The vitreous is the largest structure within the eye, occupying approximately 80% of the total occur volume.1 It is composed of 98-99% water, held together in a gel-like structure by a 3D network of type II collagen fibrils, separated by hyaluronan (HA) and other macromolecules.2, 3 The collagen network provides mechanical strength, allowing the vitreous to sustain impacts, and transmit tractional forces to the retinal surface.2 The vitreous functions as a pathway for nutrients which are utilized by the lens, ciliary body and retina, as well as providing structural support for the globe.4 Vitreoretinal attachments are formed between the posterior hyaloid membrane and the internal limiting membrane of the retina at the vitreous base near the ora serrata, the optic disc, the fovea and along major retinal blood vessels.3, 5 The vitreous also has attachments to the posterior lens surface.
Anatomy
Due to its intrinsically transparent nature, the vitreous structure has previously proved incredibly difficult to investigate. Previously, knowledge of the vitreous structure was developed during vitreoretinal surgery aided by triamcinolone staining 6 and postmortem studies.7
Recently, use of long wavelength scanning in Swept Source optical coherence tomography (SS-OCT) has revealed structures in the vitreous that were previously unseen with shorter wavelength time domain – and spectral domain (SD) – OCT. Coupled with greater imaging depths of approximately 2.6mm with SS-OCT versus approximately 1.9mm with SD-OCT, far greater areas of vitreous can be imaged.8 In-vivo studies with SS-OCT have revealed several channels of liquid spaces within the vitreous (Figure 1).
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The first of these channels that overlies the macular region is known as the premacular bursa and has been described as a ‘boat shaped lacunae in the macular area’, present in both young and old eyes.9
The second channel, positioned around the optic nerve is known as the area of Martegiani which connects to the premacular bursa in the majority of eyes, and extends anteriorly into the hyaloidal tract (Cloquet’s canal) towards the crystalline lens.8 These lacunae have been found to have a low density of collagen fibrils and a relatively high concentration of hyaluronan molecules.10 These observations of the vitreous may have important implications in understanding the pathogenesis of a variety of pathological ocular conditions. For example, knowledge of the communication between Cloquet’s canal and the premacular bursa may explain how inflammatory mediators released anteriorly following cataract surgery diffuse posteriorly to the macula, resulting in macular oedema.11
The uncomplicated posterior vitreous detachment
The vitreous undergoes progressive structural changes and liquefaction with age.4 Evidence of liquefaction (vitreous synchysis) has been seen in patients as young as four years of age, with approximately 20% of the vitreous being liquid by the age of 20, and 50% by the age of 80-90 years.12, 13 Liquefaction, which leads to the formation of large pockets of liquid vitreous – recognized clinically as lacunae 14 – is known to occur at a faster rate in myopic eyes.15 Vitreous synchysis is accompanied by aggregation (syneresis) of the collagen fibrils as a consequence of the changes in the chemical and conformational state of hyaluronan and its interaction with collagen.3
Posterior vitreous detachment (PVD) can be defined as a separation between the posterior vitreous cortex and the internal limiting lamina of the retina and can be either localised, partial or total, depending on the extent of detachment (Figure 2). PVD typically arises due to interplay between vitreous synchysis and the weakening of the adhesions between the posterior hyaloid membrane and the retina.
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Once liquefied, the vitreous can find its way to the retrocortical space through a prepapillary hole in the posterior hyaloid membrane.16 Early in the PVD process, the vitreous detaches from the perifoveal area, but maintains attachment at the central fovea and the optic disc, where vitreoretinal attachments are stronger.17, 18 Over time, and helped by ocular movement, the vitreous fluid gradually dissects a plane between the vitreous cortex and the internal limiting membrane, eventually leading to a complete PVD and collapse of the remaining vitreous gel.19
OCT studies of the process of PVD have shown that total detachment is a particularly slow process, often taking decades for completion.20
Incidence of PVD is seen to increase with age. Reports of PVD in emmetropic subjects are rare under 40 years of age, with the incidence increasing with age to 50% at 50 years, 65% beyond 65 years and up to 87% beyond 90 years.21, 22 Risk factors associated with earlier onset of PVD include myopia, ocular trauma, ocular surgery, aphakia, intraocular inflammation, diabetes and postmenopausal women.23-25
Floaters and photopsia are the most commonly reported symptoms with the sudden onset of a PVD. 26 While floaters are caused by aggregations in the collagen fibrils within the vitreous, photopsia are assumed to be a consequence of direct retinal stimulation during vitreous traction.3, 27
Floaters secondary to vitreous aggregations can be distinguished from pigment released secondary to a retinal tear due to the lower number and larger size. Classically, photopsia caused by PVD is described as brief, monocular lightning streaks, typically vertically oriented and occurring temporally.28
Anomalous posterior vitreous detachment
Anomalous PVD occurs when the extent of vitreous syneresis exceeds the degree of weakening between the posterior hyaloid membrane and the internal limiting membrane of the retina, resulting in traction across the vitreoretinal interface.29 The most common location of persistent traction is at the macular, leading to vitreomacular traction (VMT) (Figure 3).26
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Clinical presentation of VMT is highly variable, with symptoms ranging from mild blurring and distortion to severe decrease in VA (< 6/18) with severe distortion,30 depending on the extent of accompanying macular pucker and macular oedema.13 However, symptoms are usually mild with slow reduction of vision due to chronic traction. Progression of VMT over time results in either spontaneous PVD with anatomic and visual improvement, or progression to partial or full thickness macular hole. Self-monitoring with an Amsler grid and review with OCT is advised if the patient is relatively asymptomatic and VMT is a chance finding. 31 However, referral is warranted if VA is significantly affected and OCT appearance points towards possible impending macular hole formation.
Previously, the only treatment option for patients with symptomatic VMT was a highly invasive vitrectomy. However, advances in pharmaceuticals have led to the development of ocriplasmin (Jetrea), an intravitreal injection containing protease enzyme, which breaks down the vitreoretinal attachments, inducing PVD.32 Although NICE approved since 2013, strict criteria restrict the use of ocriplasmin to patients who have no epiretinal membrane (ERM), a stage II full-thickness macular hole (diameter less than 400 microns) and/or severe visual symptoms.33 In addition, due to the high cost of the drug (£2,500 per injection), use varies across the country, depending on approval in different health boards. Ocriplasmin has been found to induce PVD in up to 37.4% of patients with VMT alone, and up to 50% of patients with VMT and macular hole.31
If ocriplasmin is not suitable or available, vitrectomy is the other mode of treatment for VMT. This can be combined with a membrane peel if an ERM is present. Due to the invasiveness of the procedure, vitrectomy is usually only carried out in patients who have severe visual symptoms, where an improvement in vision should be possible. Reports on surgical outcomes suggest improvement in VA occurs in up to 78% of cases,34 with better surgical outcomes in patients with a shorter duration of symptoms, lower preoperative macular thickness and with smaller focal attachments.35
Macular hole
If VMT persists during PVD it can lead to the formation of a macular hole. Macular holes are typically seen in females in the sixth or seventh decade of life, with a prevalence of 1/3300. 37 Macular holes can be classified using OCT into four stages as follows:
• Stage 1: Vitreomacular traction, with flattening of the foveal dip and a small reduction in VA.
• Stage 2: Small full thickness macular hole of less than 250µm diameter with persistent vitreomacular adhesion.
• Stage 3: Medium-sized full thickness macular hole between 250-400µm in diameter with persistent vitreomacular adhesion (Figure 4A).
• Stage 4: Large full thickness macular hole over 400µm in diameter without vitreomacular adhesion (Figure 4B).
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Occasionally during macular hole development the vitreous spontaneously detaches from the retina before a full thickness macular hole has developed. This can leave the retina with an unusual foveal contour and a partial thickness hole, which is referred to as a lamellar hole (Figure 5). Lamellar holes are considered the end result of an abortive process in full thickness macular hole formation. However, they have also been seen to occur in the absence of PVD, with aetiology hypothesised to be secondary to either contraction of an epiretinal membrane (ERM).38
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Classification of lamellar hole can be based upon four qualitative criteria: (1) an irregular foveal contour; (2) a break in the inner fovea; (3) a dehiscence of the inner foveal retina from the outer retina; and (4) an absence of a full thickness foveal defect with intact foveal photoreceptors.38 Dehiscence, or splitting, of the inner and outer retinal layers is a common feature of lamellar holes, with the separation most often occurring at the level of the outer plexiform layer, with strands of retinal tissue spanning the separation.38, 39 As lamellar holes do not extend down to the photoreceptive layers, VA is usually unaffected. Lamellar macular hole is regarded as a stable macular condition; therefore, close monitoring is not necessary and no treatment is indicated.40 41 Treatment of lamellar hole with vitrectomy has been seen to lead to full thickness macular hole formation in some cases.38 Lamellar holes should not be confused with macular pseudoholes, which can be defined as macular lesions that have the appearance of macular holes on fundoscopy, but which do not have any loss of foveal tissue and have a steepened foveal contour secondary to ERM contraction.
Without OCT examination macular holes – particularly partial thickness ones – can be difficult to spot. The Watzke-Allen test, performed by projecting a narrow slit beam vertically and horizontally across the centre of the macula, can be useful in determining the presence of a hole. Patients with a macular hole will report that the beam is thinned or broken, whilst those without a hole will usually see a distorted beam of uniform thickness.42
Depending on the stage of macular hole, management is with either ocriplasmin or vitrectomy. Up to 10% of cases of stages 1-3 macular holes spontaneously close, therefore the majority will require treatment.43 Whilst vision remains at a reasonable level, ophthalmologists will often observe traction for a period of at least 3 months, to see if spontaneous resolution occurs. However, as post surgical outcomes are better in patients with a shorter duration of symptoms, ophthalmologists must be careful not to put off surgery for too long.35 In one study, in patients with a macular hole of less than 6 months duration, successful closure was achieved in 95% of patients, compared with 47% in patients with a macular hole greater than a year.44 Given the clinical outcomes post surgery, recent onset macular hole does not represent an ocular emergency.
Epiretinal membrane
PVD is believed to have a critical role in the pathogenesis of idiopathic ERM. The prevalence of ERM in large scale studies has been reported to be between 2.2-26.1%.45 Large scale clinical studies have shown that 80-95% of eyes with idiopathic ERM have either a partial or complete PVD.46 Other causes for the development of ERM comprise: retinal surgery including photocoagulation and cryotherapy, retinal vascular disease, intraocular inflammation and ocular trauma.
The process by which PVD stimulates ERM formation is believed to be caused by one of two mechanisms.13 First, tractional forces during PVD result in breaks in the retina’s inner limiting membrane, allowing migration of glial cells (non-neuronal retinal cells that provide neuronal support) to the inner retinal surface where they proliferate. Alternatively, ERMs may result from the transdifferentiation (cell conversion) and proliferation of hyalocytes of vitreous origin that are left behind on the retinal surface following PVD. 47 Vitrectomy specimens have shown that ERMs comprise RPE cells, macrophages, fibrocytes and collagen cells as well as glial cells.
The clinical appearance of ERM can vary dramatically depending on their thickness and associated distortion of retinal vasculature. Gass proposed grading the severity of ERM’s on the following clinical scale: grade 0, translucent membranes unassociated with retinal distortion; grade 1, membranes causing irregular wrinkling of the inner retina; and grade 2, opaque membranes casing obscuration of the underlying vessels and marked full-thickness retinal distortion.48 When the membrane is thin and translucent, it is often referred to as ‘cellophane maculopathy’ (grade 1). In these cases the membrane is seen on fundoscopy as an irregular light reflex or sheen over the macula. As the membrane thickens and contracts it creates retinal folds and is known as ‘macular pucker’ (grade 3). On OCT examination, ERM appear as a thin, hyper-reflective band which extend across the surface of the retina (Figure 6). The majority (70%) of ERM are globally adherent to the retina, whilst the rest have only focal adhesions. 49, 50
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Unlike in cellophane maculopathy when vision can remain relatively unaffected, macular pucker typically causes reduction in vision to 6/12 or worse, with associated metamorphopsia and micropsia and occasional monocular diplopia.45 In severe cases, ERM is associated with retinal thickening and oedema, which is often diffuse in pattern. This is believed to be caused by mechanical stress resulting in retinal Müller cells releasing inflammatory factors causing localized inflammation and breakdown of the blood retinal barrier. 51
Management of patients with ERM in practice should ideally involve monitoring with OCT and careful assessment of patient symptoms, along with advice on self-monitoring. Referral for ophthalmological assessment should only be made if the patient has significant visual symptoms (typically VA < 6/18) or if it is affecting their daily life. Currently, the only way to treat patients with ERM is with vitrectomy and membrane peeling, with visual improvement reported to be achieved in 66-90% of cases.52 However, recurrence of ERM following surgery is high, occurring in 10-21% of cases.
Summary
Thanks to rapidly advancing imaging technologies, our knowledge of the vitreous in health and disease continues to expand. Whilst the majority of patients will likely experience little more vitreous related problems than the occasional floater, optometrists must be aware of the complications associated with posterior vitreous detachment including VMT, macular hole and ERM. Correct management and appropriate timely referral of these conditions is important in ensuring optimum recovery of visual acuity.
Dr Rachel Hiscox is education and clinical affairs manager, UK & Ireland for Topcon (GB) Ltd and an optometrist with experience in hospital and private practice
Special thanks
A special thanks to Nicholas Rumney and Tim Cole for providing the images used in this article.
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