氧气与角膜接触镜配戴
作者：王建华 Desmond Fonn Renee Du Toit
单位：加拿大滑铁泸大学视光学院角膜接触镜研究中心(加拿大，N2L 3G1)
关键词：
眼视光学杂志/990322[摘要]全球大约有八千万人(约占总人口的1.5%)在配戴角膜接触镜，镜片的透氧性及配戴角膜接触镜后角膜的获氧状态是保证配戴安全性和有效性的关键。角膜需要多种营养物质以保证其正常的代谢功能，氧气是其中是重要的部分，只有在充分氧供的状态下，角膜才能保持稳定的78%的水合状态，保证角膜透明性。为了进一步了解氧气与角膜接触镜配戴的关系，本文着重对角膜接触镜所致的角膜缺氧的主要表现及角膜接触镜的透氧性能及其表达指标作一综述。
配戴角膜接触镜后，角膜的氧供明显减少，特别在闭眼状态下氧供减少尤其明显，角膜接触镜引起的角膜缺氧变化主要表现为：①角膜上皮：角膜上皮水肿，即因细胞间隙中水液充盈而发生的微囊样水肿，水肿明显时会影响视力并使角膜的敏感性下降；②角膜基质：角膜基质水肿达5%以上即可从裂隙灯检查中发现，主要表现为条纹或皱褶，长期慢性水肿会诱发角膜新生血管的发生，逐步发生角膜疤痕、屈光改变等一系列问题；③角膜内皮：慢性角膜缺氧最终会导致角膜内皮细胞形态的改变，而且无法代偿。保持角膜功能的最低需氧量称为“临界氧”，理想的角膜接触镜应该是通过该镜片后到达角膜面的氧供超过临界氧。
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角膜接触镜的透氧性能表达指标主要有：透氧性(oxygen permeability,Dk)、氧传递性(oxygen transmissibility,Dk/t)和等效氧(equivalent oxygen permeability,EOP)，根据近期的研究结果，只有镜片的Dk/t高于(87.0+3.3)×10-9(cmXmlo2/secXmlXmmHg)或EOP达到17.9%，才能保证角膜获得临界氧，目前的日戴镜片的Dk/t为(24.1+2.7)×10-9(cmXmlo2/secXmlXmmHg)或EOP达到9.9%，所以不能用于长戴，而只能安全用于日戴。80年代初期，研究者致力于RGP镜片材料的开发，添加了硅和氟成分，从而极大提高了RGP镜片材料的透氧性，使得角膜接触镜长戴成为可能，并用于白内障术后等特殊镜片配戴选择。根据文献报道，日戴人群中角膜溃疡的发生率为0.04%，长戴人群中发生率大约为0.21%，长戴者发生率为日戴者的10～15倍，其主要原因是因为在软镜长戴过程中出现缺氧而导致角膜溃疡的发生。
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新一代高透氧的角膜接触镜开始出现，其透氧性可以高达(100～175)×10-9(cmXmlo2/secXmlXmmHg),含水量为26%～34%，据初步临床测试，过夜长戴后，角膜的水肿只达2.2%(非戴镜眼为1.8%)。当然理想的角膜接触镜除了高透氧性外，还需具备舒适、抗沉淀物、方便等特性。
Oxygen and Contact Lens Wear
Jianhua Wang,BA Med;
Desmond Fonn,Dip Optom,Moptom;Renee Du Toit,Dip Optom,MPhil
AbstractIn this article we review the role of oxygen and contact lens wear related to the metabolic processes of the cornea.The critical oxygen requirement of the cornea for maintenance of its normal hydration level to ensure transparency is discussed,as well as the subsequent reversible and irreversible changes to the corneal layers if this requirement is not met.We review the concept of oxygen transmission and its application to rigid gas permeable and soft contact lens material.Corneal responses to induced hypoxia related to extended wear of contact lenses as well as other complications,such as infection,are discussed.In conclusion,we comment on the oxygen performance of a new generation of silicone hydrogel contact lens materials and the future of extended wear.
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1 Introduction
There are approximately 80 million contact lens wearers world-wide which represents about 1.5% of the world's population.Between 5% and 12% of people in most developed nations use contact lenses and approximately 80%～90% of these people wear soft hydrophylic lenses.Soft lenses are generally more comfortable and therefore adaptation is easier,although rigid gas permeable (RGP) lenses supply much more oxygen to the cornea through transmission.
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Contact lenses provide safe and effective vision correction if appropriate materials,lens designs and systems are prescribed.In addition patients have to wear and care for lenses appropriately to minimise the risks of complications.Some lens wearers however,find it inconvenient to insert,remove and care for their lenses on a daily basis and would like the convenience of “permanent" vision correction.This is probably why approximately 10% of contact lens weaters use their lenses on an extended wear basis,regularly sleeping with the lenses one to 6 nights per week.The majority of practitioners and patients are however concerned about the safety of extended wear and many practitioners are still reluctant to prescribe this mode of lens wear[1].
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History has shown that extended wear is far from problem-free.One of the problems with soft contact lens extended wear has been corneal hypoxia induced by low oxygen transmission of contact lenses.The combination of reduced oxygen levels under the closed lid,with the restriction on available oxygen created by the presence of a low transmissible contact lens produces extended periods of hypoxia.Physiological changes of the cornea arise from hypoxia and may have both reversible and irreversible effects.To minimise these effects it is important to increase oxygen transmissibillity of lens materials[2].Until recently this was only possible with RGP lenses.
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2 Corneal oxgyen supply and metabolic process
The cornea requires a variety of nutrients for metabolic function and oxygen is probably the most important.Under aerobic conditions corneal metabolism generates sufficient energy for deturgence i.e.the cornea remains at a constant 78% hydration level which ensures transparency.Another reason for transparency is the fact that the cornea is avascular,unlike most tissues.It cannot therefore rely upon blood supply to transport oxygen and the other necessary nutrients to the site of metabolic activity.The aqueous is the principal source of the majority of metabolites such as glucose,amino acids,vitamins and minerals.
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While the eye is open,the atmosphere is the major source of corneal oxygen by diffusion through the tear layer.The concentration of oxygen as a percentage of the atmosphere is 21% but this expression of oxygen may be misleading because it ignores pressure.Another term that is frequently used to represent oxygen supply is partial pressure (PO2) The partial pressure of oxygen at sea-level is 155mmHg but at the top of Mt Everest,for example,it decreases to 53mmHg.Yet the concentration for both of those levels is 21%.
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During eye closure,atmospheric oxygen is essentially eliminated and the cornea has to derive oxygen from other ocular sources.These are the limbal and deeper cilliary blood vessels but the bulk of the oxygen for epithelial needs is derived from the palpebral conjunctiva.The aqueous supplies oxygen to the endothelium which is more critical when the eye is closed.The PO2 levels within the blood vessels of the palpebral conjunctiva and aqueous at the endothelial surface is approximately 55mmHg[3～5].This translates to an oxygen concentration of about 7% which means that the cornea has to function under anaerobic conditions during eye closure.Contact lens wear essentially simulates this condition,particularly if the lens has low oxygen transmission.
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Anaerobic metabolism results in an energy reduction of about 90% compared to aerobic metabolism.This translates to an inefficiency of expulsion of the by-products of metabolism such as lactate,which is an important component in the etiology of corneal edema[6].Lactic acid accumulation induces increased osmotic pressure of the corneal stroma resulting in imbition of fluid.Lactic acid,in combination with carbon dioxide build-up,causes acidosis[7]Hypoxia and therefore anaerobic metabolism results in a lower yield of adenosine triphosphate (energy) which decreases the cornea's fluid pumping function in the epithelium and endothelium.This results in additional corneal swelling[8].
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3 Effects of contact lens induced corneal hypoxia
If a contact lens is worn oxygen transmission to the corneal may be significantly reduced,especially during eye closure,and the following changes may occur:
3.1 Epithelium
Epithelial edema,sometimes referred to as microcystic edema,is formed by intercellular fluid filled spaces.This can be caused by contact lens wear or exposure to hypotonic conditions.Paradoxically neither epithelial edema or acute exposure to hypoxia increases epithelial thickness however long term wear of contact lenses has been shown to cause epithelial thinning.If significant microcystic edema occurs epithlial transparency will decrease and this will affect vision.Other long term effects of contact lens wear on the epithelium include.Decreased cellular production and enlarged cells,the formation of microcysts/vacuoles[9];compromised cell junctional integrity[10];decreased exfoliation[11]increased fragility[12];reduced sensitivity[13].
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3.2 Stroma
Although significant amounts of stromal swelling are easily detected with a biomicroscope,vision is usually unaffected.If vision is affected it is likely to be from the associated epithelial edema.Stromal edema usually manifests as striae in the central posterior layers when corneal swelling reaches 5%[13].When swelling reaches 10% (which only usually occurs with extended wear) black lines or endothelial folds are observed.Overnight corneal edema which can be as high as 18%～20% will decrease during the day when the eye is open.Depending on the amount of overnight swelling,it will often be less than 5% during the day and therefore go undetected if the patient is not examined early in the morning.Stromal edema from rigid lens wear is usually confined to the central corneal area[14].Soft lens induced swelling is more evenly distributed across the cornea but there is slightly more swelling centrally than peripherally because of physical constraints of the limbus[15].
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Other secondary effects usually occur from chronic edema and all appear to have an hypoxic origin.These include:stromal thinning,that may be as result of a loss of collagen ground substance and stromal keratocytes[17];neovascularisation of the cornea that occurs in response to stromal softening from peripheral edema and chemotaxis[18];refractive changes,i.e.increased myopia from soft lenses[19],decreased corneal sensitivity[12]and corneal exhaustion syndrome[16].Corneal exhaustion occurs after many years of wear of PMMA lenses of low water content,thick HEMA contact lenses,both of which have very low oxygen permeability.It manifests as lens intolerance,decreased visual acuity,alterations to the spherical and cylindrical camponents of refraction,endothelial irregularity,and irregularity of anterior corneal shape[16].This condition is extremely rare especially as the majority of lenses that are currently prescribed are sufficiently permeable to avoid this problem.
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3.3 Endothelium
One of the acute effects of contact lens wear is transient endothelial oedema,which is commonly referred to as `blebs'.Even though the bleb response is inversely proportional to the oxygen transmissibility of the contact lens,it may be due to the indirect effects of hypoxia.Carbon dioxide build up in the cornea from anaerobic metabolism resulting from hypoxia could be responsible for the formation of blebs.The chronic effects of hypoxia may have much more important consequences on the corneal endothelium.While endothelial cell density does not undergo a significant effect from long-term contact lens wear,the shape (pleomorphism) and size (polymegethism) of endothelial cells can be dramatically altered[20].Low oxygen permeability lenses and extended-wear are associated with a greater degree of polymegethism[21].Recovery from polymegethism appears to be slow,if at all.
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4 Critical oxygen needs of the cornea
When the cornea is exposed to the atmosphere without having worn a contact lens,it will consume oxygen at the rate of about 5:1O2/cm2/hr.However this rate increases dramatically when the eye is subjected to hypoxia while wearing a contact lens and/or eye closure.This alteration in consumption is an index of the reduced oxygen effect on the cornea.It provides a criterion of how much oxygen requirement.Other indices of estimating the critical oxygen reduction is required to minimally affect this function and is termed the “critical” oxygen requirement are corneal swelling,glycogen depletion from the epithelium and endothelium bleb response.Since these indices reveal different critical amounts,it makes the level of oxygen required to avoid corneal “malfunction" debatable.
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5 Oxygen transmission of contact lenses
Oxygen transmission can be measured directly or indirectly.A direct method of measuring the oxygen permeability (Dk) of a lens was described by Fatt and St Helen in 1971[22].In engineering terms,the Dk,or`oxygen permeability',of a material is determined by how much gas flows through a unit amount of material across a unit partial pressure gradient.It is therefore a constant for a given material.The unit of measurement is the Barrer,which corresponds to (cm2/sec) (mlo2/ml×mmHg)[23].The oxygen transmissibility (Dk/t) is the permeability (Dk) divided by the thickness (t) of the given lens.
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An indirect method for measuring oxygen transmission is the Equivalent Oxygen Percentage Technique (EOP).The EOP value represents the percentage of oxygen or oxygen tension in the tear layer that has effectively been transmitted by a contact lens.The EOP represents an oxgyen `thirst' of the cornea that is created by a contact lens which is epuivalent to a known oxygen concentration in a gas mixture that the cornea was exposed to.EOP is measured in vivo,therefore it can be used as a method to determine how much oxygen “debt" was created in an individual cornea when wearing a specific lens[24].In the open-eye,EOP and oxygen permeability or transmissibility (Dk/L) values are highly correlated.In the closed-eye state,however these may be significantly influenced by other factors,such as corneal temperature and pH value[25].
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Oxygen transmissibility of a soft contact lens is associated with lens water content and thickness.Oxygen passes through the water phase of a soft lens.Thus the higher the water content,the greater the oxgyen permeability;however,oxygen permeability of water is limited which is why soft contact lenses have not been sufficiently transmissible for extended wear.Another factor in oxygen transmissibility of a lens to consider is lens profile thickness.While center thickness values are usually specified,transmissibility across the lens can vary considerably if there are large differences in thickness across the lens[26].
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Holden and Mertz performed one of the key studies in the estimation of critical oxygen requirement of the cornea in 1984[33].They calculated that the critical lens oxygen transmissibility required to avoid lens induced cornea edema,under daily wear conditions was (24.1±2.7)×10-9(cm×mlO2)/(sec×ml×mmHg)and EOP was 9.9%.The lens transmissibility needed to limit overnight corneal oedema to 4% (edema without wearing a contact lens) was calculated to be (87.0±3.3)×10-9(cm×mlO2)/(sec×ml×mmHg)and EOP was 17.9%.Current soft contact lenses can meet the requirement for daily wear,but not for extended wear.Holden et al[7]also determined that providing a human cornea with more than 10% oxygen in a gas mixture was sufficient to avoid corneal swelling.In early animal studies reducing the oxygen concentration below 5% caused a depletion of epithelial glycogen[27].
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In the early eighties,most of the material development was focused on rigid gas permeable (RGP) lenses.The addition of siloxane and later fluorine components to RGP materials enabled the manufacture of lenses with superior Dk/t,Refinements to RGP materials,in which the Dk/t was balanced with other desirable properties,led to lenses which could be worn overnight with an encouraging degree of success.The first reports of overnight use with RGP lenses appeared in 1984 for aphakia[28],and 1985 for cosmetic wear.RGP lenses seemed a pronising alternative,offering ease of handling,ease of care,durability,high Dk/t,compatible surface characteristics,good tear exchange,deposit resistance,decreased limbal vessel response,and superior visual performance in many cases[2].
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Although the critical oxygen requirement of even extended wear can be reached with RGP lens materials,these lenses can cause other problems which are predominantly related to the mechanical properties of the lens.These complications include:discomfort which can lead to discontinuation of lens wear[2,29],3&9 o'clock staining,lens adherence and corneal distortion.
Infection
Poggio et al[30]found the annualized incidence of ulcerative keratitis was 20.9 per 10,000 persons using extended-wear soft contact lenses for cosmetic purposes and 4.1 per 10,000 persons using daily-wear soft contact lenses for cosmetic purposes.According to Schein et al[31],extended wear of contact lenses presents a 10 to 15 times greater risk of developing microbial keratitis than wearing lenses on a daily wear basis.
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It is now a well established fact that all soft contact lenses cause hypoxia during overnight wear[1,2,7,30,31]and extended wear of soft lenses is more likely to cause microbial keratitis and contact lens associated peripheral ulcers.It appears that hypoxia is associated with Pseudomonas Aeruginosa (PA) binding to human epithelial cells (in vitro) as a result of wearing contact lenses[32].lmayasu and co-workers[33]reported the same results in rabbits.The conclusion from both studies is that hypoxia from wearing low Dk/t lenses produces changes to the epithelial cells which facilitates PA binding.It has also been shown that PA is the most common pathogen associated with microbial keratitis from soft lens extended wear[34].
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Under closed eye conditions,tear secretion and lens movement decreases resulting in very little or no tear exchange.It has been shown that extended contact lens wear can substantially increase corneal epithelial permeability to fluorescein[35].This is presumably due to corneal hypoxia and reduced tear exchange which suggests that these factors are responsible for altering the barrier function of corneal epithelium and may make the cornea more susceptible to infections[36].
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6 The future
Convenience and safety are major motivating factors in the choice of a mode of vision correction for refractive errors.Extended wear of contact lenses is associated with greater convenience than daily wear,but questions remain concerning the safety and risks associated with this modality.Studies collectively suggest that corneal hypoxia during extended wear is a potential causative mechanism in infectious keratitis which implies that a highly oxygen permeable soft lens may minimise or solve this problem.To improve oxygen supply,overall lens thickness may be reduced,lens movement and water content can be increased.However,these efforts have not provided sufficient oxygen to meet corneal requirements for safe extended wear.
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Recently,new high-Dk soft lens materials,which contain both hydrophilic and silicone components have become available.The hydrogel component provides many of the desirable aspects of traditional soft lenses,such as comfort,conformity and surface compatibility.The silicone component provides a transport route for oxygen.Two silicone hydrogel contact lenses have recently become available with permeability values ranging from (100～175)×10-11and water contents ranging from 26%～34%.Fonn and his colleagues found 2.2% corneal swelling immediately on eye opening after overnight wear of theses lenses,compared to 1.8% in the non lens wearing control eyes.
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However,it should be remembered that there are other important considerations for successful contact lens wear than oxygen transmissibility,such as lens comfort,deposit resistance,vision,fit and convenience.
From Centre for Conact Lens Reseearch,School of Optometry,University of Waterloo,Canada,N2L 3G1
作者单位：加拿大滑铁泸大学视光学院角膜接触镜研究中心(加拿大，N2L 3G1)
7 References
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[10] O'Leary DJ,Madgewick R,Wallace J,et al.Size and number of epithelial cells washed from the cornea after contact lens wear.Optom Vis Sci,1998,75∶692～696
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[18] Spoor TC,Hartel WC,Wynn P,et al.Complications of continuous wear soft contact lenses in a non-referral population.Arch Ophthalmol,1994,102∶1312～1313
[19] Harris MG,Sarver MD,Polse KA.Corneal curvature and refractive error changes associated with wearing hydrogel contact lenses.Am J Opton Physiol Opt 1975,52∶313～319
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[21] Holden B,Swarbrick HA,Sweeney DF,et al.Strategies for minimizing the ocular effect of extended contact lens wear-a statistical analysis.Am J Optom Physiol Opt,1987,64∶781～789
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[28] Benjamin WJ,Simons MH.Extended wear of oxygen permeable rigid lenses in aphakia.ICLE,1984,11∶547～561
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[32] Ren DH,Petroll WM,Jester JV,et al.The relationship between contact lens oxygen permeability and binding of pseudomouas aeruginosa to human corneal epithelial cells after overnight and extended wear.CLAO J,1999,25∶80～100
[33] Imaysau M,Petroll WM,Jester JV,et al.The relation between contact lens oxygen transmissibility and binding of Pseudomonas aeruginosa to the cornea after overnight wear.Ophthalmology,1994,101∶371～388
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[35] McNamara N,Fusaro R,Brand RJ,et al.Epithelial permeability reflects subclinical effects of contact lens wear.Br J Ophthalmol，1998;82∶376～381
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(收稿：1999-08-04), 百拇医药
单位：加拿大滑铁泸大学视光学院角膜接触镜研究中心(加拿大，N2L 3G1)
关键词：
眼视光学杂志/990322[摘要]全球大约有八千万人(约占总人口的1.5%)在配戴角膜接触镜，镜片的透氧性及配戴角膜接触镜后角膜的获氧状态是保证配戴安全性和有效性的关键。角膜需要多种营养物质以保证其正常的代谢功能，氧气是其中是重要的部分，只有在充分氧供的状态下，角膜才能保持稳定的78%的水合状态，保证角膜透明性。为了进一步了解氧气与角膜接触镜配戴的关系，本文着重对角膜接触镜所致的角膜缺氧的主要表现及角膜接触镜的透氧性能及其表达指标作一综述。
配戴角膜接触镜后，角膜的氧供明显减少，特别在闭眼状态下氧供减少尤其明显，角膜接触镜引起的角膜缺氧变化主要表现为：①角膜上皮：角膜上皮水肿，即因细胞间隙中水液充盈而发生的微囊样水肿，水肿明显时会影响视力并使角膜的敏感性下降；②角膜基质：角膜基质水肿达5%以上即可从裂隙灯检查中发现，主要表现为条纹或皱褶，长期慢性水肿会诱发角膜新生血管的发生，逐步发生角膜疤痕、屈光改变等一系列问题；③角膜内皮：慢性角膜缺氧最终会导致角膜内皮细胞形态的改变，而且无法代偿。保持角膜功能的最低需氧量称为“临界氧”，理想的角膜接触镜应该是通过该镜片后到达角膜面的氧供超过临界氧。
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角膜接触镜的透氧性能表达指标主要有：透氧性(oxygen permeability,Dk)、氧传递性(oxygen transmissibility,Dk/t)和等效氧(equivalent oxygen permeability,EOP)，根据近期的研究结果，只有镜片的Dk/t高于(87.0+3.3)×10-9(cmXmlo2/secXmlXmmHg)或EOP达到17.9%，才能保证角膜获得临界氧，目前的日戴镜片的Dk/t为(24.1+2.7)×10-9(cmXmlo2/secXmlXmmHg)或EOP达到9.9%，所以不能用于长戴，而只能安全用于日戴。80年代初期，研究者致力于RGP镜片材料的开发，添加了硅和氟成分，从而极大提高了RGP镜片材料的透氧性，使得角膜接触镜长戴成为可能，并用于白内障术后等特殊镜片配戴选择。根据文献报道，日戴人群中角膜溃疡的发生率为0.04%，长戴人群中发生率大约为0.21%，长戴者发生率为日戴者的10～15倍，其主要原因是因为在软镜长戴过程中出现缺氧而导致角膜溃疡的发生。
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新一代高透氧的角膜接触镜开始出现，其透氧性可以高达(100～175)×10-9(cmXmlo2/secXmlXmmHg),含水量为26%～34%，据初步临床测试，过夜长戴后，角膜的水肿只达2.2%(非戴镜眼为1.8%)。当然理想的角膜接触镜除了高透氧性外，还需具备舒适、抗沉淀物、方便等特性。
Oxygen and Contact Lens Wear
Jianhua Wang,BA Med;
Desmond Fonn,Dip Optom,Moptom;Renee Du Toit,Dip Optom,MPhil
AbstractIn this article we review the role of oxygen and contact lens wear related to the metabolic processes of the cornea.The critical oxygen requirement of the cornea for maintenance of its normal hydration level to ensure transparency is discussed,as well as the subsequent reversible and irreversible changes to the corneal layers if this requirement is not met.We review the concept of oxygen transmission and its application to rigid gas permeable and soft contact lens material.Corneal responses to induced hypoxia related to extended wear of contact lenses as well as other complications,such as infection,are discussed.In conclusion,we comment on the oxygen performance of a new generation of silicone hydrogel contact lens materials and the future of extended wear.
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1 Introduction
There are approximately 80 million contact lens wearers world-wide which represents about 1.5% of the world's population.Between 5% and 12% of people in most developed nations use contact lenses and approximately 80%～90% of these people wear soft hydrophylic lenses.Soft lenses are generally more comfortable and therefore adaptation is easier,although rigid gas permeable (RGP) lenses supply much more oxygen to the cornea through transmission.
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Contact lenses provide safe and effective vision correction if appropriate materials,lens designs and systems are prescribed.In addition patients have to wear and care for lenses appropriately to minimise the risks of complications.Some lens wearers however,find it inconvenient to insert,remove and care for their lenses on a daily basis and would like the convenience of “permanent" vision correction.This is probably why approximately 10% of contact lens weaters use their lenses on an extended wear basis,regularly sleeping with the lenses one to 6 nights per week.The majority of practitioners and patients are however concerned about the safety of extended wear and many practitioners are still reluctant to prescribe this mode of lens wear[1].
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History has shown that extended wear is far from problem-free.One of the problems with soft contact lens extended wear has been corneal hypoxia induced by low oxygen transmission of contact lenses.The combination of reduced oxygen levels under the closed lid,with the restriction on available oxygen created by the presence of a low transmissible contact lens produces extended periods of hypoxia.Physiological changes of the cornea arise from hypoxia and may have both reversible and irreversible effects.To minimise these effects it is important to increase oxygen transmissibillity of lens materials[2].Until recently this was only possible with RGP lenses.
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2 Corneal oxgyen supply and metabolic process
The cornea requires a variety of nutrients for metabolic function and oxygen is probably the most important.Under aerobic conditions corneal metabolism generates sufficient energy for deturgence i.e.the cornea remains at a constant 78% hydration level which ensures transparency.Another reason for transparency is the fact that the cornea is avascular,unlike most tissues.It cannot therefore rely upon blood supply to transport oxygen and the other necessary nutrients to the site of metabolic activity.The aqueous is the principal source of the majority of metabolites such as glucose,amino acids,vitamins and minerals.
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While the eye is open,the atmosphere is the major source of corneal oxygen by diffusion through the tear layer.The concentration of oxygen as a percentage of the atmosphere is 21% but this expression of oxygen may be misleading because it ignores pressure.Another term that is frequently used to represent oxygen supply is partial pressure (PO2) The partial pressure of oxygen at sea-level is 155mmHg but at the top of Mt Everest,for example,it decreases to 53mmHg.Yet the concentration for both of those levels is 21%.
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During eye closure,atmospheric oxygen is essentially eliminated and the cornea has to derive oxygen from other ocular sources.These are the limbal and deeper cilliary blood vessels but the bulk of the oxygen for epithelial needs is derived from the palpebral conjunctiva.The aqueous supplies oxygen to the endothelium which is more critical when the eye is closed.The PO2 levels within the blood vessels of the palpebral conjunctiva and aqueous at the endothelial surface is approximately 55mmHg[3～5].This translates to an oxygen concentration of about 7% which means that the cornea has to function under anaerobic conditions during eye closure.Contact lens wear essentially simulates this condition,particularly if the lens has low oxygen transmission.
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Anaerobic metabolism results in an energy reduction of about 90% compared to aerobic metabolism.This translates to an inefficiency of expulsion of the by-products of metabolism such as lactate,which is an important component in the etiology of corneal edema[6].Lactic acid accumulation induces increased osmotic pressure of the corneal stroma resulting in imbition of fluid.Lactic acid,in combination with carbon dioxide build-up,causes acidosis[7]Hypoxia and therefore anaerobic metabolism results in a lower yield of adenosine triphosphate (energy) which decreases the cornea's fluid pumping function in the epithelium and endothelium.This results in additional corneal swelling[8].
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3 Effects of contact lens induced corneal hypoxia
If a contact lens is worn oxygen transmission to the corneal may be significantly reduced,especially during eye closure,and the following changes may occur:
3.1 Epithelium
Epithelial edema,sometimes referred to as microcystic edema,is formed by intercellular fluid filled spaces.This can be caused by contact lens wear or exposure to hypotonic conditions.Paradoxically neither epithelial edema or acute exposure to hypoxia increases epithelial thickness however long term wear of contact lenses has been shown to cause epithelial thinning.If significant microcystic edema occurs epithlial transparency will decrease and this will affect vision.Other long term effects of contact lens wear on the epithelium include.Decreased cellular production and enlarged cells,the formation of microcysts/vacuoles[9];compromised cell junctional integrity[10];decreased exfoliation[11]increased fragility[12];reduced sensitivity[13].
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3.2 Stroma
Although significant amounts of stromal swelling are easily detected with a biomicroscope,vision is usually unaffected.If vision is affected it is likely to be from the associated epithelial edema.Stromal edema usually manifests as striae in the central posterior layers when corneal swelling reaches 5%[13].When swelling reaches 10% (which only usually occurs with extended wear) black lines or endothelial folds are observed.Overnight corneal edema which can be as high as 18%～20% will decrease during the day when the eye is open.Depending on the amount of overnight swelling,it will often be less than 5% during the day and therefore go undetected if the patient is not examined early in the morning.Stromal edema from rigid lens wear is usually confined to the central corneal area[14].Soft lens induced swelling is more evenly distributed across the cornea but there is slightly more swelling centrally than peripherally because of physical constraints of the limbus[15].
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Other secondary effects usually occur from chronic edema and all appear to have an hypoxic origin.These include:stromal thinning,that may be as result of a loss of collagen ground substance and stromal keratocytes[17];neovascularisation of the cornea that occurs in response to stromal softening from peripheral edema and chemotaxis[18];refractive changes,i.e.increased myopia from soft lenses[19],decreased corneal sensitivity[12]and corneal exhaustion syndrome[16].Corneal exhaustion occurs after many years of wear of PMMA lenses of low water content,thick HEMA contact lenses,both of which have very low oxygen permeability.It manifests as lens intolerance,decreased visual acuity,alterations to the spherical and cylindrical camponents of refraction,endothelial irregularity,and irregularity of anterior corneal shape[16].This condition is extremely rare especially as the majority of lenses that are currently prescribed are sufficiently permeable to avoid this problem.
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3.3 Endothelium
One of the acute effects of contact lens wear is transient endothelial oedema,which is commonly referred to as `blebs'.Even though the bleb response is inversely proportional to the oxygen transmissibility of the contact lens,it may be due to the indirect effects of hypoxia.Carbon dioxide build up in the cornea from anaerobic metabolism resulting from hypoxia could be responsible for the formation of blebs.The chronic effects of hypoxia may have much more important consequences on the corneal endothelium.While endothelial cell density does not undergo a significant effect from long-term contact lens wear,the shape (pleomorphism) and size (polymegethism) of endothelial cells can be dramatically altered[20].Low oxygen permeability lenses and extended-wear are associated with a greater degree of polymegethism[21].Recovery from polymegethism appears to be slow,if at all.
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4 Critical oxygen needs of the cornea
When the cornea is exposed to the atmosphere without having worn a contact lens,it will consume oxygen at the rate of about 5:1O2/cm2/hr.However this rate increases dramatically when the eye is subjected to hypoxia while wearing a contact lens and/or eye closure.This alteration in consumption is an index of the reduced oxygen effect on the cornea.It provides a criterion of how much oxygen requirement.Other indices of estimating the critical oxygen reduction is required to minimally affect this function and is termed the “critical” oxygen requirement are corneal swelling,glycogen depletion from the epithelium and endothelium bleb response.Since these indices reveal different critical amounts,it makes the level of oxygen required to avoid corneal “malfunction" debatable.
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5 Oxygen transmission of contact lenses
Oxygen transmission can be measured directly or indirectly.A direct method of measuring the oxygen permeability (Dk) of a lens was described by Fatt and St Helen in 1971[22].In engineering terms,the Dk,or`oxygen permeability',of a material is determined by how much gas flows through a unit amount of material across a unit partial pressure gradient.It is therefore a constant for a given material.The unit of measurement is the Barrer,which corresponds to (cm2/sec) (mlo2/ml×mmHg)[23].The oxygen transmissibility (Dk/t) is the permeability (Dk) divided by the thickness (t) of the given lens.
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An indirect method for measuring oxygen transmission is the Equivalent Oxygen Percentage Technique (EOP).The EOP value represents the percentage of oxygen or oxygen tension in the tear layer that has effectively been transmitted by a contact lens.The EOP represents an oxgyen `thirst' of the cornea that is created by a contact lens which is epuivalent to a known oxygen concentration in a gas mixture that the cornea was exposed to.EOP is measured in vivo,therefore it can be used as a method to determine how much oxygen “debt" was created in an individual cornea when wearing a specific lens[24].In the open-eye,EOP and oxygen permeability or transmissibility (Dk/L) values are highly correlated.In the closed-eye state,however these may be significantly influenced by other factors,such as corneal temperature and pH value[25].
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Oxygen transmissibility of a soft contact lens is associated with lens water content and thickness.Oxygen passes through the water phase of a soft lens.Thus the higher the water content,the greater the oxgyen permeability;however,oxygen permeability of water is limited which is why soft contact lenses have not been sufficiently transmissible for extended wear.Another factor in oxygen transmissibility of a lens to consider is lens profile thickness.While center thickness values are usually specified,transmissibility across the lens can vary considerably if there are large differences in thickness across the lens[26].
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Holden and Mertz performed one of the key studies in the estimation of critical oxygen requirement of the cornea in 1984[33].They calculated that the critical lens oxygen transmissibility required to avoid lens induced cornea edema,under daily wear conditions was (24.1±2.7)×10-9(cm×mlO2)/(sec×ml×mmHg)and EOP was 9.9%.The lens transmissibility needed to limit overnight corneal oedema to 4% (edema without wearing a contact lens) was calculated to be (87.0±3.3)×10-9(cm×mlO2)/(sec×ml×mmHg)and EOP was 17.9%.Current soft contact lenses can meet the requirement for daily wear,but not for extended wear.Holden et al[7]also determined that providing a human cornea with more than 10% oxygen in a gas mixture was sufficient to avoid corneal swelling.In early animal studies reducing the oxygen concentration below 5% caused a depletion of epithelial glycogen[27].
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In the early eighties,most of the material development was focused on rigid gas permeable (RGP) lenses.The addition of siloxane and later fluorine components to RGP materials enabled the manufacture of lenses with superior Dk/t,Refinements to RGP materials,in which the Dk/t was balanced with other desirable properties,led to lenses which could be worn overnight with an encouraging degree of success.The first reports of overnight use with RGP lenses appeared in 1984 for aphakia[28],and 1985 for cosmetic wear.RGP lenses seemed a pronising alternative,offering ease of handling,ease of care,durability,high Dk/t,compatible surface characteristics,good tear exchange,deposit resistance,decreased limbal vessel response,and superior visual performance in many cases[2].
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Although the critical oxygen requirement of even extended wear can be reached with RGP lens materials,these lenses can cause other problems which are predominantly related to the mechanical properties of the lens.These complications include:discomfort which can lead to discontinuation of lens wear[2,29],3&9 o'clock staining,lens adherence and corneal distortion.
Infection
Poggio et al[30]found the annualized incidence of ulcerative keratitis was 20.9 per 10,000 persons using extended-wear soft contact lenses for cosmetic purposes and 4.1 per 10,000 persons using daily-wear soft contact lenses for cosmetic purposes.According to Schein et al[31],extended wear of contact lenses presents a 10 to 15 times greater risk of developing microbial keratitis than wearing lenses on a daily wear basis.
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It is now a well established fact that all soft contact lenses cause hypoxia during overnight wear[1,2,7,30,31]and extended wear of soft lenses is more likely to cause microbial keratitis and contact lens associated peripheral ulcers.It appears that hypoxia is associated with Pseudomonas Aeruginosa (PA) binding to human epithelial cells (in vitro) as a result of wearing contact lenses[32].lmayasu and co-workers[33]reported the same results in rabbits.The conclusion from both studies is that hypoxia from wearing low Dk/t lenses produces changes to the epithelial cells which facilitates PA binding.It has also been shown that PA is the most common pathogen associated with microbial keratitis from soft lens extended wear[34].
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Under closed eye conditions,tear secretion and lens movement decreases resulting in very little or no tear exchange.It has been shown that extended contact lens wear can substantially increase corneal epithelial permeability to fluorescein[35].This is presumably due to corneal hypoxia and reduced tear exchange which suggests that these factors are responsible for altering the barrier function of corneal epithelium and may make the cornea more susceptible to infections[36].
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6 The future
Convenience and safety are major motivating factors in the choice of a mode of vision correction for refractive errors.Extended wear of contact lenses is associated with greater convenience than daily wear,but questions remain concerning the safety and risks associated with this modality.Studies collectively suggest that corneal hypoxia during extended wear is a potential causative mechanism in infectious keratitis which implies that a highly oxygen permeable soft lens may minimise or solve this problem.To improve oxygen supply,overall lens thickness may be reduced,lens movement and water content can be increased.However,these efforts have not provided sufficient oxygen to meet corneal requirements for safe extended wear.
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Recently,new high-Dk soft lens materials,which contain both hydrophilic and silicone components have become available.The hydrogel component provides many of the desirable aspects of traditional soft lenses,such as comfort,conformity and surface compatibility.The silicone component provides a transport route for oxygen.Two silicone hydrogel contact lenses have recently become available with permeability values ranging from (100～175)×10-11and water contents ranging from 26%～34%.Fonn and his colleagues found 2.2% corneal swelling immediately on eye opening after overnight wear of theses lenses,compared to 1.8% in the non lens wearing control eyes.
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However,it should be remembered that there are other important considerations for successful contact lens wear than oxygen transmissibility,such as lens comfort,deposit resistance,vision,fit and convenience.
From Centre for Conact Lens Reseearch,School of Optometry,University of Waterloo,Canada,N2L 3G1
作者单位：加拿大滑铁泸大学视光学院角膜接触镜研究中心(加拿大，N2L 3G1)
7 References
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(收稿：1999-08-04), 百拇医药