玻璃体浑浊的分子原理

【1】中提到玻璃体中IX型覆盖在II型胶原蛋白的外面，IX型上面有硫酸软骨素链。

随着年龄增加，硫酸软骨素和IX型胶原蛋白的丢失，导致具有粘性的II型胶原蛋白暴露在外面，聚集导致形成玻璃体混浊

【2】的文章结尾提到，硫酸软骨素可以清除自由基，换言之，自由基具有氧化和攻击硫酸软骨素的的能力。

Biochemical analysis reveal that vitreous consists of a fibrillar component, comprised of collagen and glycosaminoglycans (GAGs), chiefly hyaluronan (HA) with much lower concentrations of chondroitin sulfate (CS) and heparan sulfate (HS). The core of each fibril is composed of type V/XI collagen, which is surrounded by a sheath of fibrillar type II collagen as well as a regular arrangement of type IX collagen along the outermost surface of the fibril, HA provides a swelling pressure to the collagen network and hence the vitreous gel [5–6]. Recent research has shown that the loss of CS chains from type IX collagen of the fibril surfaces together with an increased surface exposure of type II collagen can result in collagen fibrillar aggregation. Gradual and progressive aggregation of the collagen fibrils results in a redistribution of the collagen fibrils, leaving areas devoid of collagen fibrils and thereby converted into a liquid. This pathological process can progress to posterior vitreous detachment (PVD), causing blindness [7–9]. Clarifying the chemical structure of CS and other GAGs within the vitreous can improve our understanding the interaction between GAGs and collagen, important for stabilizing the vitreous fibrillar network.

（生化分析显示，玻璃体由一种纤维组成，由胶原和糖胺聚糖（GAG）组成，主要是透明质酸（HA），其中硫酸软骨素（CS）和硫酸乙酰肝素（HS）的浓度要低得多。每个原纤维的核心由V/XI型胶原组成，该胶原被II型胶原纤维鞘以及沿原纤维最外表面的IX型胶原的规则排列所包围，HA向胶原网络以及玻璃体凝胶提供膨胀压力[5–6]。最近的研究表明，纤维表面IX型胶原中CS（硫酸软骨素）链的丢失以及II型胶原表面暴露的增加可导致胶原纤维聚集。胶原纤维的逐渐聚集导致胶原纤维的重新分布，留下没有胶原纤维的区域，从而转化为液体-表现为液化。这种病理过程可发展为后玻璃体脱离（PVD），导致失明[7-9]。阐明玻璃体内CS和其他GAG的化学结构可以提高我们对GAG和胶原之间相互作用的理解，这对稳定玻璃纤维网络很重要。）【3】

这段话的意思是，从内到外：

V/XI型胶原蛋白->II型胶原蛋白->IX胶原蛋白->硫酸软骨素

Bovine vitreous CS consisted of 2S4S, 2S6S, 4S, 6S and 0S with 4S (48.8%), 0S (37.6%) and 6S (11.9%) as the main compositional disaccharides and 2S6S (1.5%) and 2S4S (0.3%) as minor ones（牛玻璃体CS由2S4S、2S6S、4S、6S和0S组成，其中4S（48.8%）、0S（37.6%）和6S（11.9%）为主要成分双糖，2S6S（1.5%）和2S4S（0.3%）为次要成分。）【3】

Type IX collagen and versican are reportedly the major CS containing proteoglycans in the vitreous. Structural characterization of CS has relied on the isolation of vitreous proteoglycans and the subsequent analysis of the disaccharide compositions of their GAG chains. In this way, the CS GAG chains of type IX collagen in bovine vitreous was determined to be 15-60 kDa consisting predominantly of 4-sulfated (50%) and 6-sulfated (30%) with lesser amounts of unsulfated (18%) diasaccharides residues [10–11]（据报道，IX型胶原和versican是玻璃体中含有蛋白多糖的主要CS。CS的结构表征依赖于玻璃体蛋白多糖的分离及其GAG链双糖成分的后续分析。通过这种方式，牛玻璃体中IX型胶原的CS-GAG链被确定为15-60 kDa，主要由4-硫酸酯（50%）和6-硫酸酯（30%）组成，其中含有少量未硫酸酯（18%）一糖残基[10–11]）【3】

【4】 Filling the space between the collagen fibrils is a network of hyaluronan; this glycosaminoglycan (polysaccharide) attracts water and generates a swelling pressure that inflates the gel.（胶原纤维之间充满了透明质酸网络；这种糖胺聚糖（多糖）吸水并产生膨胀压力，使凝胶膨胀。）

Vitreous structure
The vitreous is a highly hydrated gel-like structure (>98% water) that is normally acellular, apart from a few cells called hyalocytes in the vitreous cortex.7 The gel state of the vitreous is maintained by a network of long, thin collagen fibrils that are ~15 nm in diameter. The concentration of these collagen fibrils is highest in the vitreous base and decreases posteriorly, but then increases in the cortical layer of the vitreous, which is attached to the inner surface of the retina. Filling the space between the collagen fibrils is a network of hyaluronan; this glycosaminoglycan (polysaccharide) attracts water and generates a swelling pressure that inflates the gel.(玻璃体是一种高度水合的凝胶状结构（>98%水），通常是无细胞的，除了玻璃体皮质中的一些称为透明细胞的细胞外。7玻璃体的凝胶状态是由一个长而薄的胶原纤维网络维持的，其长度约为15 纳米直径。这些胶原纤维的浓度在玻璃体基底部最高，并在后部降低，但随后在附着于视网膜内表面的玻璃体皮质层增加。胶原纤维之间充满了透明质酸网络；这种糖胺聚糖（多糖）吸水并产生膨胀压力，使凝胶膨胀。)【4】

The collagen fibrils are composed of collagen types II, V/XI and IX. Collagen types II and V/XI form the core of the rope-like collagen fibrils, whereas type IX collagen molecules are regularly distributed along the fibril surfaces.7 The type IX collagen has chondroitin sulfate glycosaminoglycan chains attached to it which extend away from the fibril surfaces and space apart the collagen fibrils, thereby preventing fibril aggregation (Figure 1).8 The individual collagen fibrils are organised into small bundles, and interconnections between these bundles allow the formation of an extended network that maintains the gel state（胶原原纤维由II型、V/XI型和IX型胶原组成。II型和V/XI型胶原形成绳状胶原原纤维的核心，而IX型胶原分子沿着原纤维表面规则分布。7.IX型胶原上附着有硫酸软骨素-糖胺聚糖链，该链远离原纤维表面，并与胶原原纤维隔开，从而防止原纤维聚集（图1）。8单个胶原原纤维被组织成小束，这些束之间的相互连接允许形成一个维持凝胶状态的扩展网络。）【4】

a是正常玻璃体里面的胶原纤维

b是玻璃体混浊

Natural history
Many patients experience floaters, but generally the symptoms are not troublesome. The vitreous opacities are mobile and move out of the visual axis, especially after a PVD when they move anteriorly causing the symptoms to diminish.5 Serpetopoulas et al16 have mathematically shown that the shadow of a vitreous opacity on the retina is determined by the diameter of the opacity, its distance from the retina and the overall distance between the pupillary plane and the retina. As these vitreous opacities move forward, over time their conic shadow no longer reaches the retina and the patient does not perceive them or only sees them intermittently.

（自然史

许多患者都会出现漂浮物，但通常情况下症状并不麻烦。玻璃体混浊是可移动的，并移出视轴，尤其是在PVD后，当它们向前移动时，症状减轻。5 Serpetopoulas等人从数学上证明，视网膜上玻璃体混浊的阴影由混浊的直径、其与视网膜的距离以及瞳孔平面与视网膜之间的总距离决定。随着这些玻璃体混浊向前移动，随着时间的推移，它们的锥形阴影不再到达视网膜，患者无法察觉或只是间歇性地看到它们。）

Alternatively Schulz-Key et al5 have suggested that because vitreoretinal surgeons are inherently reluctant to operate on patients with SVO who have excellent visual acuity（医生不愿意为视力良好但是有飞蚊的患者进行手术）

symptomatic vitreous opacities (SVO)（症状性玻璃体混浊）

All these studies have suggested certain potential personality traits in patients with SVO, but at present there is no definitive evidence regarding the psychology of this cohort of patients.（所有这些研究都表明SVO患者具有某些潜在的人格特征，但目前还没有关于这组患者心理的确切证据。）

All patients in this cohort were either pseudophakic or aphakic to avoid the progression of lenticular cataract seen in phakic patients following vitrectomy（玻切只针对假晶状体或无晶状体人群）

One patient developed a post-vitrectomy RD that was successfully repaired subsequently, and one patient had progression of lenticular sclerosis. （一名患者玻切时发生视网膜后脱离，随后修复）

Floaters-only-vitrectomy.
Recently Sebag et al39 have published a prospective study on PPV for floaters. They performed 25-gauge PPV for symptomatic floaters of at least 24 months’ duration in 76 eyes, and evaluated the efficacy in 16 patients using contrast sensitivity function and subjective visual function using NEI VFQ. In this study the authors performed Floaters-only-Vitrectomy (FOV), which is defined as vitrectomy without PVD induction if PVD is not present at the start of surgery to theoretically reduce the risk of iatrogenic retinal breaks. In addition, anterior vitreous was left in situ to protect the lens against free oxygen radicals and reduce post-PPV cataract formation. It was concluded that PPV for floaters is highly efficacious, with contrast sensitivity that was diminished by 67% in patients with floaters normalising in all cases up to 9 months post-surgery, and the visual function improving by 29.2%. This technique was found to be highly safe with no case of post-PPV retinal breaks or RD, and only 23.5% developing cataract at an average of 15 months post-operatively. The mean age of this subgroup was 60.5 years (range 53–66 years). The main risk with FOV is that not only does the absence of PVD induction intra-operatively leave the risk of vitreous detaching later and leading to post-PPV retinal breaks and RD, but also causing the recurrence of symptomatic floaters. The authors have acknowledged themselves that 1 out of 76 eyes in their cohort developed symptomatic floaters during the onset of PVD later requiring a repeat vitrectomy.（尽量减少玻璃体切除，以避免切除后氧化晶状体）

The most serious risk of intraocular surgery is endophthalmitis, and in the context of vitrectomy for floaters, this is of utmost importance as patients invariably have excellent visual acuity before surgery. Recently there have been two reports of endophthalmitis following PPV for SVO. Henry et al41 presented a case of Staphylococcus caprae endophthalmitis following 20-G vitrectomy for vitreous floaters, which was treated with vitreous tap and intravitreal antibiotics. The patient had a pre-PPV visual acuity of 6/9, which worsened after the endophthalmitis to 6/24 at 9 months partially limited by the nuclear sclerotic cataract. Similarly, Park et al42 have published a large, prospective nation-wide study looking at endophthalmitis after PPV in UK. In their series, 28 out of a total of 48 433 eyes (1 in 1730) undergoing vitrectomy developed endophthalmitis. Two of the patients developed this complication after surgery for SVO, with one patient regaining a visual acuity of 6/9 at 6 months, whilst the other developed CMO and ended up with a visual acuity of 6/96.（玻切可能导致眼内炎）

68% of patients had floaters for >6 months with most marked symptoms generally on reading（68%的人在阅读时漂浮物很明显）

Mason et al,23 73% of patients described their daily severity of symptoms as ‘severe’ or ‘very severe’, 50% had problems with reading, 30% with driving, 12% with occupational tasks, and 8% with leisure activities.（73%的患者将其日常症状严重程度描述为“严重”或“非常严重”，50%的患者有阅读问题，30%的患者有驾驶问题，12%的患者有职业任务，8%的患者有休闲活动问题。）

In series where full vitrectomy was carried out for floaters, Tan et al6 reported the incidence of cataract at 50% over a mean follow-up of 10.1 months. This is comparable to the incidence of 60% given by Schulz-Key et al5 over a mean follow-up period of 37 months. In the study by de Nie et al,21 of 50 eyes with clear lens before surgery, 19 eyes (38%) underwent cataract surgery during a period of 26.4 months. FOV with sparing of anterior vitreous is theoretically more lens friendly and the reported rate of cataract formation is lower at 23.5% (over 15 months) and 22.5% (over 18 months) in the two large studies by Sebag et al39 and Mason et al.23（定点玻切一两年内23%会出现浑浊）

The subsequent work by Delaney et al30 was even less encouraging; the authors concluded that intravitreal Nd-YAG vitreolysis relieved symptoms in only a third of patients and the clinical improvement was only moderate in degree, subjectively being graded at no greater than 50% by 93.3% of patients.30 Moreover, in no patient was there a complete resolution of symptoms. Also laser treatment led to worsening of symptoms in 7.7% of their patients.（玻璃体腔内Nd-YAG玻璃体溶解术仅能缓解三分之一患者的症状，临床改善程度仅为中度，93.3%的患者主观评分不超过50%。30此外，没有一名患者的症状完全消失。激光治疗也导致7.7%的患者症状恶化。）

There has been a recent report of a risk of refractory open-angle glaucoma following Nd-YAG vitreolysis of vitreous floaters.52 Cowan et al52 have reported on 3 eyes of 2 patients who presented with an intraocular pressure of >40 mm Hg at varying intervals (1 week to 8 months) after this procedure. Initially all eyes were managed medically with two of them requiring selective laser trabeculoplasty and two needing glaucoma-drainage surgery with trabectome before intraocular pressure stabilised. This risk was not linked to inflammation or steroid use. The authors hypothesised that vitreous micro-debris or macrophages laden with vitreous material may have migrated anteriorly and blocked the trabecular meshwork. Intraocular pressure rise following laser vitreolysis has also been reported by Little et al,51 but it has mostly been for eyes with vitreous strands to cataract wounds and the spike of pressure has been temporary. A protracted and chronic rise in intraocular pressure presumed to be owing to decrease in outflow facility of the trabecular meshwork has not been reported by the few other studies on this subject, and this risk may need further investigation.（激光后的碎片会堵塞小梁网导致眼压上升、开角型青光眼）

Phacoemulsification combined with deep anterior vitrectomy.
Finally phacoemulsification combined with deep anterior vitrectomy through a posterior curvilinear capsulorhexis has also been described for symptomatic floaters.4 However, there is only one paper of 10 eyes describing this technique, the major limitation being that this technique is limited to elderly individuals with advancing lens opacities and can only treat floaters in the anterior vitreous. Also cystoid macular oedema was seen post-operatively in 2 of the 10 eyes described in this paper.（声乳化联合深前段玻璃体切除术。

最后，对于有症状的漂浮物，超声乳化联合经后囊环形撕囊的深部前部玻璃体切除术也有报道。4然而，只有一篇10只眼的论文描述了这项技术，主要的局限性在于，这项技术仅限于患有晶状体混浊的老年人，并且只能治疗玻璃体前部的漂浮物。本文描述的10只眼中有2只眼术后出现黄斑囊样水肿。）

Eventually the patient should make an informed decision based on whether living with the functional consequences of a non-blinding condition outweighs the option of a highly efficacious but not risk-free procedure.（最终，患者应该根据生活在非致盲状态下的功能性后果是否比选择高效但非无风险的手术更重要，做出明智的决定。）

上面内容来自【4】

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Type VI collagen
Type VI collagen is a ubiquitous component of extracellular matrices and has been identified in small quantities in human and bovine vitreous.29 It is not a component of the heterotypic collagen fibrils but instead forms separate microfibrils. Type VI collagen has been shown to bind fibrillar collagens and HA,30 so it could have a role in linking together the heterotypic collagen fibrils and HA in vitreous.

（VI型胶原

VI型胶原是细胞外基质中普遍存在的成分，在人和牛的玻璃体中已被少量鉴定。29它不是异型胶原纤维的组成部分，而是形成单独的微纤维。VI型胶原已被证明能结合原纤维胶原和透明质酸30，因此它可能在连接玻璃体中异型胶原原纤维和透明质酸方面发挥作用。）

Hyaluronan
HA is the predominant GAG in mammalian vitreous and was first isolated from bovine vitreous humour more than 70 years ago.38 It is a linear, polymeric GAG built from repeating disaccharide units (β1–4 glucuronic acid β1–3 N-acetylglucosamine)n. Chains of HA can be very long and form networks through entanglement. It is distinguished from the other GAGs in that it is not synthesised covalently, linked to a core protein, and it is never sulphated. HA is not uniformly distributed within the vitreous and is found in the highest concentration in the posterior vitreous cortex.10 In adult human vitreous, the HA concentration has been estimated to be between 65 and 400 μg/ml and the average molecular weight to be 2–4 million.

（透明质酸

HA是哺乳动物玻璃体中的主要GAG，70多年前首次从牛玻璃体中分离。38它是由重复的二糖单元（β1-4葡萄糖醛酸β1-3 N-乙酰葡萄糖胺）N构成的线性聚合物GAG。HA链可以很长，通过缠结形成网络。它与其他GAG的区别在于，它不是共价合成的，与核心蛋白相连，而且从不硫酸化。透明质酸在玻璃体内分布不均匀，在玻璃体后部皮质中浓度最高。10在成人玻璃体中，HA浓度估计在65到400之间 μg/ml，平均分子量为200-400万。）

Chondroitin sulphate proteoglycans
The repeating disaccharide unit of CS is (β1–4 glucuronic acid β1–3 N-acetylgalactosamine)n. The C-4 and/or C-6 of the N-acetylgalactosamine residues can be sulphated, modifying this repeating structure. The C-2 sulphation of the glucuronic acid occurs less frequently. The vitreous has been shown to contain two CS proteoglycans, type IX collagen (see section on collagens) and versican.15, 39 Versican is a large proteoglycan with a central domain that carries multiple CS chains. The C-terminal region contains EGF-like, lectin-like, and complement regulatory protein-like domains and the globular N-terminal region contains an HA-binding domain. The binding of versican to HA is stabilised by a glycoprotein called link protein, which has also been identified in the vitreous.39 Mutations that alter the splicing of the central CS-bearing domains of versican have been implicated in the vitreoretinopathy Wagner's syndrome.40（硫酸软骨素蛋白多糖

CS的重复双糖单元是（β1-4葡萄糖醛酸β1-3 N-乙酰半乳糖胺）N。N-乙酰半乳糖胺残基的C-4和/或C-6可以被硫酸化，从而改变这种重复结构。葡萄糖醛酸的C-2硫酸化发生的频率较低。玻璃体中含有两种CS蛋白多糖，即IX型胶原（见胶原一节）和versican。15,39 Versican是一种大型蛋白多糖，其中心结构域携带多条CS链。C端区域包含EGF样、凝集素样和补体调节蛋白样结构域，球状N端区域包含HA结合结构域。versican与HA的结合由一种叫做link protein的糖蛋白稳定，这种糖蛋白也在玻璃体中被发现。39个突变改变了云芝can中央CS承载结构域的剪接，这些突变与玻璃体视网膜病变瓦格纳综合征有关。）

Full size image
The network of (heterotypic) collagen fibrils is essential to the gel state as removal by, for example, collagenase digestion or centrifugation converts the vitreous into a viscous liquid.45 The vitreous collagen fibrils are very long, of uniform diameter (10–20 nm depending upon species), and unbranched (Figure 3a).14 Analyses by freeze-etch rotary shadowing electron microscopy showed that the collagen fibrils are arranged in bundles within the vitreous and form an extended interconnected network by branching between these bundles.46 In the young vitreous, the collagen fibrils within these bundles appear to run closely together in parallel, but are not fused. Morphological analyses suggest that the CS chains of type IX collagen play a role in both connecting together and spacing apart the collagen fibrils within these bundles.7, 47（全尺寸图像

由于胶原酶消化或离心等方法将玻璃体转化为粘性液体，因此（异型）胶原纤维网络对凝胶状态至关重要。45玻璃体胶原纤维非常长，直径均匀（10-20） 14冷冻蚀刻旋转阴影电子显微镜分析表明，胶原原纤维在玻璃体内成束排列，并通过这些束之间的分支形成一个扩展的互连网络。46在年轻的玻璃体中，这些束中的胶原纤维似乎紧密地平行排列，但没有融合。形态学分析表明，IX型胶原的CS链在连接和分隔这些束中的胶原原纤维方面起作用。）

It occurs in approximately 25% of the population during their lifetime（25%的人会在一生中玻璃体后脱离）

Vitreous liquefaction
The human vitreous humour undergoes an inevitable process of liquefaction (or syneresis) with ageing. Studies by Balazs and Denlinger10 showed that liquid vitreous is present after the age of 4 years with around 20% of the total vitreous volume consisting of liquid vitreous by 14–18 years of age. After the age of 40 years, there is a steady increase in liquid vitreous with a concomitant decrease in gel volume. More than half of the vitreous is liquid by the age of 80–90 years. The liquefaction process does not occur uniformly within the vitreous cavity. The pockets of liquid form in the central vitreous where they enlarge and coalesce.

（玻璃体液化

随着年龄的增长，人类的玻璃体液不可避免地会发生液化（或脱水）。Balazs和Denlinger10的研究表明，4岁后会出现液态玻璃体，14-18岁时，液态玻璃体占玻璃体总体积的20%左右。40岁以后，液体玻璃体的数量稳步增加，同时凝胶的体积也随之减少。超过一半的玻璃体在80-90岁时是液态的。玻璃体腔内的液化过程并不均匀。液体囊在玻璃体中央形成，并在那里扩大和合并。）

Reference：

【1】Age-related changes on the surface of vitreous collagen fibrils

【2】猪喉软骨硫酸软骨素的制备和自由基清除活性 - 道客巴巴

【3】Glycosaminoglycans from bovine eye vitreous humour and interaction with collagen type II - PMC

【4】Vitrectomy for primary symptomatic vitreous opacities: an evidence-based review | Eye

【5】Adult vitreous structure and postnatal changes

【6】[Histochemistry of hyaluronic acid of the bovine vitreous body by electronmicroscopy] - PubMed

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