By volume, the vitreous is the largest component of the eye and yet it is often overlooked by both comprehensive ophthalmologists and retina specialists alike. In part, this is because it is difficult to see, both on clinical exam and on multimodal imaging. However, the latter is beginning to change, and in the process, much is being learned about this enigmatic structure.
Talia R. Kaden
The vitreous gel is a virtually acellular, highly hydrated (> 98% water) extracellular matrix. Its structure is maintained by a network of unbranched collagen fibrils comprised of collagen types II, V, IX, and XI. The glycosaminoglycan (GAG) hyaluronan is a major component that fills the spaces between these collagen fibrils.1 Although essential to the optical properties of the eye, the fact that it is an almost optically clear medium composed mainly of water makes it difficult to accurately describe its anatomical state.
Initially, the only source of information available was through in vivo biomicroscopic observations with an ophthalmoscope or a slit-lamp, providing a good but somewhat superficial insight as to its structure.2 Ex vivo histologic studies were unreliable due to numerous post-fixation artifacts caused by the high water content of the samples.2 This changed in 1976 when Jan Worst injected ink into the vitreous of postmortem eyes and identified a system of liquid spaces within the vitreous gel consisting of what he called the premacular bursa and cisterns surrounding the latter.3,4 Georg Eisner continued to expand our understanding when he used a modified slit-lamp camera to analyze postmortem eyes and not only confirmed Worst's findings,5 but also discovered areas of lower optical density in the vitreous cortex above the vessels, which he named “lücken,” (“gaps”), or prevascular fissures.6,7 In 1990, Kishi and Shimizu stained the vitreous with fluorescein in cadaveric eye specimens.8 They discovered that the premacular bursa was separated from the retina posteriorly by a thin layer of cortical tissue.8 They also defined the bursa as a boat-shaped, confined space that developed connections with other spaces only after a degenerative process of the vitreous.8 To emphasize this, they changed the term premacular bursa to posterior precortical vitreous pocket (PPVP). With the development of vitrectomy and use of intraocular stains, these structures were later visualized using triamcinolone intraoperatively.9
The Vitreous in the OCT Era
With the advent of optical coherence tomography (OCT), our understanding of in vivo ocular anatomy, and pertinently, vitreous anatomy, has expanded dramatically. Many have utilized the enhanced imaging capabilities of OCT to better understand the vitreous.10,11 In 2014, we developed an imaging protocol that allowed us to enlarge the size of the area scanned to 18 × 18 mm using swept-source OCT (SS-OCT).12 This approach made it possible to demonstrate that the premacular bursa is limited inferiorly, but contrary to what had been previously reported, continues superiorly beyond the reach of our instruments (Figures 1C and 1D).13 This scanning technique also provided visualization of the area of Martegiani separated from the bursa by the septum interpapillomaculare as described by Worst (Figure 1A).13 This separation disappears superiorly at a variable distance from the optic nerve, thereby creating a connection between these two spaces (Figure 1B).13 This differs from the small connection proposed by Kishi et al., who used SS-OCT to describe a connection between the PPVP and Cloquet's canal.10 It also differs from the supposed connection between the premacular bursa and the retrociliary circle of cisterns proposed by Worst.14 Instead, we pictured these spaces like a mitten, with the thumb part over the area of Martegiani, the finger and palm part over the macula, and the wrist and arm making their way towards the front of the eye, possibly terminating behind the lens in the space of Erggelet (Figure 1).14 The overall shape of the premacular bursa appears to be uniform early in life but may vary in size, as seen in a father and son with Stickler's disease.15 They presented with a “giant premacular bursa,” which may represent an optically empty vitreous in the setting of attached cortical vitreous.15
The top left image depicts schematically how the premacular bursa and prepapillary gap fuse at a variable distance from the optic nerve in the majority of adult eyes and is limited inferiorly but extends superiorly. These spaces can be readily seen on spectral-domain optical coherence tomography (OCT) and swept-source OCT. The horizontal B-scan below the optic nerve (A) shows how the area of Martegiani (the posterior portion of the prepapillary gap overlying the optic nerve head) is separated from the bursa (asterisk) by formed vitreous – the “septum interpapillomaculare” of Worst. The horizontal B-scan above the optic nerve (B) shows that the two spaces have fused, but a ridge persists as a legacy of the septum. The vertical B-scan in through the more central (C) and temporal macula (D) shows that the bursa (asterisk) is confined to the posterior pole inferiorly, but extends beyond the scan range superiorly. Adapted from: Engelbert M. A new understanding of vitreous structure. Review of Ophthalmology. 2016;01:60–64.
Our recent work also supported some of Eisner's work on prevascular fissures.16 In our study of normal volunteers, we detected thin hyporeflective spaces in the vitreous overlying first- and second-order blood vessels in young individuals without vitreous degeneration, corroborating the presence of the spaces Eisner had first described decades ago (Figure 2).6,7,16 With time, the vitreous is known to degenerate and these fissures appear to transform into bigger spaces, which likely correspond to the cisterns Worst described (Figure 3).16 Fissure planes in the more central vitreous appear also related to this degenerative process.13 A recently described aspect is the lamellar arrangement of fibers in the vitreous cortex.17 A novel model of fibrillar vitreous architecture characterized by a pattern of eyewall-parallel vitreous fibers with a tangential course toward the equator forms the vitreous cortex with some perpendicular fibers delimiting spaces deep inside the vitreous (premacular bursa, prepapillary gap, and prevascular fissures and cisterns).17 This lamellar pattern is compatible with the idea that with time and as degenerative changes ensue, the lamellae begin to separate, potentially resulting in vitreoschisis.
Swept-source optical coherence tomography (SS-OCT) images of three different subjects showing prevascular fissures (PVF) and their location above retinal blood vessels (black arrowheads). Infrared images in A, C, and E with arrows indicating scan position corresponding to vertical SS-OCT scans in B, D, and F. The black arrow points to a blood vessel with no PVF above it. Adapted from: Pang CE, Schaal KB, Engelbert M. Association of prevascular vitreous fissures and cisterns with vitreous degeneration as assessed by swept source optical coherence tomography. Retina. 2015;35:1875–1882.
Two subjects showing the relationship between premacular bursa (asterisks) and cisterns (white triangles). Infrared images in A and C with arrows indicating scan position corresponding to vertical swept-source optical coherence tomography scans in B and D. A and B show a teardrop configured cistern with no visible connection to the premacular bursa in the right eye of a 36-year-old man with an axial length (AL) of 24.1 mm. C and D show a bowl-configured cistern with visible connection to the premacular bursa in the left eye of a 51-year-old man with an AL of 24.2 mm. Adapted from: Pang CE, Schaal KB, Engelbert M. Association of prevascular vitreous fissures and cisterns with vitreous degeneration as assessed by swept source optical coherence tomography. Retina. 2015;35:1875–1882.
Clinical and Surgical Correlations
Knowledge of the normal vitreous anatomy and its characteristic aging changes is helpful in the clinical and surgical setting.18 For instance, it is well known that abnormal hyaloid adherence and tangential traction are implicated in the pathogenesis of vitreomacular traction (VMT) and macular hole (MH) formation. However, the status of the vitreous may also play an important role in those disorders.19 Although it might seem intuitive that eyes with advanced vitreous degeneration would have higher rates of macular holes or VMT, in fact, the opposite may be true.19 In a comparative study of eyes with VMT and MH versus control eyes, the former demonstrated significantly earlier stages of vitreous degeneration as compared to their matched controls, even when the latter were on average, younger. This may be because a degenerated vitreous creates a compartmentalization that buffers the inertia counterforces to the vitreoretinal interface (Figure 4), whereas a well-formed structure more effectively transmits any force applied to it.19 Going forward, this may allow for better prognostication for our patients regarding the likelihood of developing a vitreoretinal interface disease. It may also facilitate treatment, or one might postulate that a treatment that advances vitreous degeneration may concurrently reduce the risk of VMT or MH.
Eyes on the vitreomacular traction (VMT)-macular hole (MH) spectrum were found to be more likely to have a relatively intact vitreous gel (A), whereas eyes with an uneventful contralateral posterior vitreous detachment and no VMT in the study eye were significantly more likely to show more extensive vitreous degeneration with fissure planes(P = .048) (B, C). Diagrammatic horizontal section of an eye with formed vitreous, with saccadic forces being transmitted from more central formed vitreous onto the vitreoretinal interface without mitigation (D), whereas compartmentalization in an eye with more advanced vitreous degeneration and fissure planes buffers these forces (E). Adapted from: Ghadiali Q, Zahid S, Dolz-Marco R, Tan A, Engelbert M. An Assessment of Vitreous Degeneration in Eyes with Vitreomacular Traction and Macular Holes. J Ophthalmol. 2017;2017:6834692.
A better in vivo understanding of the vitreous can also be helpful in the postoperative course, as was true in this report in which SS-OCT was used to identify residual cortical vitreous in a patient with persistent floaters after surgery that were otherwise invisible on clinical examination (Figure 5).20
Widefield image (left) of a 28-year-old myope who complained of a crescentic opacity in his superotemporal peripheral field after undergoing vitrectomy for symptomatic vitreous opacities. Swept-source optical coherence tomography (1 and 2) demonstrated that a posterior vitreous detachment had been induced (red arrowhead), but that there was a residual posterior hyaloidal skirt with scalloped edges, presumably from cutter bites (green arrowhead). Further propagation of the vitreous separation and close shaving of the gel relieved this patient of his symptoms. Adapted from: Chen KC, Jung JJ, Engelbert M. Swept source optical coherence tomography of the posterior vitreous after pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):2041–2043.
The vitreous also plays an outsized role in the development of other intraocular diseases, including and especially in diabetes mellitus. Although known to impact the metabolic regulation throughout the body, in the vitreous, diabetic changes can lead to early liquefaction and cross-linking of the collagen network in a process known as diabetic vitreopathy.21,22 In a 2017 paper exploring the relationship between retinal neovascularization in patients with diabetic retinopathy and the posterior vitreous, nearly 80% of these membranes had grown along the outer surface of the posterior hyaloid face.23 Even the classic “wolf's jaw” configuration of neovascularization, which has been shown to track along the venous arcades, proliferates along the posterior hyaloid.23 However, in the setting of a largely attached vitreous cortex, the neovascularization can penetrate the posterior hyaloid and grow along the walls of prevascular fissures or cisterns, giving rise to flat, broad and tightly adherent plaques that can be challenging to tackle surgically. Given this information, a clear understanding of the relationship between diabetic neovascularization and the vitreous can not only aid in understanding this disease but also in surgical planning for these patients (Figure 6).23 Finally, the idea suggested by Kishi that the boat-shaped preretinal hemorrhages are confined to the premacular bursa and that their morphology is accounted by the shape of the latter24,25 was dismissed; OCT showed that the premacular bursal wall is permeable to erythrocyte passage, and an intrabursal bleed is followed by rapid infiltration of the adjacent vitreous gel by erythrocytes, giving rise to a hemorrhage with more indistinct margins (Figure 7).26
An appreciation of the complex relationship of diabetic neovascularization and the posterior hyaloid and the vitreous spaces is helpful in the surgical management of proliferative diabetics. The near infrared image (A) shows an active neovascular complex growing along a partially separated hyaloid. Schematic representation of a situation that can be approached readily with a cutter in B. C shows early neovascularization into a cistern in the setting of an attached posterior hyaloid. This is probably the precursor to flat, tightly adherent plaques that are not just tethered by a few pegs, and – if extensive – have to be delaminated bimanually. Adapted from: Vaz-Pereira S, Dansingani KK, Chen KC, Cooney MJ, Klancnik JM Jr, Engelbert M. Tomographic relationships between retinal neovascularization and the posterior vitreous in proliferative diabetic retinopathy. Retina. 2017;37(7):1287–1296.
Intrabursal hemorrhage due to Valsalva retinopathy. Ophthalmoscopy revealed a boat-shaped hemorrhage with indistinct margins adjacent to the inferior vascular arcade and a second hemorrhage inferior to the optic disk (A). There was no leakage identified on fluorescein angiography, but blockage over the vein the hemorrhage likely originated from B (red arrowhead). The vitreous was imaged using swept source optical coherence tomography, and the areas imaged with line scans are illustrated in the reflectance image (C). Note that erythrocytes are predominantly localized within the vitreous gel between the premacular bursa (stars) and the cortical vitreous. The bursal cavity itself is relatively devoid of erythrocytes; however, accumulation of erythrocytes within the vitreous adjacent to the bursa creates the impression that the bursal wall is lined with blood. Also note that the vitreous is attached at the macula, and the subhyaloid space is optically clear without any evidence of hemorrhage. Adapted from: Balaratnasingam C, Vaz-Pereira S, Engelbert M. Intrabursal and Subhyaloid Hemorrhages in Valsalva Retinopathy. Retina. 2017;37(1):e1–e3.
The vitreous is a complex structure that involved in diverse pathologic processes. As our multi-modal imaging capabilities have expanded, so too has our understanding of in vivo anatomy and with that, the opportunity to better understand vitreoretinal pathology. Further research will continue to grow this knowledge base and provide an even more complete understanding of the vitreous and its impact.
- Bishop PN. Structural macromolecules and supramolecular organisation of the vitreous gel. Prog Retin Eye Res. 2000;19(3):323–344. doi:10.1016/S1350-9462(99)00016-6 [CrossRef] PMID:10749380
- Fine BS, Tousimis AJ. The structure of the vitreous body and the suspensory ligaments of the lens. Arch Ophthalmol. 1961;65(1):95–110. doi:10.1001/archopht.1961.01840020097017 [CrossRef] PMID:13699560
- Worst JGF. The bursa intravitrealis premacularis: New developments in ophthalmology. In: Deutman AF, ed. New Developments in Ophthalmology Nijmegen 16–18 October 1975. Springer, Dordrecht; 1976:275–279. doi:10.1007/978-94-010-1569-1_31 [CrossRef]
- Jongebloed WL, Worst JFG. The cisternal anatomy of the vitreous body. Doc Ophthalmol. 1987;67(1–2):183–196. doi:10.1007/BF00142712 [CrossRef] PMID:3428097
- Eisner G. Clinical anatomy of the vitreous. In: Duane TD, Jaeger EA, eds. Biomedical Foundations of Ophthalmology. Vol 1. Philadelphia: J.B. Lippincott Co; 1990:chap 16.
- Eisner G. Biomicroscopy of the peripheral fundus. New York, NY: Springer-Verlag; 1979.
- Eisner G. Clinical anatomy of the vitreous. In: Jacobiec F, ed. Ocular Anatomy, Embryology, and Teratology. Philadelphia, PA: Harpe & Row Publishers; 1982:391–424.
- Kishi S, Shimizu K. Posterior precortical vitreous pocket. Arch Ophthalmol. 1990;108(7):979–982. doi:10.1001/archopht.1990.01070090081044 [CrossRef] PMID:2369358
- Fine HF, Spaide RF. Visualization of the posterior precortical vitreous pocket in vivo with triamcinolone. Arch Ophthalmol. 2006;124(11):1663. doi:10.1001/archopht.124.11.1663 [CrossRef] PMID:17102022
- Itakura H, Kishi S, Li D, Akiyama H. Observation of posterior precortical vitreous pocket using swept-source optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54(5):3102–3107. doi:10.1167/iovs.13-11769 [CrossRef] PMID:23599325
- Spaide RF. Visualization of the posterior vitreous with dynamic focusing and windowed averaging swept source optical coherence tomography. Am J Ophthalmol. 2014;158(6):1267–1274. doi:10.1016/j.ajo.2014.08.035 [CrossRef] PMID:25174895
- Pang CE, Freund KB, Engelbert M. Enhanced vitreous imaging technique with spectral-domain optical coherence tomography for evaluation of posterior vitreous detachment. JAMA Ophthalmol. 2014;132(9):1148–1150. doi:10.1001/jamaophthalmol.2014.1037 [CrossRef] PMID:25010436
- Schaal KB, Pang CE, Pozzoni MC, Engelbert M. The premacular bursa's shape revealed in vivo by swept-source optical coherence tomography. Ophthalmology. 2014;121(5):1020–1028. doi:10.1016/j.ophtha.2013.11.030 [CrossRef] PMID:24507856
- Engelbert M. A new understanding of vitreous structure. Rev Ophthalmol. 2016;01:60–64.
- Chen KC, Jung JJ, Engelbert M. Giant premacular bursa: a novel finding of the posterior vitreous in two patients with Stickler syndrome type 1 revealed by swept-source optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2016;254(3):591–593. doi:10.1007/s00417-015-3125-9 [CrossRef] PMID:26245341
- Pang CE, Schaal KB, Engelbert M. Association of prevascular vitreous fissures and cisterns with vitreous degeneration as assessed by swept source optical coherence tomography. Retina. 2015;35(9):1875–1882. doi:10.1097/IAE.0000000000000540 [CrossRef] PMID:25874366
- Gal-Or O, Ghadiali Q, Dolz-Marco R, Engelbert M. In vivo imaging of the fibrillar architecture of the posterior vitreous and its relationship to the premacular bursa, Cloquet's canal, prevascular vitreous fissures, and cisterns. Graefes Arch Clin Exp Ophthalmol. 2019;257(4):709–714. doi:10.1007/s00417-018-04221-x [CrossRef] PMID:30617583
- Kishi S. Diagnostic pearls in the management of vitreomacular disorders. Semin Ophthalmol. 1998;13(1):2–9. doi:10.3109/08820539809066077 [CrossRef] PMID:9567007
- Ghadiali Q, Zahid S, Dolz-Marco R, Tan A, Engelbert M. An Assessment of Vitreous Degeneration in Eyes with Vitreomacular Traction and Macular Holes. J Ophthalmol. 2017;2017:6834692. doi:10.1155/2017/6834692 [CrossRef] PMID:28133544
- Chen KC, Jung JJ, Engelbert M. Swept source optical coherence tomography of the posterior vitreous after pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):2041–2043. doi:10.1007/s00417-015-3018-y [CrossRef] PMID:25904299
- Sebag J. Diabetic vitreopathy. Ophthalmology. 1996;103(2):205–206. doi:10.1016/S0161-6420(96)30716-1 [CrossRef] PMID:8594502
- Stitt AW, Moore JE, Sharkey JA, et al. Advanced glycation end products in vitreous: structural and functional implications for diabetic vitreopathy. Invest Ophthalmol Vis Sci. 1998;39(13):2517–2523. PMID:9856760
- Vaz-Pereira S, Dansingani KK, Chen KC, Cooney MJ, Klancnik JM Jr, Engelbert M. Tomographic relationships between retinal neovascularization and the posterior vitreous in proliferative diabetic retinopathy. Retina. 2017;37(7):1287–1296. doi:10.1097/IAE.0000000000001336 [CrossRef] PMID:27749694
- Kishi S, Shimizu K. Clinical manifestations of posterior precortical vitreous pocket in proliferative diabetic retinopathy. Ophthalmology. 1993;100(2):225–229. doi:10.1016/S0161-6420(93)31666-0 [CrossRef] PMID:8437831
- Kishi S. Vitreous anatomy and the vitreomacular correlation. Jpn J Ophthalmol. 2016;60(4):239–273. doi:10.1007/s10384-016-0447-z [CrossRef] PMID:27165709
- Balaratnasingam C, Vaz-Pereira S, Engelbert M. Intrabursal and Subhyaloid Hemorrhages in Valsalva Retinopathy. Retina. 2017;37(1):e1–e3. doi:10.1097/IAE.0000000000001149 [CrossRef] PMID:28005722