The Vitreous: Everyday Clinical Challenges

Introduction

• The vitreous body, ominously called “vile jelly” by Shakespeare, has been of therapeutic interest since ancient times
• According to Eber’s papyrus (1400 BC), the Egyptians thought that the inner part of the eye communicated by a canalicular system with the inner ear cavities and the lacrimal cavity
• The Egyptians hoped to restore lost vision by replacing the inner part of the eye with a lyophilized mixture injected into the inner ear

Ancient Egyptian

• Eber’s papyrus states that the best mixture to replace the vitreous was also a remedy for total blindness:
• “extract of pig’s eye humour 1 part,
• genuine Galenos 1 part,
• yellow ochre 1 part,
• fermented honey 1 part”
• Today, the vitreous is known to provide an optically clear medium, a mechanical buffer, and a nutrient tissue

Vitreous anatomy

• Ophthalmoscopically transparent but structure can be observed with slit lamp
• Rule of “4’s”
  • 4 grams
  • 4 cc
  • Occupies 4/5 of the globe
  • 4 x as viscous as water at birth
• Consistency similar too the albumin of an egg

Vitreoretinal interface

• The cortex is composed of two parts;
  • anterior cortex/anterior hyaloid face, begins about 1.5 mm anterior to the ora serrata
  • Daicker likened this structure to Velcro – this explains the strong vitreoretinal attachment at this site
  • posterior cortex/hyaloid – 100-110 µm thick and consists of densely packed collagen fibrils.
  • Hogan demonstrated that just posterior to the ora, heavy bundles of vitreous fibrils attach to the basal lamina of retinal glial cells (Müller Cells)
• There is no cortex over the disk, and the cortex is thin over the macula and fibers are more spread out

Vitreoretinal interface – Hyaloid and ILM

• The cortex/hyaloid is firmly attached to the ILM of the retina at the vitreous
  base, around the disc (Weiss ring), at the vessels, and the foveola at a
  diameter of 500 µm
• The ILM is 1 – 3 µm thick, consisting
  mainly of type IV collagen and proteoglycans.
• The ILM can be considered the basal lamina of the Müller cells
• The only region not adjacent to a basal lamina/ILM is the anterior vitreous cortex annulus that is directly exposed to the zonule and the aqueous humour of the posterior chamber
• Balazs has stated that the basal lamina/ILM prevents the passage of molecules larger than 15-20 nm and proposed that the complex of the posterior vitreous cortex and ILM could thus act as a “molecular sieve”

Vitreoretinal interface – Hyaloid and ILM

• Reeser and Aaberg consider the posterior vitreous cortex as the “metabolic center” of the vitreous because of the presence of hyalocytes embedded within the cortex
• Hyalocytes synthesize HA, matrix glycosaminoglycans and glycoproteins
• Hyalocytes become phagocytic cells in response to noxious stimuli and inflammation

Clinical relevance

• The vitreous is most firmly attached at the vitreous base, the disk, and the macula, and over retinal blood vessels particularly in the fundus periphery
• With typical vitreous detachment, the vitreous detaches everywhere except where the stronger anatomical adhesions are present
• This may result in retinal detachment
• Once a PVD occurs, the normal holes that exist in the cortical vitreous – at the macula and disc, permit the liquefied vitreous to escape into the sub-hyaloid space.
• This collapses the vitreous cortex, accelerating its further detachment from the retina up to the posterior border of the vitreous base

Vitreous examination

Because of its relative transparency and low reflectivity, the vitreous is a difficult structure to study

Vitreous examination by optical means is based mainly on observation of the Tyndall phenomenon, which is caused by the scattering of light by particles in transparent media

This examination must be carried out in an optical section using a well-focused narrow slit beam and a good quality (low distortion and wide field of view) pre-corneal lens

The light should form a sharp and bright slit, and make as large an angle as possible with the slit-lamp

Vitreous examination – Mydriasis

• Full mydriasis and clear ocular media are also of prime importance for adequate vitreous examination – Cyclomydril rather than Mydriacyl?
• Retro-illumination is useful in detecting particles in the vitreous cavity and on the inner retinal surface, as well as new vessels on the inner retinal surface, and minimal vitreous detachment
• To enhance the Tyndall effect and the visibility of fine details in the vitreous cavity, a strong source of blue or green monochromatic light can be used

Dynamic and static examination

• Dynamic examination is performed by asking the patient to look rapidly up, down, left or right, then back to the primary position of gaze
• These movements disturb the configuration of the vitreous body, which continues to move after the eyeball has become stationary – particles suspended in the inferior vitreous become visible

Binocular indirect ophthalmoscopy

• Image is real, inverted and laterally reversed
• Requires lots of skill to use
• Expensive – R30K without the required fundus lenses
• Options from 15D, 20D, 30D, and 40D fundus lenses which provide different levels of magnification
• Can use with scleral indentation

Goldmann 3 Mirror lens

• The Goldmann three-mirror contact lens neutralizes the refractive power of the cornea, allowing examination of the entire vitreous cavity
• The central portion of the lens offers a 30° upright/erect view of the posterior vitreous and of the retina
• The equatorial and peripheral mirrors are used to examine the peripheral vitreous cavity and retina from 30° to the equator and from the equatorial area to the ora serrata respectively
• The view in the mirror is inverted/upside down but not laterally reversed

Volk Super Quad 160

• Contact lens with low magnification and large field of view
• Image is real and inverted/upside down
• Can view the entire fundus up to the ora serrata
• Relatively inexpensive – $1000
• Requires some skill to use

Volk Super field

• Non contact lens with relatively large field of view
• Image is real, inverted and laterally reversed
• Inexpensive – $500
• Easy to use

Posterior segment OCT

• Spectral-domain OCT (SD- OCT) technology allows better visualization of the posterior cortex/hyaloid/ILM/retina and a more detailed image of its structure than other technology
• Limited to the macular region and disc, little value to examine the peripheral retina
• Very expensive technology but worth the investment as it has multiple functions in practice

Table 1. Types of Cells Found in the Anterior Vitreous and their Clinical
implications

• When red/brown cells are found following an acute PVD, there’s nearly a 100% correlation with retinal tears
• If Schafer’s sign is present, the likelihood of an associated retinal tear is 52 x higher than in cases where there is absence of these signs
• 25% to 90% of retinal tears are expected to proceed to a retinal detachment, missing this warning sign could put your patient’s vision in grave danger
• White, or non-pigmented, cells in the anterior vitreous may indicate an inflammatory condition

White without pressure

• Distinctive white appearance of the peripheral retina without indentation
• Whiter than the retina in white with pressure and the choroidal markings are almost obscured
• Whiteness further accentuated if scleral depression done
• Margins are sharply demarcated from normal retina
• Intervening patches of normal retina should not be confused with retinal holes
• Exact cause is unknown;
  • one school of thought states it to be a manifestation of peripheral vitreous traction while one believes it to be simply an abnormal reflex from a structurally normal VR interface
• Frequently causes confusion with subclinical RD and Retinoschisis but indentation clearly reveals that retina is still apposed to the RPE

White with pressure

• Distinctive milky white or opalescent appearance of the peripheral retina that is observed in many normal eyes when examined with scleral depression
• Retina appears normal without depression
• It is common and seen in around 30 to 35% of eyes examined with scleral depression
• Inferonasal quadrant least likely to be affected
• Incidence increases with age, no sex predilection
• Benign condition not associated with retinal breaks – associated with strong vitreoretinal adhesions
• Must be carefully distinguished from a subclinical peripheral RD

B-Scan and PVD

• PVD is more mobile than RD
• A-scan spike is higher in RD than PVD
• PVD is more prominent with higher gain settings while RD remains prominent with low gain settings
• PVD membrane has more uniform thickness than RD
• PVD variable attachment at the disc
• RD always attached at the disc

Development of rhegmatogenous retinal detachment – RRD

• Fluid vitreous is indispensable to the development of retinal detachment
• Fluid vitreous must be able to reach freely the area of a retinal break in the subhyaloid space either through the anatomical holes that exist in the vitreous cortex in front of the macula and disc, or through a tear in the cortical vitreous

A & B-Scan of RD

• Total funnel shaped RD attached at the disc
• B-Scan with low (49dB) gain setting
• A-Scan shows 100% peak corresponding to RD S – sclera, V – vitreous, R – retina,

The upper/superior temporal quadrant is the most common site for retinal break formation and should be examined in detail if a break is not readily detected

Posterior hyaloid membrane detachment – PHMD and Vitreomacular adhesion – VMA

• The diagnosis of VMA is applied to patients who have incomplete separation of the posterior vitreous with persistent attachment to the macula
• In the past, VMA has been classified by symptomatic patients versus asymptomatic patients (i.e., based on a patient’s visual complaints)
• With the introduction of OCT, physicians have become aware that VMA is a more common entity than was previously clinically known and may be part of the normal formation of PVD

VMA

• Vitreomacular adhesion is typically asymptomatic and non-pathologic, and does not cause any apparent retinal changes
• It is a natural component of the development of a PVD and can therefore be considered an incomplete PVD
• Vitreomacular adhesion, although asymptomatic, has been hypothesized as playing a role in the pathogenesis of many macular conditions such as neovascular ARMD, macular hole, and diabetic macular edema

Vitreomacular traction – VMT

• In abnormal vitreous adhesion, there can be excessive traction on the macula from the vitreous that changes the contour of the foveal surface
• There may be a distortion of the fovea, a blunted foveal reflex, cystic changes, or (in severe cases) subretinal fluid
• OCT may be the only feature that distinguishes VMT from focal VMA when the retinal anatomy is otherwise normal
• In addition, there may be elevation of the retina at the fovea at the level of the RPE
• The combination of anatomical changes on OCT with signs of perifoveolar PVD constitutes a diagnosis of VMT
• VMT can be associated with thickening of the macula, vascular leakage on FA, macular schisis, and CME
• The anatomical changes to the fovea induced by VMT can lead to reduced BVA, metamorphopsia, and micropsia

Macular hole FTMH

• A full-thickness macular hole (FTMH) is a full thickness defect in the fovea, and includes the complete interruption of all neural retinal layers from the ILM to the RPE
• Anteroposterior traction, secondary to abnormal vitreoretinal attachment at the fovea, and tangential contraction of the perifoveal vitreous cortex may be responsible for the development of macular holes

Lamellar macular hole – LMH

• In 1975, Gass described a lamellar hole as a macular lesion resulting from cystoid macular edema
• A lamellar macular hole (LMH) is now known as a partial thickness foveal defect; however, there is no universally accepted definition of lamellar macular holes
• Many believe they arise from incomplete full-thickness macular hole formation
• ERMs are commonly associated with eyes that have lamellar macular holes.
• The pathogenesis, configuration, and progression of lamellar macular holes are therefore believed to be affected by tangential retinal traction due to ERM contraction

Vitreous opacities

Failure of the hyaloid system to regress

• Mittendorf’s dot
• Muscae volitantes
• Persistent hyaloid system
• Bergmeister’s papilla

Degenerative vitreous changes

• Asteroid hyalosis
• Cholesterosis bulbi/synchesis scintillans
• Amyloidosis of the vitreous

Mittendorf dot

• Prominent fibro-vascular plaque on the posterior surface of the lens, slightly inferior and nasal to the visual axis
• Original site of communication of the hyaloid artery to the tunica vasculosa lentis
• Generally, it is a small dot on the posterior capsule, occasionally with a small strand of residual anterior
  hyaloid attached to it Muscae Volitantes Persistence of the vasa hyaloidea propria with multiple small remnants may lead to symptoms of floaters or “muscae volitantes”

Muscae Volitantes

• Persistence of the vasa hyaloidea propria with multiple small remnants may lead to symptoms of floaters or “muscae volitantes

Persistent hyaloid system

• Persistence of only the anterior part of the hyaloid artery may occur with a residual vessel attached to the posterior surface of the lens, usually inferior and nasal to the lens center
• Persistence of the posterior portion of the hyaloid artery, which is the last part of the hyaloid system to regress during fetal development, occurs in 95% of premature infants and 3% of full term infant with a variable amount of associated fibrous or glial tissue

Bergmeister’s papilla

• Bergmeister’s papilla, a common embryonic remnant, may represent both deficient atrophy of glial tissue and glial overgrowth normally located at the optic disc

Asteroid hyalosis

• Striking clinical appearance of glistening, yellowish white, spherical bodies suspended throughout the vitreous
• The asteroid bodies are variable in size and do not appear to be affected by gravity
• Vitreous gel shows little or no evidence of liquefaction surrounding these particles
• The patient is usually completely asymptomatic, with no decrease in visual acuity
• Complex lipid and calcium phosphorus composition

Synchesis scintillans/Cholester osis bulbi

• Synchesis scintillans crystals are cholesterol crystals
• More appropriate term for synchesis scintillans is cholesterosis bulbi
• The exact aetiology of the cholesterol crystals in cholesterosis bulbi is uncertain

Amyloidosis of the vitreous

• Amyloidosis is a disease caused by localized or generalized deposition of an abnormal protein in the body
• Opacification of the vitreous caused by amyloid is an uncommon and often misdiagnosed condition that causes progressive visual loss
• The process is usually associated with primary familial systemic amyloidosis
• Ocular involvement was found in 8% of cases of familial amyloidosis but the incidence may be higher

Lattice degeneration

• Progressive lattice like degeneration seems to result from insufficiency of the retinal circulation or from other factors markedly affecting the inner retinal layers and the vitreous cortex.
• The affected retina is thin and degenerated, and a vitreous condensation of variable thickness is attached to the anterior and posterior edges of the lattice
• The membrane contains vitreous fibers that seem to exert traction on the edges of the lattice like degeneration
• Lattice like degeneration affects the retina, the cortical vitreous, and the choroid
• The zone involved is especially prone to develop retinal breaks – round holes
• The condition is usually bilateral, and it is found predominantly in myopic eyes
• It is characterized by retinal thinning, variable pigmentation, and choroidal alterations

Snail track degeneration

• Snail track degeneration forms sharply demarcated bands of white, wrinkled changes of the inner retinal surface, reminiscent of tracks made by a snail
• It has been called “cellophane-like” and may also occur in the macula. It is made up of cells that form a membrane anterior to the inner retinal surface
• Vitreoretinal adhesions may form at the margins of this degeneration which may have a rhegmatogenous potential
• Round holes without opercula may also develop
• Fibrillary changes of the vitreous body may occur with syneresis and optically empty liquefied pockets
• Snail track degeneration seems to occur more often in myopic eyes Don’t forget about the vitreous!