltelangiectases and cystoid macular oedema wereassociated with the sensory retinal detachment ofcentral serous chorioretinopathy. They did notshow, however, that retinal telangiectases (andcystoid macular oedema) developed after centralserous chorioretinopathy had occurred andhad been diagnosed. They noted the retinaltelangiectases only apparent on fluoresceinangiography; no telangiectatic vessels were seenon slit-lamp biomicroscopic examination.

Three mechanisms are possible causes of thebreakdown ofthe inner blood-retinal barrier thatlead to the development of retinal vascularleakage in our case: (1) subretinal fluid damagesthe outer retinal layers causing toxic breakdownproducts in the retina that result in retinalvascular leakage; (2) the subretinal fluid isdirectly toxic to the retinal capillaries; (3) thedetached retina is hypoxic, and this leads toretinal vascular leakage in a compensatory effectto provide more oxygen to the outer retinallayers. The fibrin that appeared attached to thedetached photoreceptors might also have led tohypoxia ofthe retina.

Malbran and colleagues2 reviewed 3260 retinaldetachments and found a 10-7% incidence ofretinal vascular changes in retinas that had beendetached for 6 months or more. This supportsthe idea that prolonged separation of the sensoryretina from the RPE could cause the subsequentdevelopment ofretinal vascular changes, perhapsby prolonged hypoxia and deprivation ofnutrients to the detached retina.

In our patient the-separation ofthe outer retinafrom theRPE may have caused retinal hypoxia ofthe outer retinal layers by separating the outerretina from its normal oxygen supply, thechoroid.34The subretinal fluid may be directly toxic to

the outer retinal layers apart from any hypoxiceffect. The breakdown ofthe photoreceptors andtheir toxic byproducts may alter the retinalcapillaries.The type of subretinal fluid does not appear to

be significant, because fluid of choroidal origin,as in central serous chorioretinopathy,2 orvitreous fluid, as in rhegmatogenous retinaldetachment,5 both appear to be associated withretinal vascular changes. The common factor isdetachment. This tends to support the theorythat direct hypoxia to the outer retinal layerscauses their breakdown, since the two differentsubretinal fluids produce the same effect.

It may be that the subretinal fluid is directlytoxic to the retinal capillaries, and any leakage offluid causes retinal vascular leakage. Experi-mental studies have shown that large moleculeslike horseradish peroxidase can diffuse easilythrough all layers of the retina.5

Supported by the Retina Research Fund of St Mary's Hospital andMedical Center, San Francisco, and by a Grant from the Wayneand Gladys Valley Foundation, San Ramon, California.

1 Yannwzzi LA, Shakin JL, Fisher YL, Altomonte MA.Peripheral retinal detachments and retinal pigment epithelialatrophic tracts secondary to central serous pigment epitheli-opathy. Ophthalmology 1984; 91: 1554-72.

2 Malbran ES, Dodds RA, Huslbus R. Retinal telangiectasiasassociated with longstanding retinal detachment as prog-nostic sign. Mod Probi Ophthalmol 1979; 20: 96.

3 Collier RH. Experimental embolic ischemia of the choroid.Arch Ophthalmol 1967; 77: 683-92.

4 Gay AJ, Goldor H, SmithM. Chorioretinal vascular occlusionswith latex spheres. Invest Ophthalmol VisSci 1964; 3: 647-56.

5 Peyman GA, Bok D. Peroxidase diffusion in the normal andlaser-coagulated primate retina. Invest Ophthalmol Vis Sci1972; 11:35.

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