BritishJournal ofOphthalmology 1993; 77: 349-353 3349

Subretinal exudative deposits in central serous

chorioretinopathy Br J Ophthalmol: first published as 10.1136/bjo.77.6.349 on 1 June 1993. Downloaded from

Darmakusuma Ie, Lawrence A Yannuzzi, Richard F Spaide, Maurice F Rabb, Norman P Blair, Mark J Daily

Abstract ments,' are generally not associated with sub- The presence of subretinal exudation in a retinal exudative deposits. patient with neurosensory detachment of the We evaluated a group of 11 patients with macula frequently suggests the diagnosis of central serous chorioretinopathy who had sub- choroidal neovascularisation. A retrospective retinal exudative deposits for the following chart review of newly diagnosed cases of purposes: firstly, to identify non-pregnant central serous chorioretinopathy revealed 11 women as another subgroup of central serous patients, seven men and four non-pregnant chorioretinopathy patients who develop sub- women, who had plaques of subretinal retinal exudative deposits; secondly, to describe exudate, which presumably were fibrin. the findings and clinical course of these patients Department of , Each of these patients had a solitary plaque more completely than in previous papers; Manhattan Eye, Ear and that ranged in size from 300 to 1500 tim in thirdly, to define characteristics of subretinal Throat Hospital, New diameter. These patients had no signs or a exudative deposits that differentiate them from York DIe clinical course suggestive of choroidal neo- the typical exudate seen in choroidal neovascu- L A Yannuzzi vascularisation. In each case the subretinal larisation; fourthly, to hypothesise a mechanism R F Spaide plaque was overlying an exuberant leak in the integrating results from previous studies by pigment was Department of retinal epithelium. The exudate which subretinal exudative deposits form. Ophthalmology and generally present at the initial examination, Patients were selected retrospectively from the Visual Sciences, UIC Eye and usually showed dissolution before or files of the contributing authors. Central serous Center, University of coincident with the resolution of the neuro- chorioretinopathy was defined as an idiopathic Illinois at Chicago College ofMedicine and sensory detachment. After resolution of the detachment of the neurosensory , associ- Mercy Hospital and central serous chorioretinopathy, patients ated with focal or multifocal leaks at the level of Medical Center, Chicago, were left with subtle alterations in the retinal the retinal epithelium demonstrable on Illinois pigment M F Rabb pigment epithelium in the areas of the sub- fluorescein angiography. The patients had com- retinal plaque. These findings are important plete ophthalmic examinations, fundus colour Laboratory ofRetinal for two reasons. Firstly, the presence of sub- photography, and fluorescein angiography. All Circulation and Metabolism, Department retinal exudation does not necessarily rule out patients were followed at least until the resolu- ofOphthalmology and the diagnosis of central serous chorioretino- tion oftheir primary detachments. http://bjo.bmj.com/ Visual Sciences, UIC Eye pathy. Secondly, pathophysiological theories Center, University of serous must Illinois at Chicago of central chorioretinopathy College of Medicine, explain how the plaques are deposited behind Results Chicago, Illinois the retina. The 11 patients included seven men and four N P Blair (BrJ Ophthalmol 1993; 77: 349-353) women (Table 1). All were newly diagnosed and Department of all were in good health and none of the women Ophthalmology, Loyola were pregnant. The mean age ofthe patients was on September 28, 2021 by guest. Protected copyright. University Medical Neurosensory detachment of the macula can 41 (SD 6) years with a range from 29 to 48 years. School, Maywood, Illinois occur in adults for a variety of reasons; some The mean age of the four women was 40 years, M J Daily conditions require prompt treatment while considerably older than the mean of age of 31 Correspondence to: others can be expected to resolve spontaneously. reported by Gass in his series of pregnant Dr L A Yannuzzi, were Manhattan Eye, Ear and The presence of subretinal exudative deposits patients.' Six were Caucasian, three Asian, Throat Hospital, 210 East 64th may suggest the presence of choroidal neo- and two were Hispanic. Refractive errors were Street, New York, NY 10021, USA. vascularisation. On the other hand, central plano to + 1 00 in all patients following resolu- Accepted for publication serous chorioretinopathy, except in pregnant tion of the macular detachment except for one 26 January 1993 women' or cases ofatypical large bullous detach- patient who was -2-25. None ofthe patients had angioid streaks, peripheral punched out chorio- Table I Patient characteristics retinal atrophic spots, peripapillary atrophy, , or soft drusen. Agelsexl Initial visual Final visual Presence of Laser In each case there was a neurosensory detach- Patient race* acuity acuity RPEDt treatment ment associated with a solitary, focal, feather- 1 44/WA 20/400 20/70 Yes No edged plaque on the undersurface of the retina 2 35/F/W 20/25 20/25 Yes No 3 43/M/W 20/70 20/200 Yes No (Fig 1). The placoid deposits were generally 4 38/M/W 20/100 20/20 Yes No greyish-white to white, but were occasionally 5 48/F/W 20/25 20/25 Yes No 6 47/M/W 20/60 20/100 Yes Yes cream-coloured. These deposits were trans- 7 29/F/W 20/70 20/20 Yes No lucent to retroillumination. No patient had 8 44/M/H 20/200 20/25 No Yes 9 37/WA 20/200 20/40 Yes Yes haemorrhage or cystoid macular oedema, which 10 40/WA 20/80 20/20 Yes Yes can be signs suggestive of choroidal neovascu- 11 48/F/H 20/200 20/30 Yes Yes larisation. No patient had the bright, yellow *A=Asian; W=Caucasian; H=Hispanic. white deposits under the retina characteristic of tRPED=retinal pigment epithelial detachment. lipid. Confusion initially caused by the greyish- 350 Ie, Yannuzzi, Spaide, Rabb, Blair, Daily

Figure 1(A) A 48-year-old woman with a history of reduced vision in the right eye ofseveral days' duration. There is a neurosensory Br J Ophthalmol: first published as 10.1136/bjo.77.6.349 on 1 June 1993. Downloaded from in the temporal macula overlying a yellowish deposit ofexudate. In the inferonasal macula, there is another serous detachment ofthe retinal pigment epithelium.

Figure (B) The early venousphasefluorescein angiogram reveals hyperfluorescencefrompooling beneath the serous detachments ofthe retinalpigment epithelium. The superior white appearance of the plaques led to mistaken pigmentepithelialdetachment is associatedwith afocal leak at diagnoses of choroidal neovascularisation, its temporal margin. , and, in one patient, an infiltrative metastatic process to the . The subretinal exudative deposit was found between the arcades decline to 20/100. The other two patients, one in 10 of the 11 patients; in one patient it was followed for 8 and one for 9 years, demonstrated found nasal to the disc. no recurrences and visual acuity recovery to The exudate varied in size from 300 pm to 20/20. Nopatientintheseriesdevelopedchoroidal 1500 ,um in diameter. The size ofthe exudate did neovascularisation. not seem to correlate with size of the detach- The dissolution of the exudate did not neces- ment. In our cases, the subretinal exudative sarily parallel the course of the macular detach- deposit often had a partial or complete ring ment. It was usually present at the time of appearance where the centre was thinner and diagnosis. In some cases, the exudate dis- more pellucid than the edges. The inferior appeared long before the sensory retinal detach- portion of the exudate was usually thicker than ment resolved. In a few patients, the ring of the superior portion. exudate persisted surrounding a serous pigment On fluorescein angiography the subretinal epithelial detachment for a variable period after exudative deposit was consistently found the resolution ofthe sensory retinal detachment. directly above or adjacent to a robust leak from In others, the disappearance of the exudate the level of the retinal pigment epithelium (Fig coincided with the resolution of the sensory 2). The exudate did not block the underlying retinal detachment. Some patients were left with detach- a subtle discoloration in the area of the fluorescence. A retinal pigment epithelial greyish http://bjo.bmj.com/ ment was found in 10 of the 11 patients, and the subretinal exudative deposit. leak was almost always at or very near the edge of the retinal pigment epithelial detachment. In a few patients the ring of subretinal exudation Discussion encircled the retinal pigment epithelial detach- The subretinal deposition described in this ment like a halo. No patient had evidence of report appears to be a primary manifestation of

retinal vascular leakage. central serous chorioretinopathy. Recognised on September 28, 2021 by guest. Protected copyright. A majority of our cases had spontaneous secondary alterations in central serous chorio- resolution of their detachments in 3-6 months. Five patients were treated by laser photocoagula- tion (Fig 3). One author (LAY) followed three patients for more than 7 years. One of these patients experienced chronic and recurrent acute detachments with progressive perifoveal atrophy, cystic , and visual

Figure 1(D) A photograph ofthe same patientfollowing 'Figure I1(C) A late venous laserphotocoagulation treatment to the pigment epithelial leak phasefluorescein angiogram in the superior macula. There has been resolution ofthe reveals an increase in the neurosensory retinal detachment andflattening ofthe serous pigment epithelial leak at the detachment ofthe retinal pigment epithelium in the superior temporal aspect ofthe macula. The inferiorpigment epithelial detachment persists. pigment epithelial The exudate which was surrounding the pigment epithelial detachment in the superior detachment in the macula has also resolved, and the maculaforming an 'ink photocoagulation has left a slight atrophic defect at the blot'. treatment site. Subretinal exudative deposits in central serous chorioretinopathy 351

Figure 2(A) Colour photograph ofa 44-year-old man with a history ofchange in vision ofseveral days'

duration. There is an Br J Ophthalmol: first published as 10.1136/bjo.77.6.349 on 1 June 1993. Downloaded from exudative detachment ofthe neurosensory retina with an irregular area ofsubretinal yellowish exudate near the fovea.

Figure 2(B) The late stagefluorescein angiogram reveals the presence ofa serous detachment ofthe retinalpigment include capillary telangiectasis,3 epithelium with overlying retinalpigment epithelial retinal capillary non-perfusion,3 retinal neovas- hyperplasticfigures in the central macula. There is a 'smokestack' leak emanatingfrom apoint nearorat the margin cularisation,4 lipid deposition, cystoid macular ofthe retinalpigment epithelium, ascending in the oedema, dependent retinal detachment,25 retinal subneurosensory retinalspace anddecussating temporally more pigment epithelial descending tracts,3 and than nasally. Some ofthe subretinalfluid has been stained choroidal neovascularisation. Most, if not-all, of withfluorescein, more clearly delineating thefull extent ofthe these changes represent sequela associated with neurosensory detachment. chronic disease. They have not been associated with primary detachment ofthe macula in newly egress offluid and protein under the retina. This diagnosed cases such as the patients described in phenomenon has recently been described in this series. cases ofage-related macular degeneration.8 Some of the patients in this report were The subretinal exudative deposition associ- initially suspected ofhaving choroidal neovascu- ated with central serous chorioretinopathy larisation because of the exudate. However, differed in character and location from that seen biomicroscopic examination ofthese patients did in choroidal neovascularisation. In acute stages not reveal turbid subretinal fluid or haemor- of choroidal neovascularisation, the two most rhage. In addition, these patients did not have common materials deposited under the retina are angioid streaks, chorioretinitis, or chorioretinal blood and lipid. Blood is most commonly seen atrophic spots, which in young people are some- near the area of choroidal neovascularisation or times associated with choroidal neovascularisa- along the dependent edge of the neurosensory tion. Furthermore, the clinical course, with detachment. Lipid is most commonly seen at the improvement in signs and symptoms even with- rim of the neurosensory detachment and is out laser treatment, also was consistent with the characterised by yellow white, hard-edged, diagnosis ofcentral serous chorioretinopathy. opaque subretinal flecks. The deposits seen in http://bjo.bmj.com/ On fluorescein angiography, almost all of the present series ofpatients were feather edged, these patients had a retinal pigment epithelial greyish-white, translucent, and occurred in close detachment with a focal leak from its edge. The proximity to the fluorescein leak. subretinal exudative deposit typically was a focal The composition of the subretinal exudative deposit that appeared to overlie the leak. 'Blow deposits is not well established. The material did outs' of the retinal pigment epithelium have not appear to be lipid. The patients in this and a previously been described,6 but these 'blow outs' previous report' did not appear to have systemic on September 28, 2021 by guest. Protected copyright. occurred on the surface of the retinal pigment inflammatory disease or clinical evidence of epithelial detachment. It has been shown that the ocular inflammation, making the possibility of area of maximal stress is at the margin of a subretinal white cell deposition unlikely. Histo- pigment epithelial detachment.7 It is possible pathological and histochemical studies of one that the patients described in this report have a case of central serous chorioretinopathy has 'subclinical blow out' of the retinal pigment shown the presence of subretinal and subpig- epithelium at the border of the retinal pigment ment epithelial fibrin.9 Histopathological analy- epithelial detachment, allowing the abnormal sis has revealed the presence of a high protein content within the subretinal fluid.'0 This high concentration of protein may be the cause of smokestack leaks seen in central serous chorio- retinopathy."I These studies, as well as the clinical appearance of the deposits, suggest that there is proteinaceous material, including the possibility of fibrin, present in the subretinal Figure 2(C) A colour space in central serous chorioretinopathy which photograph ofthe same to the formation ofa subretinal patient I week later reveals might contribute complete, spontaneous exudative deposit. resolution ofthe neurosensory Previous hypotheses regarding the pathogene- detachment and subretinal sis of central serous chorioretinopathy have exudate. The serous detachment ofthe retinal proposed a derangement of retinal pigment pigment epithelium is still epithelial function as the initiating cause in present in the central macula. central serous chorioretinopathy. 12-14 The nature 352 Ie, Yannuzzi, Spaide, Rabb, Blair, Daily Br J Ophthalmol: first published as 10.1136/bjo.77.6.349 on 1 June 1993. Downloaded from

Figure 3(A) A colourphotograph ofa 40-year-old man with a I week history ofreduced vision in the left eye. There is a Figure 3(B) The early venousphasefluorescein angiogram neurosensory retinal detachment overlying a deposit ofexudate reveals some window defect in the nasal macula and afocal which partially obscures a serous detachment ofthe retinal leak at or near the edge ofa serous detachment ofthe retinal pigment epithelium which isjust superotemporal to thefoveal pigment epithelium. region. This pigment epithelial detachment was clinically obscured by the exudate.

Figure 3(D) The same patientfollowing laser Figure 3(C) Late venous phasefluorescein angiogram photocoagulation treatment. Note the resolution ofthe reveals a progressive increase in thepigment epithelial leak neurosensory detachment and subretinal exudate. with pooling ofthe subneurosensory retinal space. A small, irregular serous detachment ofthe retinalpigmentepithelium in http://bjo.bmj.com/ the nasal macula is also evident.

of the retinal pigment epithelial dysfunction subretinal deposition of material, which was remains unclear. Negi and Marmor" believe a believed to be proteinaceous and possibly metabolic disturbance and failure of the retinal fibrinous in nature. In contrast to previous

pigment epithelial cell ion pumping mechanism reports, four non-pregnant women were noted in on September 28, 2021 by guest. Protected copyright. is responsible, whereas Spitznas'3 argues that our series to have subretinal exudative deposits. central serous chorioretinopathy occurs second- The subretinal deposits were feather-edged, ary to a reversal in the direction ofion pumping. greyish white, translucent plaques overlying If the composition of the subretinal exudative or closely associated with a leak at the level of deposit is fibrin, a considerable alteration in the the retinal pigment epithelium, which is not normal physiology of the choriocapillaris, characteristic in appearance or location for a Bruch's membrane, and the retinal pigment subretinal deposit associated with choroidal neo- epithelium must occur. For fibrin to form on the vascularisation. The accompanying clinical and undersurface ofthe retina, fibrinogen, the mono- fluorescein angiographic findings, as well as the meric precursor offibrin, must gain access to the clinical course ofthese eyes, were consistent with subretinal space. Fibrinogen has a molecular the diagnosis of central serous chorioretino- weight of 343 000 daltons,5 which is about five pathy. For protein, or more specifically fibrin, to times greater than albumin, a protein shown to be present in the subretinal space and on the be restricted by the choriocapillaris. 6 outer surface of the retina, a breakdown in the After resolution of the subretinal fluid and normal physiology of the choriocapillaris, dissolution of the exudative deposit some Bruch's membrane, and the retinal pigment patients had a permanent alteration in the epithelium must occur. appearance of the underlying retinal pigment This work was supported in part by the LuEsther T Mertz Retinal epithelium. This altered appearance may be Research Laboratory and the Macula Foundation, Manhattan Eye, Ear and Throat Hospital, 210 East 64th Street, New York, from residua ofthe subretinal exudative deposit, USA. from healing of the underlying retinal pigment NY 10021, 1 Gass JDM. Central serous chorioretinopathy and white sub- epithelial detachment, or from fibrous meta- retinal exudation during pregnancy. Arch Ophthalmol 1991; plasia ofthe retinal pigment epithelium. 12 109: 677-81. 2 Gass JDM. Bullous retinal detachment: an unusual manifesta- The 11 patients described in this report had tion of idiopathic central serous choroidopathy. Am J central serous chorioretinopathy associated with Ophthalmol 1973; 75: 810-21. Subretinal exudative deposits in central serous chorioretinopathy 353

3 Akiyama K, Kawamura M, Ogata T, Tanaka E. Retinal presentation at VerhoeffSociety Meeting, Washington, DC, vascular loss in idiopathic central serous chorioretinopathy 24-25 April, 1982. with bullous retinal detachment. Ophthalmology 1987; 94: 10 Ikui H. Histologic examination of central serous retinopathy. 1605-9. Nippon Ganka Kiyo 1969; 20: 1035-41. 4 Yannuzzi LA, Shakin JL, Fisher YI, Altomonte MA. 11 Shimizu K, Tobari I. Central serous retinopathy dynamics of Peripheral retinal detachments and retinal pigment subretinal fluid. Mod Prob Ophthalmol 1971; 9: 152. Br J Ophthalmol: first published as 10.1136/bjo.77.6.349 on 1 June 1993. Downloaded from epithelial atrophic tracts secondary to central serous 12 Negi A, Marmor M. Experimental serous retinal detachment pigment epitheliopathy. Ophthalmology 1984; 91: 1554- and focal pigment epithelial damage. Arch Ophthalmol 1984; 72. 102:445-9. 5 Urayama A, Hatakeyama T, Machida A, Abe N. Two cases of 13 Spitznas M. Pathogenesis of central serous retinopathy: a new central chorioretinitis followed by retinal detachment. JapJ working hypothesis. Graefes Arch Clin Exp Ophthalmol Clin Ophthalmol 1971; 25: 731-5. 1986; 224: 321-4. 6 Goldstein BG, Pavan PR. 'Blow outs' in the retinal pigment 14 Piccolino FC. Central serous chorioretinopathy: some con- epithelium. BrJ Ophthalmol 1987; 71: 676-81. siderations on the pathogenesis. Ophthalmologica 1981; 182: 7 Krishan NR, Chandra SR, Stevens RS. Diagnosis and patho- 204-10. genesis of retinal pigment epithelial tears. AmJ7 Ophthalmol 15 Williams WJ, Beutler E, Ersleu A, Lichtman M. Hematology. 1985; 100: 698-707. New York: McGraw-Hill, 1983: 1222-38. 8 le D, Yannuzzi LA, Spaide RF, Woodward KP, Singerman 16 Pino RM. Restriction to endogenous plasma proteins by a LJ, Blumenkranz MS. Microrips of the retinal pigment fenestrated capillary endothelium: an ultrastructural epithelium. Arch Ophthalmol 1992; 110: 1443-9. immunocytochemical study of the choriocapillary endo- 9 de Venecia G. Fluorescein angiographic smoke stack: case thelium. Am3'Anatomy 1985; 172: 27989. http://bjo.bmj.com/ on September 28, 2021 by guest. Protected copyright.