The Uveal Effusion Syndrome and Trans-Scleral Flow

Eye (1990) 4, 354-365

J. V. FORRESTER,* W. R. LEE, P. R. KERR, H. S. DUA* Aberdeen and Glasgow

Summary Recent studies of the uveal effusion syndrome, a rare condition characterised by idiopathic spontaneous serous detachment of the retina and peripheral choroid, have suggested a primary scleral abnormality as the underlying cause. In particular, abnormal deposition of glycosaminoglycans within the sclera· may impair normal trans-scleral flow of fluid and contribute to increased scleral thickness. In four cases of uveal effusion syndrome, we have confirmed the accumulation of glycosaminogly cans in the sclera. Histochemical studies show that most of this material is pro teodermatan sulphate with a smaUer contribution from proteochondroitin sulphate, while electron microscopy showed an increase in collagen fibril thickness. Secondary changes within the retinal pigment epithelium were also observed, particularly foci of proliferation which corresponded to the characteristic 'leopard-spot' fundal appearances of this disorder. We therefore suggest that the uveal effusion syndrome is due to a primary defect in proteodermatan synthesis and/or degradation by scleral fibroblasts and may represent a form of ocular mucopolysaccharidosis.

Spontaneous serous detachment of the chor and probably also pathogenetically, distinct oid was described clinically by von Graefe in from serous detachments in nanophthalmic 18581 and histologically by Verhoeff and eyes, where the eye is small and there is Waite.2 This rare condition is characterised by chronic hypotony.5 The pathogenesis of idio serous detachment of the peripheral choroid pathic serous detachment is obscure. On clini and ciliary body in an annular fashion with cal evidence of marked episcleral venous bullous, shifting non-rhegmatogenous retinal distension, it has been suggested6 that fluid detachment. Both eyes are usually affected, accumulation may be due to impairment of sometimes with a time interval in onset, and in venous drainage secondary to the extensive some series males predominate.3 Patients may scleral thickening previously observed.3 Gass present when vision deteriorates due to and Jallow4 observed that Schlemm's canal involvement of the macula in the exudative frequently filled with blood indicating ele detachment.4 Gass and Jallow4 described sev vated back venous episcleral pressure, and eral other characteristic features including the fluorescein angiography has confirmed that leopard-spot pigment epithelial changes, the choroidal perfusion (flow) is significantly consistent ultrasonic evidence of choroidal delayed.6 Several other conditions which may thickening and of peripheral choroidal and be associated with impaired venous drainage, ciliary body detachment. are characterised by choroidal detachments Idiopathic serous detachment of the chor including compressive and/or inflammatory oid and retina is usually considered clinically, diseases of the orbit and globe (e.g. scleritis,

From: Department of Ophthalmology, University of Aberdeen' and Department of Pathology, University of Glasgow.

Correspondence to: Professor J. V. Forrester, Department of Ophthalmology, Aberdeen University Medical School, Foresterhill, Aberdeen AB9 2ZD. THE UVEAL EFFUSION SYNDROME AND TRANS-SCLERAL FLOW 355

Table I Uveal effusion syndrome: clinical data

Age Sex Presentation Laterality Outcome

Case 1 65 F Visual loss, progressive inferior RD? solid Unilateral Enucleation Case 2 64 M Visual loss, rapid inferior RD? solid Unilateral Enucleation Case 3 56 M Visual loss, gradual total RD? annular melanoma Unilateral Enucleation Case 4 63 M Visual loss, gradual inferior RD pigmentation Bilateral Scleral resection

scleral buckling procedures), vortex vein characterised by the thickened sclera. A anomalies and pan-retinal photocoagulation similar observation was noted in a rare case of

(for review see ref 7) _ On this basis, therefore, uveal effusion syndrome associated with treatment of spontaneous uveal effusion by Hunter's syndrome,l1 in which there are decompression of the vortex veins has been abnormal deposits of glycosaminoglycans in attempted8'9 with varying success. the tissues, including the sclera. More GasslO also found that' simple lamellar recently, increased quantities of scleral glyco resection of the sclera produced as good a saminoglycans were demonstrated by light result as the more difficult operation of vortex and electron microscopy in a case of idio vein decompression. He hypothesised that pathic uveal effusion symdrome.12 protein-rich choroidal and sub-retinal fluid If Gass is correct, and there is compelling accumulated because of a scleral abnormality, circumstantial evidence to support him, then

Fig. lao Fig. lb. Fig. 1. Sections of whole eyes stained with periodic acid Schiff reagent. (a) control eye (exenteration specimen); (b) uveal effusion eye (case 3). Note gross oedema of uvea in (b) with increased scleral thickness and intensity of stain in sclera. Control specimen shows artificial detachment of retina (Mag xl.S). 356 J. V. FORRESTER ET AL.

Table II Uveal effusion syndrome, Alcian blue inal pigment epithelial cell layers, which may staining have been secondary to the long standing ret Scleral stain intensity' inal detachment, but which correlate clini cally with the 'leopard-spot' fundal changes. Anterior Posterior pHO.4pH1.0pH2.5 pH0. 4pH 1. 0pH2.5 Materials and Methods

Control A 0.5 0.5 0.5 1.0 0.5 2.0 Cases Control B 0.5 1.0 0.5 0.5 0.5 0.5 Ocular tissue from four cases of idiopathic

Case 1 2.0 2.0 4.0 2.0 1.0 4.0 uveal effusion syndrome have been received Case 2 2.0 2.5 3.0 2.0 3.0 3.0 by the Department of Pathology, University Case 3 2.0 2.5 3.0 3.0 3.0 3.0 of Glasgow during the period 1977-1987 Case 3 2.5 3.0 2.5 (Table I). In three cases, the entire globe was enucleated due to clinical suspicion of ocular • 0 = nil; 1 = minmal; 2 = mild; 3 = moderate; 4 = marked. melanoma. In the fJurth case, strips of sclera were obtained after a scleral resection it would be important to identify the glycosa procedure. minoglycans or more accurately the prote Case 1: A 65-year-old female with a history of sev oglycans, which are present in excess in the eral weeks progressive loss of upper nasal visual sclera in the uveal effusion syndrome. Normal field loss, was found to have a lower temporal, clini sclera contains low to moderate amounts of cally 'solid' retinal detachment. The fellow eye was proteoglycans (PGs) as either low molecular normal. The eye was enucleated on suspicion of a weight, 'small' proteoglycans, or high mol choroidal melanoma. ecular weight 'large' proteoglycans each form Case 2: A 64-year-old male with a history of rapid containing variable amounts of chondroitin loss of vision in the left eye over a lO-day period, sulphate and dermatan sulphate. Proteogly was found to have an extensive retinal detachment particularly on the temporal aspect of the globe. cans confer tissue resistance to the bulk flow Ultrasound examination suggested that this was a of fluid and the diffusion of water through a solid detachment, and clinically no retinal holes PG filled matrix. This presumably varies with were observed. The eye was enucleated on sus the hydrodynamic volume of the constituent picion of ocular tumour. glycosaminoglycans which is reflected in the Case 3: A 56-year-old male presented with a four swelling pressure of the tissue. If the scleral month history of gradual deterioration of vision in PGs in the uveal effusion syndrome represent the right eye. Examination revealed a total retinal an excessive production or decreased rate of detachment without retinal holes. The ciliary body degradation of normally present PGs, then appeared thickened inferiorly for 1800 and was the accumulation of protein-rich fluid within associated with a 'tense' detached retina. Transil lumination of the globe was uninformative. The fel the choroid and subscleral space, probably low eye was normal. A clinical diagnosis of annular represents increased resistance to the bulk melanoma of the ciliary body was made and the eye transfer of protein across the sclera. was enucleated. We have had the opportunity to study histo Case 4: A 63-year-old male presented with gradual pathologically four cases of idiopathic uveal but variable deterioration of vision of the right eye effusion syndrome. In three cases the eyes for two to three months. Examination revealed a had been removed on clinical suspicion of shallow inferior retinal detachment extending up to malignant melanoma, while in the fourth case the macula. A characteristic 'leopard spot' pigmen the diagnosis was reached prior to surgery and tation was observed in the fundus together with only resected scleral tissue was available for extensive 3600 thickening of pars plana ciliaris. The left eye also showed a thickened ciliary body for examination. Enzyme histochemistry con 2700 mainly inferiorly but there was no retinal firmed that the excess glycosaminoglycan was detachment. A diagnosis of idiopathic uveal effu predominantly derma tan sulphate with some sion syndrome was made. increase in chondroitin sulphate. Electron A course of systemic steroids had no effecton the microscopy also confirmed the abnormal subretinal exudate and scleral resection in four scleral collagen changes. In addition, quadrants were performed, as described by Gass9 abnormalities were also observed in the ret- but without sclerotomy or sclerostomy. Consider- THE UVEAL EFFUSION SYNDROME AND TRANS-SCLERAL FLOW 357

1 2 2 I

3 4 3 4 !

5 6 5 6

Fig.2a. Fig.2b. Fig. 2. Alcian blue stain of ocular coats. (a) anterior sclera, uvea and ora serrata/pars plana; (b) posterior (macular) region. (1)(3)(5), control tissue; (2)(4)(6), uveal effusion tissue. (1)(2), pH 0. 4; (3)(4), pH 1. 0; (5)(6), pH 2. 5 (Mag x 40).

able transudation of fluid from the site of scleral exenteration procedures for extensive orbital tum resection was observed at surgery. During the ensu ours. The globes were immersion fixed in phos ing weeks, vision improved from 6/60 to 6/9 with phate buffered glutaraldehyde and processed for resolution of the detachment and visual improve histochemical analysis as outlined below. ment has been maintained for 18 months. Control Tissue: Two specimens of freshly enu Tissue preparation cleated globes were obtained during the course of Enucleated globes from cases 1 to 3 were

Table lila Uveal effusion syndrome. Alcian blue Table IIIb Uveal effusion syndrome, Alcian blue staining after Enzyme Digestion of Sclera staining after Enzyme Digestion of Sclera Anterior scleral stain intensity (Alcian blue pH 2. 5)* Posterior scleral stain intensity (A lcian blue pH 2. 5)*

Control Control Case Case Control Control Case Case Enzyme A B I 3 Enzyme A B I 3

None 0.5 0.5 4.0 3.0 None 2.0 0.5 4.0 3.0 Testicular Testicular Hyaluronidase 0 0.0 2.0 1.5 Hyaluronidase 0.5 0.0 2.0 2.0 Streptomyces Streptomyces Hyaluronidase 0.5 1.0 3.5 2.5 Hyaluronidase 3.0 1.0 4.0 3.0 Chondroitinase ABC 0.0 0.0 1.5 1.0 Chondroitinase ABC 1.0 0.0 2.0 1.5 Chondroitinase AC 0.5 0.5 3.5 3.0 Chondroitinase AC 1.0 0.5 4.0 3.0 Neuraminidase 1.0 0.5 4.0 4.0 Neuraminidase 3.0 0.5 4.0 4.0

• 0 = nil; 1 = minimal; 2 = mild; 3 = moderate; 4 = * 0 = nil ; 1 = minimal; 2 = mild; 3 = moderate; 4 = marked. marked. �- - -

1 2 3

i�

.. - -

4 5 6

Fig.3a.

1 2 3

4 5 6

Fig.3b.

Fig. 3. Enzyme histochemistry of normal eye post-stained with Alcian blue, pH 2. 5. (a) anterior segment; (b) posterior segment. Sections were pretreated with (1) no enzyme (2) testicular hyaluronidase (3) streptomyces hyaluronidase (4) chondroitinase ABC (5) chondroitinase AC (6) neuraminidase. Note difference in staining intensity between anterior sclera (a, 1) and posterior sclera (b, 1). Note preferential reduction in stain with testicular hyaluronidase (a,2; b,2) and chondroitinase ABC (a,4; b,4) (Mag x40). 1 2 3

Fig.4a.

-----� . ------" 1------�--� 1 2 3

-- . -. -" - .-- -- - . _._ .....-- � ------...... -- �- i-""" 4 5 6

Fig.4b.

Fig. 4. Enzyme histochemistry of uveal effusion eye post-stained with Aldan blue, pH 2.5. (a) anterior segment, (b) posterior segment. Sections were pretreated with (1) no enzyme (2) testicular hyaluronidase (3) streptomyces hyaluronidase (4) chondroitinase ABC (5) chondroitinase AC (6) neuraminidase. Note reduction in stain with testicular hyaluronidase (a,2; b,2) and chondroitinase AB C (a,4; b,4) (Mag X40). 360 J. V. FORRESTER ET AL.

Fig. 5. Electron microscopy of scleral tissue from control (a,c) and uveal effusioneyes (b, d) . Note deposition of interfibrillar electron-dense material (b) and relative increase in fibril thickness (d) compared to control tissue. Bar = llWl.

immersed in cacodylate-buffered gluteralde scleral tissue from Case 4 (4 x 4 mm blocks) hyde and processed by conventional means was similarly prepared for light and electron for light and electron microscopy. Resected microscopy. THE UVEAL EFFUSION SYNDROME AND TRANS-SCLERAL FLOW 361

Fig. 6. Histological section of PAS stained uveal effusion tissue. Note dilated engorged choroidal veins, PAS positive inclusion in RPE layer and migration and proliferation of RPE cells in the suhretinal space (Mag x250).

Histochemical stains at 37°C (digests hyaluronic acid, chondroitin In addition to haematoxylin and eosin stain -4 and -6 sulphate and dermatan sulphate); ing for light microscopy, the following special streptomyces hyaluronidase, 100 units per ml stains were employed: in O.lM phosphate buffer at pH 5.0 for two One per cent Alcian blue at pH 0.4 (stains hours at 60°C (specifically degrades only hya strongly sulphated glycosaminoglycans and luronic acid); chondroitinase ABC, 0.5-0.2 mucin) at pH 1.0 (stains weakly sulphated gly units per ml in O.lM Tris HCI at pH 8.0 for cosaminoglycans and mucin), and at pH 2.5 20--40 mins at 37°C (degrades chondroitin -4 (stains all mucins and glycosaminoglycans and -6 sulphate and dermatan sulphate); including hyaluronic acid, sulphated glycosa chondroitinase AC, 0.5-0.2 units per ml in minoglycans and neuraminidase-resistant sia O.lM Tris HCI at pH 7.3 for 20--40 mins at lomucin). In addition the following stains 37°C (degrades only chondroitin -4 and -6 were employed: 1% Periodic Acid Schiff sulphate, but not dermatan sulphate); neu (PAS); PAS with periodate borohydride and raminidase, 0.5 mg per ml in O.lM phosphate potassium hydroxide, PB (KOH) PAS; buffer for 18 hours at 37°C at pH 5.8 Alcian blue-PAS; High iron diamine Alcian (degrades sialomucin). blue; Hale's colloidal iron; and Saponin. Results Enzyme Studies In order to identify more accurately the pro Macroscopic Pathology teoglycans in the scleral tissue, histochemical All three enucleated globes (cases 1-3) were staining with 1 % alcian blue, pH 2.5 was com within the range of normal dimensions. The bined with prior incubation of the tissue sec retinae were detached and there was an exten tions with the following enzymes: bovine sive proteinaceous subretinal exudate, testicular hyaluronidase, 100 units per ml in particularly in cases 1 and 3. The sclera O.lM phosphate buffer pH 5.5 for two hours appeared uniformly thickened in case 3, and 362 J V FORRFSTf'R ET AI..

Fig.7a. Fig.7b.

Fig. 7. f.'feClroll microscII!'.\' ol relill()'c/lOroidaf illlerj'lcl' ill 1/1'l'al effllsion sl'lldrollle. (11) RFL cells with single farge proleill'rirh il/cil/sillll: !Jar = /() fUll. (hi Hasal i"ji,fdi"g.\ ill RI'E cells; !Jar = 5 [till. (e) Thickelling ol Hmch's 11I(,lIIl>r£ll/1' he/ol\' RI'L cells will! Fig.7c. depositioll "I dec/roll dellse I/wlerial: I",r = 5 WI/' thickened at the posterior pole in case 2. while excessive deposition of sulphated mucins in it was of normal thickness in case I. Resected the uveal effusion cases. scleral tissue from the pre-equatorial sclera in Alcian blue staining of the sclera at differ case 4 was approximately 1.5 x thickness of ent pH levels revealed some interesting find normal sclera. In cases 1-3. there was obvious ings. In the normal eye there was generally exudation in the ciliary body and ante rior weak Alcian blue staining but there was a suprachoroidal space. marked difference in staining between the pre-equatorial (anterior) sclera and the para Microscopic Pathology macular (posterior) sclera particularly at pH (A) Sclaal Pathology 2.5. This suggests that in the normal eye sul Increased quantities of PAS positive phated proteoglycans are uniformly distri material in the sclera were observed in all four buted throughout the sclera. but that cases of uveal effusion syndrome when com non-sulphated glyeosaminoglycans (such as pared to the control tissue (Fig. I). This was hyaluronal<:) and sialomucins may be concen particularly marked in the post-macular trated in the para-macular sclera. In addition. scleral tissue. Strong staining was also most of the Alcian blue-positive material was observed with Hale's colloidal iron and high located in the inner sclera. while the outer iron diamine Alcian blue. suggesting an sclera and episclera were negative. THE UVEAL EFFUSION SYNDROME AND TRANS-SCLERAL FLOW 363

In eyes with uveal effusion, there was a normal lamellar arrangement of the collagen marked increase in Alcian blue positive fibrils, numerous electron dense deposits in material (Table II; Fig. 2a, b) at all pH levels the interfibrillar spaces, and a greater varia in both anterior and posterior sclera. This sug bility in collagen fibrildiameter with a general gests that in addition to increased deposits of increase in fibril width compared to normal strong and weakly sulphated proteoglycans sclera (Fig. Sa, b). Sclera in case 4 showed (detected at pH 0.4 and 1.0 respectively) addi clumped electron dense material between col tional non-sulphated proteoglycans and sia lagen fibreswhich had an indistinct cross-ban lomucins may have been present. ding. Finely granular material was present Enzyme histochemistry of the normal eye between collagen fibrils in the control tissue. revealed a reduction in staining with Alcian blue at pH 2.5 when the tissue was treated (B) Uveoretinal Pathology with testicular hyaluronidase and chondroiti Despite the unusually massive engorge nase ABC as described in Methods (Table ment of the uveal tissue with fluid, there was IlIa, b; Fig. 3a, b). No reduction in stain was remarkably little inflammatory cell reaction. observed when the tissue was treated with Choroidal vessels showed evidence of venous streptomyces hyaluronidase and only a mini stasis and perivascular engorgement (Fig. 6), mal decrease in stain intensity was observed while the retinal pigment epithelium was after chondroitinase AC. No effect was hypertrophic and hyperplastic in foci beneath observed with neuraminidase. These results the detached retina. Many RPE cells con confirm previous biochemical studies'3,'4 that tained large PAS positive inclusion bodies. normal sclera contains little or no hyaluronate Numerous RPE cell rests were engaged in (no effect observed with streptomyces hyalu proliferation and migration into the subret ronidase) and only a small proportion of total inal space (Fig. 6) which contained very large glycosaminoglycan is comprised of chondroi amounts of a highly proteinaceous fluid. The tin -4 or -6 sulphate (partial effect with photoreceptor layer showed atrophic outer chondroitinase AC), whereas the major com segment changes with vacuolation and cell ponent is dermatan sulphate (removed by loss, while the retina showed generalised chondroitinase ABC and also removed by minor atrophic changes. broad-spectrum testicular hyaluronidase). By electron microscopy, the RPE cells The anterior sclera contains little sialic acid, showed signs of multilayering and migratory but the para-macular sclera may contain some activity while their cytoplasm was frequently neuraminidase-resistant sialic acid. engorged with single circular protein-rich In the scleral tissue from uveal effusion syn inclusions (Fig. 7a, b). Loss of transport func drome eyes, there was a similar reduction in tion in the RPE cells was suggested by the Alcian blue staining after testicular hyaluroni abnormalities in basal infoldings (Fig. 7b) and dase and chondroitinase ABC treatment, but stunting and loss of apical microvilli. How there was also a significant reduction in stain ever, tight junctions remained intact. Macro intensity after chondroitinase AC treatment phages containing large inspissated (Table lIla, b; Fig. 4a, b). Complete removal proteinaceous inclusion bodies were also of Alcian blue reactivity was not achieved identified. with the present enzyme treatments but this Bruch's membrane was considerably thick may have been a simple dose-saturation ened and dilated with interfibrillar ground effect. These results indicated that in the substances and electron dense round bodies uveal effusion syndrome, dermatan sulphate (Fig. 7c). The choroid contained a massive and chondroitin sulphate preferentially accu proteinaceous exudate in the extravascular mulated in the sclera, while no apparent accu compartment. mulation of hyaluronate (resistant to streptomyces hyaluronidase) or sialomucins (no effect with neuraminidase) was observed. Discussion Electron microscopy of scleral tissue from This review of four cases of uveal effusion syn uveal effusion cases showed disruption of the drome has led to the following observations: 364 J. V. FORRESlER ET AL.

(a) three of the four cases showed some contains varying amounts of iduronic acid degree of scleral thickness; from 95% to 10%, the remainder of the dis (b) the increase in scleral thickness was due accharides in the polymer containing glucu to accumulation of glycosaminoglycan ronic acid.IS Both dermatan sulphate and (proteoglycan) and also, in part, related chondroitin sulphate exist in the tissues bound to a variable increase in collagen fibril to a core protein as proteoglycans. Dermatan width; sulphate proteoglycan occurs as two forms, (c) the increase in glycosaminoglycan con 'small' proteodermatan (PGI) containing tent was mainly due to deposition of der large quantities of iduronic acid (up to 95%) matan sulphate, and also, but less so, to and 'large' proteodermatan (PGII) with chondroitin sulphate as revealed by about 10% iduronic acid.I7 PGn co-exists enzyme digest studies; with chondroitin sulphate proteoglycan (d) the engorged uveal tissue showed within the interfibrillar space. In contrast, a remarkably little inflammatory change; 'small' PGI combines specifically with the (e) the retinal pigment epithelium showed 'd,e' region of the banded collagen fibril in a marked changes, including foci of regular pattern, and completely encases the 16,1 proliferation. fibril. Scott and HughesI9 have shown that PGI is instrumental in regulating collagen The results therefore confirm, and extend, fibril width or thickness during development, al. the observation by Ward et that the and may be important in determining whether abnormality in scleral tissue in the uveal effu Type I collagens form part of an interstitial sion syndrome is characterised by abnormal matrix as in the dermis or whether they deposits of glycosaminoglycan and which are become specialised to form specific collagen now shown to be predominantly dermatan structures of high tensile strength such as sulphate. Gass9 further hypothesised that the occur in tendons and sclera. pathogenesis of the uveal effusion syndrome The presence of increased quantities of der was related to the abnormal deposits of glyco matan sulphate in the uveal effusion syn saminoglycans since they retarded the trans drome may therefore have some influence on cleral diffusionor flowof protein-rich fluid.In collagen fibril diameter which may account addition, due to their highly hydrophilic for the variable width and apparent increased nature the increased glycosaminoglycans bind thickness of collagen fibril observed in this increased quantities of water, which cause an study (Fig. Sa, b). increase in the intrascleral swelling pressure As noted above, these observations suggest and inhibit venous drainage through the vor an intrinsic defect in scleral fibroblast metab tex veins, thereby causing further uveal olism since these cells are the most likely engorgement. source of sclera proteoglycans. An alternative Gass' hypothesis implies therefore that possibility, however, is that the primary defect idiopathic uveal effusion syndrome repre lies in the retinal pigment epithelium since sents a primary defect in scleral fibroblastpro this layer is crucial to the active transport of duction of proteoglycans. Recent biochemical fluid across the retina to the sclera. Consider and electron microscopical studies, including able abnormalities were observed in the RPE some very elegant rotary shadowingIS and layer in this study, including loss and stunting X-ray diffractionI6 experiments, have studied of apical microvilli, protein-rich intracellular the relationship between proteoglycans and inclusions, and morphologically altered basal collagen fibrils in sclera. Both dermatan sul infoldings. These findings might indicate a phate and chondroitin sulphate are disaccha functional defect in the transport of fluid ride polymers of N-acetyl-galactosamine and across the RPE but are more likely to be either of the epimers, iduronic acid (dermatan secondary to the longstanding retinal detach sulphate) and glucuronic acid (chondroitin ment, since similar findings may be observed sulphate). Chondroitin sulphate contains no in rhegmatogenous detachments. In addition, iduronic acid, and in the tissues it is only the protein-rich subretinal exudate probably loosely associated with the collagen fibrils, acted as a stimulus for the increased phago essentially lacking the space between groups cytic, proliferative and migratory activity of of fibrils. Dermatan sulphate, in contrast, the RPE cells in uveal effusion syndrome. THE UVEAL EFFUSION SYNDROME AND TRANS-SCLERAL FLOW 365

6 Clinically, the leopard-spot pigmentary fun Wilson RS and Hanna C: Idiopathic chorioretinal effusion: an analysis of extra-cellular fluids. Ann dal changes would correspond to the foci of Ophthalmol1977,9: 647-53. RPE proliferations and multi-layering. 7 Brubakerr RF and Pederson JE: Ciliochoroidal In conclusion, therefore, this study sup detachment. Surv Ophthalmol1983, 27: 281-89. 8 ports the proposal by Gass9 that the accumu Brockhurst RJ: Vortex vein decompression for lation of scleral, choroidal and subretinal nanophthalmic uveal effusion. Arch Ophthalmol 1980,98: 1987-90. protein-rich fluid is probably due to 9 Casswell AG, Gregor ZJ, Bird AC: The surgical abnormally thickened sclera, causing management of uveal effusion syndrome. Eye increased back-venous pressure with exces 1987,1: 115-19. 0 sive transudation of fluid from the choroidal 1 Gass JDM: Uveal effusion syndrome. A new hypothesis concerning pathogenesis and tech vasculature. The increased scleral thickness is nique of surgical treatment. Retina 1983, 3: due to an accumulation of proteoglycan, 159-63. 11 specifically dermatan sulphate proteoglycan Vine AK: Uveal effusion in Hunter's syndrome. Ret ina1986, 6: 57-60. with a smaller contribution from chondroitin 12 sulphate proteoglycan. This further increases Ward RC, Gragondas ES, Pon DM, Albert DM: Abnormal scleral findingsin the uval effusion syn resistance to transcleral flow of protein-rich drome. Am J Ophthalmol1985, 106: 139-46. fluid, which increases the colloid osmotic 13 Coster L and Fransson L-A: Isolation and charac pressure of the tissues. It is likely that the terisation of dermatan sulphate proteoglycans from bovine sclera. Biochem J 1981,193: 143-53. accumulation of scleral proteoglycan is a 14 Coster L, Rosenberg LC, van der Rest M, Poole primary defect and may represent an ocular AR: The dermatan sulphate proteoglycans of form of mucopolysaccharidosis, since similar bovine sclera and their relationship to articular findings have been observed in a case of (he cartilage. J Bioi Chern1986, 262: 3809-12. systemic mucolysaccharidosis, Hunter's 15 Ward MP, Scott JE, Coster L: Dermatan sulphate 10 syndrome. proteoglycans from sclera examined by rotary shadowing and electron microscopy. Biochem J References 1987,242: 761-6. 16 1 von Graefe A: Zur diagnose des beginnenden intra Quantock AJ and Meek KM: Axial electron density ocularen Krebses. Albrecht von Graefes Arch. fur of human scleral collagen. Location of proteogly Ophthalmologie 1858,4: 2180-229. cans by X-ray diffraction. Biophys J 1988, 54: 2 Verhoff FH and Waite JH: Separation of the choroid 159-64. with report of a spontaneous case. Trans Am 17 Coster L, Rosenberg LC, van der Rest M, Poole Ophthalmol Soc 1858,23: 120-39. AR: The dermatan sulphate proteoglycans of 3 Schepens CL and Brockhurst RJ: Uveal Effusion 1. bovine sclera and their relationship to those of Clinical Picture. Arch Ophthalmol 1963, 70: articular cartilage. J Bioi Chern 1987, 262: 189-201. 3809-812. 4 Gass JDM and Jallow S: Idiopathic serous detach 18 Young RD: The ultrastructural organisation of pro ment of the choroid, ciliary body and retina (uveal teoglycans and collagen in human and rabbit effusion syndrome). Ophthalmology 1982, 89: scleral matrix. J Cell Sci1985, 74: 95-104. 1018-32. 19 Scott JE and Hughes EW: Proteoglycan collagen 5 Brockhust RJ: Nanophthalmic eyes with uveal effu relationships in developing chick and bovine ten sion. A new clinical entity. Arch Ophthalmol dons. Influence of the physiological environment. 1975,93: 1289-99. Can Tissue Res 1986, 14: 267-78.