Vitreous Synchisis and Syneresis
Vitreous degeneration is a physiologic process that occurs with age and may be accelerated in eyes with longer axial length. As the vitreous degenerates, there is liquefaction of the vitreous gel, known as “synchisis,” resulting in small pockets of liquefied vitreous within the firmer vitreous. This leads to destabilization of the vitreous and promotes its collapse, known as “syneresis.” The boundaries between each liquefied pocket and the vitreous gel may form speckled opacifications that may later manifest as symptomatic floaters. These vitreous opacities may become visible to patients and appear as spots, strings, or cobwebs, in the absence of a posterior vitreous detachment (PVD). There are four grades of physiologic vitreous degeneration as documented with swept-source OCT (SS-OCT).
Posterior Vitreous Detachment
Posterior vitreous detachment (PVD) is a common consequence of aging that occurs with vitreous degeneration. As the vitreous body shrinks with syneresis, there is separation of the vitreous cortex or posterior hyaloid from the retina. PVD may also result from traumatic eye injury or inflammatory diseases, or be induced surgically. The process of PVD may occur in stages beginning with perimacular and perifoveal PVD, followed by vitreofoveal separation with or without a break in the posterior wall of the premacular bursa and, finally, separation of the vitreous from the optic disc. Gel liquefaction without concurrent dehiscence at the vitreoretinal interface leads to anomalous PVD and its complications.
With complete separation of the vitreous from the optic disc, a Weiss ring corresponding to the site of previous attachment to the optic disc may appear as a symptomatic ring-shaped floater. The Weiss ring may take many forms as shown here or may be fragmented during the process of vitreous separation.
Asteroid hyalosis is a degenerative condition of the vitreous with a prevalence of 1.2% in adults. It is found to be more frequent with aging, with 0.2% prevalence in 43- to 54-year-old and 2.9% in 75- to 86-year-old patients. Multiple small white deposits that typically have a refractile appearance, which resemble stars (or asteroids) shining in the clear night sky, form in the vitreous. The etiology of asteroid hyalosis is still unknown. There may be an association with diabetes mellitus, hyperlipidemia, atherosclerosis, and hypertension. The asteroid bodies are mostly composed of hydroxyapatite and phospholipids. Asteroid hyalosis is unilateral in 75-90% of cases. Typically, the disorder does not produce symptoms or a reduction in visual acuity. Occasionally, patients may express symptomatic floaters. Treatment is rarely necessary, but, in highly symptomatic cases or when necessary for visualization of the fundus, a vitrectomy may be indicated.
Asteroid hyalosis should be differentiated from synchisis scintillans or cholesterosis bulbi, which is an extremely rare accumulation of cholesterol crystals in liquefied vitreous that tend to settle or gravitate inferiorly, causing a snow globe effect. Because synchisis scintillans is an end-stage degenerative condition that occurs in eyes with extensive inflammation, hemorrhage, or trauma, it is usually not visible clinically and more commonly diagnosed after enucleation by the pathologist.
Amyloidosis encompasses a group of disorders characterized by extracellular deposition of amyloid proteins in various organs and tissues of the body. At least 24 different proteins are known to be amyloidogenic; however, the most common forms are immunoglobulin light-chain (AL protein) in primary amyloidosis and serum amyloid A (AA protein) seen in chronic inflammatory diseases. Amyloid proteins consist of insoluble fibrillar aggregates arranged in a characteristic beta-pleated sheet configuration, which is responsible for the ability to bind Congo red and show birefringence in polarized light. Amyloidosis of the vitreous is a rare condition that may be primary, acquired, or familial in nature. It is more often related to familial amyloid polyneuropathy (FAP); however, it may very rarely occur sporadically.
Familial amyloid polyneuropathies (FAPs) are rare forms of amyloidosis associated with amyloid accumulation in the vitreous. FAPs are inherited in an autosomal dominant fashion with variable penetrance and are caused by mutation in the transthyretin (TTR) gene at locus 18q11.2-q12.1. Involvement of the vitreous is usually seen in association with systemic amyloidosis and clinical features including peripheral neuropathy, renal dysfunction, and cardiomyopathy. Amyloid deposition in the vitreous appears as diffuse whitish gray or yellowish material having a “cobweb” or “cotton-wool” appearance. Other fundus findings include perivascular deposits, superficial retinal gray-white deposits, and small vessel occlusions with associated angiographic filling delays on both fluorescein and indocyanine green angiography. Vitreous amyloidosis should be considered in the differential diagnosis of any vitreous opacification or haze. Diagnosis relies on clinical suspicion and staining of vitreous biopsy specimens with Congo red dye. Vitrectomy remains the treatment of choice for symptomatic vitreous opacification.
Intravitreal cysts are rare ocular curiosities that are usually found incidentally on routine ophthalmological examination. Patients may be asymptomatic or may complain of floaters or transient visual blurring. Vitreous cysts may be classified as congenital or acquired. Congenital cysts are thought to be associated with remnant hyaloid vessels and are usually nonpigmented, smooth, sessile, or pedunculated. Congenital cysts are typically located anterior to the optic disc, and may have limited movement due to vitreous strands attached to the optic disc. Acquired cysts are found in degenerative or inflammatory diseases including retinitis pigmentosa, choroidal atrophy, retinal detachment, retinoschisis, parasitic uveitis, nematode endophthalmitis, and trauma. They are usually pigmented and thought to arise from the degeneration of a ciliary body adenoma breaking into the vitreous cavity or a vitreous reaction to underlying retinal and choroidal degeneration. Vitreous cysts are benign and may be observed without treatment. Symptomatic cysts may be treated with laser photocystotomy or pars plana vitrectomy with cyst excision.
Angioid streaks are visible, irregular crack-like dehiscences in Bruch membrane that are associated with atrophic degeneration of the overlying retinal pigment epithelium. Knapp coined the term “angioid streaks” because their appearance resembles retinal vasculature. Angioid streaks are most commonly associated with pseudoxanthoma elasticum, although they may also be associated with Paget disease of the bone, Ehler–Danlos syndrome, sickle cell or thalassemia hemoglobinopathies, acromegaly, and diabetes mellitus. Patients with angioid streaks are generally asymptomatic, unless they develop complications such as traumatic Bruch membrane rupture or macular choroidal neovascularization (CNV).
Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder associated with dermatologic, gastrointestinal, cardiovascular, and ocular findings. PXE has been associated with mutations in the ABCC6 gene at chromosome 16p13.1. Characteristic skin changes typically affect the neck, axilla, and other flexural areas. Fundus findings include angioid streaks, a reticular macular dystrophy, a speckled appearance temporal to the macula known as peau d’orange, optic nerve head drusen, comet-like peripheral crystalline bodies, and peripheral RPE atrophic spots. An exudative detachment with yellowish and clear exudate between the ellipsoid zone and the retinal pigment epithelium may produce an acquired vitelliform lesion in PXE. CNV occurs in 72-86% of eyes and is often bilateral. Treatment of CNV in PXE using thermal laser photocoagulation or verteporfin photodynamic therapy is frequently complicated by recurrences and poor visual outcomes. Recently, intravitreal injections of anti-vascular endothelial growth factor drugs have shown promise in treating these patients.
A “pattern dystrophy-like” change of the macula may develop bilaterally in approximately 65% of patients with PXE and may manifest as any of the 5 subclasses of pattern dystrophy, including reticular dystrophy, fundus pulverulentus, fundus flavimaculatus, butterfly-shaped dystrophy, and vitelliform dystrophy. The pattern dystrophy-like appearance may be a combination of any of the 5 subclasses and may progress from one type to another over time. Because this condition is unrelated to the autosomal dominantly inherited pattern dystrophy first described by Sjögren, the continued use of the term “pattern dystrophy” in PXE is controversial. Clinically, it is important to recognize that PXE may appear with pattern dystrophy-like changes especially in cases in which angioid streaks are very subtle.
Subretinal Fluid and Acquired Vitelliform Lesions
Subretinal fluid unrelated to choroidal neovascularization (CNV) may occur in patients with PXE. Subretinal fluid may be found in eyes with no detectable neovascularization or in areas of the fundus remote from neovascular tissue. This form of subretinal fluid is clinically more subtle than the exudation seen with neovascular tissue. The subretinal fluid is thought to accumulate due to RPE dysfunction preceding RPE cell death. It is typically stable over time and shows no change with intravitreal anti-VEGF therapy.
Patients with PXE are susceptible to intraocular hemorrhages secondary to traumatic rupture of the RPE, Bruch membrane, and choroid. This could be the result of an intrinsic weakness of the Bruch membrane or an associated clotting abnormality in PXE. Patients may present with subretinal or intraretinal hemorrhages overlying the rupture line, which often develop concentric to the disc or, less frequently, in a radial pattern. In time, the hemorrhages clear and may leave a fibrotic scar. The area with the break in the Bruch membrane is at high risk for CNV.
Pathologic or degenerative myopia is a leading cause of visual impairment worldwide. It is most common in Asia where the prevalence may be more than 10% in certain populations. Although there is no standardized definition, the commonly used criteria include spherical refractive error in excess of −6 D and axial length of greater than 26.5 mm. This entity has been linked to genetic, environmental, and socioeconomic risk factors.
Myopic macular degeneration, often associated with a posterior staphyloma, consists of progressive thinning of the retinal pigment epithelium and choroid, fine yellowish-white breaks in Bruch membrane known as lacquer cracks, subretinal hemorrhages, and secondary CNV. Additional ocular findings in pathologic myopia include macular hole, macular retinoschisis, vitreoretinal interface disturbances, premature PVD, peripheral retinal degeneration, retinal detachment, cataract, and normal-tension glaucoma.
Staphyloma is defined as an outpouching of the ocular wall, the radius of which is less than the surrounding curvature of the globe. The number and location of staphylomas may vary in each eye. Curtin’s original classification of staphyloma subtypes used ophthalmoscopic findings and was based on the morphology of irregularities within the staphyloma. However, the advent of OCT imaging has allowed precise visualization of all staphylomatous irregularities within the globe and has resulted in the formulation of a new classification that is based on the morphology of the outermost border of the staphyloma. Staphylomas are now divided into five subtypes.
Radial Tracts and Myopic Staphyloma
A linear or leaf-like emanation that arises from the posterior edge of the staphyloma is seen in approximately 8% of eyes with a myopic posterior staphyloma. As illustrated in the case below, these tracts (yellow arrows) demonstrate clinical features that are comparable to descending tracts in central serous chorioretinopathy; however, they commonly have an anti-gravity orientation. They are proposed to represent sites of previous or existing serous retinal detachment due to RPE injury at the abrupt edge of the staphyloma. The changes in globe curvature are best appreciated on three-dimensional MRI images. OCT images of these regions often demonstrate outer retinal and RPE disruption. (The orientation and site of OCT imaging is represented by the blue arrow.)
Dome-shaped macula (DSM) is a morphological feature recently described using OCT. This entity is characterized by an inward convexity of the macula that, in the majority of cases, is associated with high myopia, but can also be found in eyes with hypermetropia, inherited retinal dystrophies, and central serous chorioretinopathy. The cause is unknown although it is postulated to be related to a localized increase in scleral thickness in the area of the DSM and could be due to the process of ocular expansion in myopia. Macular complications of DSM include CNV in 12% of eyes. Localized serous macular detachment without CNV is found in up to 44% of eyes at the top of the DSM, possibly due to choroidal outflow obstruction by a thick sclera and/or abrupt changes in choroidal thickness. Extrafoveal schisis is found in 18%; however, foveal schisis is uncommon suggesting that DSM may be protective against the development of foveal schisis.
Myopic Macular Degeneration
Patients with pathologic myopia may develop severe vision loss from retinal atrophy and CNV. These changes commonly occur in the central macula within a posterior staphyloma. The atrophy progresses insidiously whereas the neovascularization and resulting disciform scarring may produce sudden loss of central vision.
Myopic retinoschisis, also known as myopic traction maculopathy, is characterized by retinoschisis of the posterior retina and occurs in 9-34% of highly myopic patients with posterior staphyloma. The pathogenesis is multifactorial involving tangential traction of the inner retina, rigidity of the internal limiting membrane (ILM), thinning of the retina, traction of retinal vessels, and progression of posterior staphyloma. The natural course in a majority of patients can be considered as generally stable with some patients progressing to macular hole formation with or without retinal detachment. Treatment usually involves vitrectomy with ILM peeling and gas tamponade. Although recurrences of myopic retinoschisis may occur, outcomes following repeat vitrectomy can still be favorable.
Lacquer cracks refer to breaks in the RPE-Bruch membrane complex and have a prevalence of 4-9% in highly myopic eyes. Choroidal and scleral stretching, due to increasing axial length, is the postulated mechanism for these lesions. They are more commonly seen in the posterior pole within the posterior staphyloma, but can also be found in the mid-peripheral or peripheral retina. Lacquer cracks may be precursors to myopic CNV and patchy chorioretinal atrophy. They may also be associated with subretinal hemorrhage, in the absence of CNV, due to bleeding from the choriocapillaris.
Myopic Stretch Lines
Myopic stretch lines are irregular, branching lines found in the posterior fundus of highly myopic eyes and should be differentiated from lacquer cracks. Myopic stretch lines appear hypofluorescent with ICG angiography similar to lacquer cracks. They can be distinguished however by their pigmented brown appearance on ophthalmoscopy, hyperautofluorescence with fundus autofluorescence, and hypofluorescence on fluorescein angiography. Myopic stretch lines are thought to represent retinal pigment epithelium under stress and may be precursors to lacquer cracks.
Patients with pathologic myopia may experience subretinal hemorrhages either from CNV or due to extension of the posterior staphyloma with bleeding from the choriocapillaris. Both types of hemorrhages often coincide with lacquer cracks.
The prevalence of myopic CNV in pathologic myopia is between 5-11% and is bilateral in approximately 15% of patients. Features associated with an increased risk of myopic CNV include lacquer cracks, patchy atrophy, thinning of the choriocapillaris and choroid, and CNV in the fellow eye. Type 2 neovascularization is the most common manifestation of proliferating choroidal vessels in myopic macular degeneration. The neovascularized membrane is usually pigmented and is often seen in association with a margin of hemorrhage. It usually develops at a discernible lacquer crack, although this is sometimes not evident clinically. As the CNV regresses, a fibrous pigmented scar sometimes referred to as Fuchs spot, or Forster-Fuchs spot, may form and eventually become surrounded by atrophy. Importantly, myopic CNV must be distinguished from other forms of CNV, in particular, multifocal choroiditis or punctate inner choroidopathy, which tend to occur in myopes as well.