30 Exudative and Tractional Retinal Detachments
Exudative retinal detachment refers to separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) due to abnormalities of the normal hydrostatic/osmotic pressure gradients or transport mechanisms that maintain the physical apposition of these two tissue layers or to excessive production of extracellular fluid. In contrast, tractional retinal detachment refers to separation of these tissue layers secondary to anatomically recognizable forces that physically pull on the retina. Importantly, neither type of retinal detachment is associated with retinal breaks. The common clinical features, pathogenesis, and differential diagnosis of exudative and tractional detachments are discussed later. Those entities not covered elsewhere in this book are presented in greater detail in this chapter.
30.2 Exudative Retinal Detachments
30.2.1 Clinical Features
Exudative or “serous” retinal detachments are characterized by separation of the neurosensory retina and RPE without the presence of a retinal break or vitreoretinal traction. They can be further differentiated from rhegmatogenous detachments by the lack of retinal folds or rugae on their surface (Fig. 30-1). Exudative detachments can develop in all age groups when defects occur in the normal mechanisms for clearance of subretinal fluid or when these mechanisms are overwhelmed by excessive exudation. Such abnormalities are seen in a variety of disease states involving the RPE, Bruch’s membrane, choroidal vasculature, or the retina. Exudative detachments display a dome or convex configuration, and their lateral extent can vary greatly, from a few disc diameters to the entire retina. The height of the detachment can likewise vary, and in some severe cases, the retina may be visible just posterior to the lens (Fig. 30-2). In large exudative detachments, the subretinal fluid may shift to dependent areas of the fundus with changes in the patient’s head position. Exudative detachments of the retina frequently coexist with detachments of the choroid.
Patients present with a history of decreased visual acuity, visual field defects, metamorphopsia, or floaters. Photopsia may be present as well, but when this history is elicited, patients should be examined carefully for the presence of a retinal break. The visual acuity depends on the chronicity and extent of the detachment as well as associated RPE and choroidal derangements. Visual acuity can vary from 20/20 in cases of central serous chorioretinopathy (CSC) to count fingers or worse in age-related macular degeneration with massive exudative detachment. The intraocular pressure can be decreased in the presence of ciliary body inflammation or detachment but is often normal. The anterior segment examination will frequently reveal clues to the diagnosis, such as conjunctival and episcleral injection in scleritis or anterior chamber cell and flare in Vogt–Koyanagi–Harada (VKH) syndrome. Fundus examination demonstrates single or multiple dome-shaped retinal elevations, with larger detachments exhibiting the phenomenon of shifting subretinal fluid.
Fluorescein angiography can be instrumental in diagnosis if the subretinal fluid is clear and the detachment is not too bullous. Fluorescein angiography may demonstrate small foci of hyperfluorescence in cases of CSC or characteristic patterns of lacy hyperfluorescence in choroidal neovascularization from a variety of causes. It can also help confirm various characteristic vascular changes of retinal diseases that can lead to exudative retinal detachments, such as leakage from macroaneurysms in Coats’ disease. In certain diseases, fluorescein angiography can be used to guide laser photocoagulation therapy. Indocyanine green (ICG) angiography may be useful in showing areas of increased choroidal vascular permeability in CSC or hyperfluorescent nodules with late hypofluorescence in polypoidal choroidal vasculopathy. Ocular coherence tomography (OCT) can show subretinal fluid and cysts in choroidal neovascularization and, with enhanced depth imaging (EDI), can be instrumental in making the diagnosis of CSC if the choroidal layer is thickened. Ultrasonography is helpful in eyes with both hazy and clear media. It may reveal the presence, location, and size of intraocular tumors; show scleral or choroidal thickening in inflammatory disorders; and display any coexisting choroidal detachment. Computed tomography (CT) or magnetic resonance imaging (MRI) can provide similar information in cases in which an ultrasound examination cannot be performed because of lack of patient cooperation (e.g., in a child) or because pressure from the ultrasound probe has potential for damage to the eye (e.g., in posttraumatic cases). Finally, CT or MRI can help with diagnosis of orbital and intracranial disorders (e.g., arteriovenous fistulas), which can occasionally manifest secondary exudative detachments.
30.2.2 Differential Diagnosis
This chapter will focus on entities capable of causing extensive exudative retinal detachments extending beyond the macula. The differential diagnosis of exudative retinal detachment is summarized below.
Conditions Causing Exudative Retinal Detachments
Central serous chorioretinopathy
Idiopathic uveal effusion/nanophthalmos
Surgical or postsurgical
Benign reactive lymphoid hyperplasia
Disseminated intravascular coagulation
Toxemia of pregnancy
Thrombotic thrombocytopenic purpura
Collagen vascular disease (systemic lupus erythematosis)
Granulomatosis with polyangiitis (Wegener’s granulomatosis)
Choroidal neovascularization (any cause)
Retinopathy of prematurity
Familial exudative vitreoretinopathy
Arteriovenous fistula/carotid obstruction
Retinal vein occlusion
Bilateral diffuse uveal melanocytic proliferation
Abbreviation: HELLP, hemolysis, elevated liver enzymes, low platelets.
The mechanisms responsible for maintaining a fluid-free subretinal space are numerous and complex. Intraocular hydrostatic pressure, osmotic pressure from choroidal extracellular protein, the interphotoreceptor matrix, and metabolic fluid transport by the RPE are all thought to play a role. 1 Tight junctions between RPE cells, which combine to form the outer blood–retinal barrier, provide high resistance to osmotic fluid flow across the retina. Without breakdown of this barrier, experiments have shown that RPE-mediated fluid transport is the predominant mechanism for deturgescence of the subretinal space. 1 With focal damage to this barrier, fluid is eliminated according to oncotic pressure gradients, 1 , 2 which promote fluid egress from the subretinal space due to high protein concentration of the choroid.
Spitznas 3 and Marmor 4 have hypothesized that a widespread deficit in RPE transport function is necessary to generate and maintain an exudative retinal detachment. In affected patients, the diseased RPE cells are barely able to prevent a detachment in their resting state, and when confronted with excess stress (e.g., ischemia), the system is overwhelmed and a detachment results. A small RPE defect (as often noted in patients with CSC) may be needed to provide a source of subretinal fluid entry. However, a serous detachment may be maintained only in the setting of diseased remaining RPE cells unable to prevent detachment yet still present to prevent fluid egress by oncotic pressure gradients that work in the absence of intact RPE. 5 In addition, inflammatory subretinal fluid may have increased protein content, reducing the oncotic pressure gradient between the subretinal space and the choroid. 2
Widespread RPE damage may explain several etiologies of exudative retinal detachment, but some disease states, such as disseminated intravascular coagulation and hypertension, appear primarily to affect blood flow of the choroidal vasculature. Experimental serous retinal detachments have been created by using rose bengal as a photosensitizer to damage retinal and choroidal vessels selectively. 6 These detachments can be created with choroidal occlusion as well as lesser focal damage to endothelial cells of the choriocapillaris, resulting in increased permeability. Marmor and Yao argue that three conditions are needed for exudative detachment formation: a source of subretinal fluid entry (likely from the choriocapillaris); a blood–retinal barrier defect allowing fluid to reach the subretinal space; and impaired fluid transport or a high fluid entry rate that overwhelms normal transport mechanisms. 7
30.2.4 Specific Entities
Central Serous Chorioretinopathy
The typical patient with CSC is a man in his third to fifth decade of life with a unilateral visual disturbance and a localized exudative detachment of the neurosensory retina (and sometimes RPE) in the macula. Fluorescein angiography is instrumental in establishing the diagnosis. Characteristically, it shows a pinpoint focus of dye leakage at the level of the RPE under or near the detached retina. ICG angiography may be helpful in differentiating CSC from choroidal neovascularization and typically reveals midphase inner choroid staining that fades late in the study. 8 OCT images with EDI show a thickened choroid in the affected and the fellow eye in many cases. Most cases resolve spontaneously by 4 to 6 months, usually with good recovery of visual function, although over half of patients experience recurrent disease. 9 Cases that are chronic, recurrent, or bilateral may benefit from photodynamic therapy to facilitate subretinal fluid resorption and to improve visual outcomes. 10 Early photodynamic therapy may also be beneficial for acute CSC. 11 Laser photocoagulation directed to the area of leakage on fluorescein angiography may cause fluid resorption in refractory cases, although it may result in choroidal neovascularization and scotomas. 12 , 13 Potential roles for mineralocorticoid receptor antagonists have been explored. 14
The fluorescein leakage spot in CSC may be located in the superior fundus, distant from the fluid in the macula. The fluorescein angiogram should, therefore, include views of the superior paramacular region and midperiphery to establish the diagnosis if no leakage site is seen in the macula.
Rarely, CSC may present with large, bullous, and sometimes bilateral exudative retinal detachments. 15 , 16 Misdiagnosis as VKH syndrome, uveal effusion, leukemia, or choroidal tumor can occur. Some cases have been presumed to be rhegmatogenous and have undergone unsuccessful and unnecessary surgery. 15 Many early cases were treated with systemic corticosteroids for serous macular detachments consistent with typical CSC, and widespread bullous detachments with whitish subretinal exudate subsequently developed. It is now known that corticosteroid use is contraindicated in CSC because of its association with more severe and recurrent disease. 17 , 18 Steroid use may increase the permeability of the choriocapillaris to larger proteins.
Because steroid use and surgery are contraindicated in any form of CSC, accurate diagnosis is essential. As noted earlier, the differential diagnosis of the “bullous” variant of CSC includes VKH syndrome, choroidal tumors, and uveal effusion syndrome (UES). VKH syndrome occurs in patients with dark skin pigmentation and usually is associated with systemic symptoms, such as headache, malaise, nausea, and vomiting, before onset of visual symptoms. Vitreous and anterior chamber cells are characteristically present. The presence of an inflamed optic nerve head, choroidal thickening, or cerebrospinal fluid pleocytosis favors the diagnosis of VKH syndrome. Furthermore, the serous detachments in VKH syndrome are not associated with RPE detachments, as is common with CSC. Choroidal tumors can usually be diagnosed by fundus appearance and ultrasound examination. UES displays ciliochoroidal edema and detachment on ultrasound and exhibits prominent shifting of subretinal fluid. For difficult cases, fluorescein angiography, ICG angiography, and ultrasonography should be performed to rule out other etiologies before the institution of any therapeutic measure.
Both endogenous and exogenous corticosteroids are associated with initiation, exacerbation, and prolongation of CSC. 19 CSC is also associated with increased stress, organ transplantation, pregnancy, steroid use, and hemodialysis, all known to increase cortisol levels. 20 , 21 , 22 Several studies have documented hyperpermeable choroidal circulation in the area of RPE detachment, and steroid use or elevated cortisol may increase this effect. 8 , 23 The mechanism by which corticosteroids contribute to CSC remains unclear, and intraocular steroid administration is only rarely associated with CSC development. 24 (See ¦Chapter 16¦ for a more detailed discussion of the diagnosis and treatment of CSC.)
Uveal Effusion Syndrome/Nanophthalmos
The spontaneous development of peripheral choroidal and retinal detachments in middle-aged hyperopic patients is the hallmark of the UES. 25 UES is idiopathic and a diagnosis of exclusion, as similar findings may be caused by surgery, trauma, scleritis, or pars planitis. 26 Patients usually present with complaints of gradual loss of the superior visual field due to dependent shifting of subretinal fluid, although fluid may also be submacular, causing central vision loss. Episcleral vessel dilation and vitreous cells are frequently present, and the intraocular pressure is usually normal. Fundus examination reveals a combined exudative retinal and choroidal detachment with shifting subretinal fluid. A pattern of RPE hyperplasia with fluorescein angiographic transmission defects can be seen during or after resolution of long-standing detachments. Ultrasonography demonstrates peripheral detachments as well as choroidal thickening and decreased axial length in some patients. The syndrome is not inflammatory and does not respond to corticosteroid therapy. Analysis of subretinal fluid reveals markedly elevated protein levels, up to three times that of serum. 27 The augmented protein content produces the marked shifting of subretinal fluid seen in this condition.
Nanophthalmos is a rare bilateral disorder characterized by a small eye with a small cornea, shallow anterior chamber, high lens-to-eye ratio, thick sclera, and predisposition to uveal effusion. 26 , 28 , 29 Angle-closure glaucoma often occurs as a consequence of the crowded anterior segment. Historically, surgical manipulations for glaucoma and cataract were fraught with complications that included spontaneous retinochoroidal detachments.
In both UES and nanophthalmos, exudative detachment is caused by atypically thick sclera causing vortex vein compression, elevated choroidal venous pressure, and diminished outflow. 30 Sclera from UES patients displays abnormal deposition of glycosaminoglycans, which likely impedes fluid flow and increases scleral thickness. The finding of uveal effusion in Hunter’s syndrome supports the idea that abnormal scleral glycosaminoglycan deposition is responsible for the clinical syndrome.
In both the UES and nanophthalmos, the pathogenesis of exudative detachment is related to atypically thick sclera with possible compression of the vortex veins resulting in diminished transscleral and choroidal venous outflow.
The uveal effusions can be treated effectively with both vortex vein decompression and scleral resection. 31 These operations decompress the engorged choroid and provide surface area for fluid transport. Scleral resection away from the vortex veins is less technically challenging and results in fewer complications. The use of topical mitomycin C along with creation of a scleral window has been described. 32 Modern techniques such as phacoemulsification have greatly reduced the risk of surgical complications from cataract extraction in these patients, although such procedures continue to be high risk. 33
Exudative retinal detachments and uveal effusions may occur following a wide variety of surgical procedures. Significant hypotony following an intraocular procedure can lead to serous choroidal detachment up to several months after surgery, often associated with an overlying exudative retinal detachment. 34 , 35 A postoperative exudative retinal detachment without choroidal detachment is unusual. The term expulsive choroidal detachment refers to massive serous or hemorrhagic choroidal detachments during intraocular surgery that cause loss or prolapse of intraocular contents, such as vitreous and uveal tissue. 36 This tends to occur in patients with increased choroidal venous pressure with Valsalva maneuvers (e.g., coughing) during the operation or in patients with risk factors such as glaucoma, myopia, advanced age, hypertension, and arteriosclerosis (see ¦Chapter 35¦).
Exudative retinal and choroidal detachments can occur after any intraocular procedure but most commonly follow scleral buckling procedures. In such cases, they may be related to prolonged hypotony from subretinal fluid drainage, compression of vortex veins by the encircling band causing elevated choroidal venous pressure, damage to choroidal vasculature by cryotherapy or photocoagulation, or by creation of scleral slits to allow for passage of the scleral buckle in cases in which the buckle is not sewn in. 37 Aggressive panretinal photocoagulation can also lead to uveal effusion and exudative retinal detachment and may even cause anterior chamber shallowing or angle-closure glaucoma from anterior ciliary body rotation. 38 Both laser and cryotherapy cause thermal damage, leading to inflammation, choroidal vascular damage, and breakdown of the blood–retinal barrier.
Pain and decreased visual acuity or visual field loss are the classic presenting symptoms of posterior scleritis. The level of pain is consistent with the amount of anterior scleritis and may be absent if this is minimal. 39 , 40 Ocular findings may include anterior chamber cells, optic disc edema, choroidal detachment with surrounding folds, and serous retinal detachment (Fig. 30-3). The choroidal lesion may simulate a mass, and misdiagnosis of choroidal melanoma, metastatic carcinoma, choroidal hemangioma, or benign reactive lymphoid hyperplasia (BRLH) can occur. 41 , 42 , 43 Inaccurate diagnosis has unfortunately led to enucleation in a few cases.
Fluorescein angiography displays mottled early fluorescence, with multiple pinpoint spots of leakage at the level of the RPE in the middle phases and intense late staining of the exudative retinal detachment (Fig. 30.3). The ultrasonogram is the most helpful diagnostic test. 42 , 44 The B-scan reveals significant sclerochoroidal thickening with overlying retinal detachment (Fig. 30-4). Retrobulbar edema is often seen as an echolucency behind the area of choroidal inflammation. Optic disc swelling and a distended optic nerve sheath may be noted. The A-scan demonstrates high reflectivity of any discrete mass-like formation that may be present. These combined findings are virtually pathognomonic for posterior scleritis.
Posterior scleritis is often associated with a systemic illness, such as rheumatoid arthritis, granulomatosis with angiitis (Wegener’s granulomatosis), systemic vasculitis, systemic lymphoma, or multiple myeloma. 41 , 45 In other cases, infectious etiologies such as herpes zoster or toxoplasmosis may play a role. Many cases are idiopathic. Treatment for noninfectious disease typically begins with oral nonsteroidal anti-inflammatory drugs or oral corticosteroids. Other options include immunomodulatory therapy (e.g., methotrexate). Refractory cases may be treated with tumor necrosis factor antagonists (e.g., infliximab). 45