1. 揉眼行为的机械性损伤机制与角膜结构破坏
1.1 角膜各层组织的直接物理损伤
揉眼行为对角膜的机械性损伤是多方面的，首先体现在对角膜各层组织的直接物理损害。角膜上皮层作为眼球的最外层屏障，在揉眼过程中直接承受手指或衣物等外力的摩擦和压迫。这种机械作用可导致上皮细胞的脱落，进而破坏角膜的完整性和屏障功能1。研究表明，仅15秒轻度至中度揉眼即可导致角膜上皮厚度显著减少18.4%，恢复至基线水平需要15至45分钟1。这提示即使是短暂的揉眼，也能引起上皮细胞的损伤和移位。
深层的Bowman膜（前弹力层）和角膜基质层同样受到影响。长期或反复的机械应力可能导致角膜基质层胶原纤维的排列紊乱，影响其正常的生物力学特性。角膜基质细胞（角膜细胞）的凋亡也与圆锥角膜相关，而慢性揉眼是导致角膜细胞凋亡的潜在风险因素之一2。此外，揉眼行为可能诱发角膜基质细胞产生异常的应激反应，例如机械应变可能导致WNT10A基因表达显著降低，进而影响胶原蛋白I型和XII型的生成及TGFβ1的表达，这些变化都与圆锥角膜的生物力学失效密切相关3。在极端情况下，如铅笔芯刺伤角膜后，揉眼行为甚至可能导致铅笔芯段在角膜基质层内发生二次位移和层间解剖，进一步加剧角膜损伤4。
1.2 角膜生物力学特性的改变
长期揉眼对角膜生物力学特性的影响主要表现为角膜基质的软化和局部应力集中，这与圆锥角膜等病理改变密切相关。角膜的生物力学稳定性主要依赖于其胶原纤维的结构完整性与排列方式。反复的机械应力，如揉眼，可能通过改变胶原纤维的交联强度和激活基质金属蛋白酶（MMPs）导致角膜逐渐变薄和锥形突出 56。
有限元模型研究已深入探讨了机械应力对角膜形态的影响机制。例如，一项研究构建了包含角膜五层结构及基质层中胶原纤维异质性力学行为的有限元模型，模拟了揉眼样载荷对健康角膜的影响。结果显示，揉眼对深部后基质层产生显著的张应力，而其他层受到的影响相对较小 6。这表明揉眼导致的机械损伤可能首先影响角膜深层结构，进而引发连锁反应。当角膜基质软化或基质层（特别是中后部基质）的胶原纤维结构紊乱时，即使在正常的眼内压下，也会出现锥形变形和角膜变薄的现象。软化前部角膜层并不会引起锥形变形，这进一步强调了基质层深部在维持角膜形态中的关键作用 6。
在过敏性结膜炎患者中，揉眼行为已被证实与角膜生物力学参数的改变有关。一项针对过敏性结膜炎儿童的研究发现，频繁揉眼与角膜前表面高度和前表面差异偏离的增加显著相关，这些变化通过影响地形图和生物力学指数（TBI）来介导揉眼效应 7。尽管一些研究表明，在正常眼部偶尔揉眼（例如10,500次揉搓，相当于一年内每天揉搓6次，每次5个动作）可能不会显著改变角膜的生物力学硬度 8，但这并不意味着揉眼对角膜完全无害。它可能在易感个体中（如圆锥角膜患者）加速疾病进展，或在长期、高强度揉眼中引发损伤 89。特别是对于圆锥角膜患者，揉眼被证明是导致角膜快速退化的重要因素。停止揉眼后，中央角膜厚度（CCT）的损失率降低，角膜稳定性得到维持 9。这些证据共同表明，揉眼通过机械应力改变角膜的生物力学特性，是导致或加剧角膜病变（尤其是圆锥角膜）的关键环节 51011。
2. 揉眼诱发的眼部炎症反应与免疫失衡
2.1 机械应力激活的炎症信号通路
揉眼作为一种机械刺激，不仅直接损伤眼部组织，还能通过激活特定的信号通路，诱导眼部炎症反应。近年来研究发现，机械敏感性离子通道Piezo1在结膜上皮细胞中发挥关键作用，其激活是机械应力诱发眼部炎症的重要起始环节。
当眼表受到揉搓等机械刺激时，结膜上皮细胞中的Piezo1通道被激活。这种激活会导致细胞内钙离子浓度升高。随后的细胞内信号级联反应显示，钙离子升高的信号通过p38 MAPK（丝裂原活化蛋白激酶）-CREB（cAMP反应元件结合蛋白）通路进行传递 12。具体而言，Piezo1通道的激活首先促进p38 MAPK磷酸化，进而导致CREB磷酸化。最终，这一通路诱导了多种促炎细胞因子（如IL-6和IL-8）的表达和释放 12。
体外实验证实，使用Piezo1特异性激动剂Yoda1处理人结膜上皮细胞（HConjECs），能够显著增加IL-6和IL-8的表达水平。进一步研究表明，Piezo1激活诱导的钙离子升高对IL-6的产生至关重要。通过敲低PIEZO1基因或使用Piezo1抑制剂GsMTx4，可以有效阻断Yoda1诱导的炎症反应，从而证实Piezo1在此过程中的特异性 12。
动物体内研究也支持了这一机制。将Yoda1滴眼液滴入大鼠眼部后，大鼠结膜上皮细胞中磷酸化p38 MAPK、磷酸化CREB以及IL-6的水平显著升高，并伴随有明显的嗜中性粒细胞浸润，这表明眼部炎症反应已被激活 12。这些发现共同揭示了机械应力（如揉眼）通过Piezo1通道激活结膜上皮细胞，进而诱导促炎细胞因子释放并促进炎症细胞浸润的分子机制，强调了机械刺激是眼部炎症的一个重要风险因素 12。
2.2 过敏-揉眼的恶性循环
过敏性结膜炎（AC）患者常常因为眼部瘙痒而频繁揉眼，这不仅是疾病的一种症状表现，更是一个可能加剧病情，形成恶性循环的关键环节。这种“过敏-揉眼”的恶性循环机制，涉及炎症介质的释放、组织损伤的加剧以及疾病的进一步发展。
当过敏原刺激眼部时，肥大细胞脱颗粒释放组胺、白三烯和前列腺素等炎症介质，引发眼痒、充血、水肿等过敏症状。患者为缓解不适而揉眼，然而，揉眼这一机械刺激会加剧瘙痒感，形成一个自我强化的负反馈循环。组胺的释放不仅引起瘙痒，还会导致结膜血管扩张，引起充血和水肿，使结膜炎症反应持续存在甚至恶化。
长期或频繁的揉眼对眼表组织造成持续性的物理损伤。特别是对于慢性过敏性结膜炎患者，这种机械刺激可能导致结膜上皮细胞的屏障功能受损，更容易受到过敏原和其他刺激物的侵袭。更重要的是，反复揉眼可直接损伤角膜缘干细胞。角膜缘干细胞是维持角膜上皮完整性和透明性的关键，其损伤会导致角膜上皮的愈合能力下降，可能引起角膜糜烂、溃疡，甚至影响视力。例如，春季角结膜炎（VKC）是一种严重的过敏性炎症，常伴随频繁揉眼，这被认为是VKC患者角膜并发症高发的重要原因之一，包括圆锥角膜等进行性角膜疾病 13。研究显示，VKC患者中圆锥角膜的患病率高达26.8%，而高达71%的患者可能出现异常的角膜地形图，这与揉眼行为密切相关 13。
此外，揉眼还被发现与角膜生物力学特性的改变有关。过敏性结膜炎患者的角膜生物力学参数（如角膜地形图和生物力学指数，TBI）可能会发生显著变化，这些变化与揉眼的频率和强度相关 71415。长期揉眼诱发的角膜生物力学改变，可能进一步加速圆锥角膜等角膜变形性疾病的进展，使患者面临更严重的视力损害风险 14。因此，中断“过敏-揉眼”的恶性循环，通过有效控制过敏症状、避免揉眼，对于保护眼部健康、预防和延缓角膜病变的发生发展至关重要。
3. 揉眼与圆锥角膜的关联性及病理进展
3.1 揉眼作为圆锥角膜的核心风险因素
揉眼行为被广泛认为是圆锥角膜（Keratoconus, KC）发生和发展的重要甚至核心风险因素之一 5161718。圆锥角膜是一种进行性、非炎症性的角膜扩张性疾病，其特征是角膜进行性变薄和锥形突出，导致不规则散光和视力下降 51920。流行病学数据显示，揉眼与圆锥角膜之间存在显著的关联，且这种关联性在多项研究中得到了证实。
多项系统评价和Meta分析强调了揉眼在圆锥角膜病因学中的重要作用。一项综合分析指出，揉眼的优势比（Odds Ratio, OR）为3.09（95% CI: 2.17-4.00），表明揉眼习惯者患圆锥角膜的风险是非揉眼者的三倍以上 21。另一项Meta分析报告了更高的OR值，达到3.64（95% CI: 2.02, 6.57），进一步强化了揉眼作为风险因素的证据 16。甚至有研究通过对六项病例对照研究进行汇总分析，得出揉眼与圆锥角膜的合并优势比为6.46（95% CI: 4.12-10.1）的结论，显示出极强的相关性 22。这些流行病学数据有力地支持了揉眼是圆锥角膜的重要诱发因素。
圆锥角膜的发生发展被认为是遗传易感性与环境因素共同作用的结果，而揉眼常被视为触发疾病进展的“第二打击” 18。在具有遗传倾向的个体中，揉眼带来的机械性应力可能启动或加速角膜的病理改变。此外，揉眼的频率和力度与圆锥角膜的发病率及严重程度呈现剂量-效应关系。长期、频繁且用力的揉眼，尤其是在过敏性结膜炎患者中，由于持续的瘙痒刺激，更容易导致角膜结构损伤，加速角膜变薄和锥形变性的进程 132023。研究还发现，儿童和青少年，特别是那些患有注意力缺陷多动障碍（ADHD）的男性，可能更容易出现揉眼行为，进而增加患圆锥角膜的风险 24。
值得注意的是，即使在早期或轻度的圆锥角膜病例中，避免揉眼也被认为是控制疾病进展的关键措施。这进一步佐证了揉眼在圆锥角膜病理进展中的驱动作用。因此，教育患者避免揉眼，并积极治疗引起眼痒的基础疾病（如过敏），是预防和管理圆锥角膜的重要组成部分。
3.2 机械应力驱动的角膜基质病理改变
揉眼行为通过机械应力对角膜基质造成多方面的病理改变，最终导致角膜进行性变薄与锥形突出，这是圆锥角膜病理进展的核心环节。组织学研究已深入揭示了揉眼如何破坏角膜的微观结构和生物化学平衡。
首先，揉眼产生的反复机械应力能够直接破坏角膜基质层的胶原交联结构。角膜的生物力学强度主要来源于其高度有序排列的胶原纤维及其之间的共价交联。机械应力，特别是扭曲和剪切力，可以导致这些胶原纤维的微损伤，并破坏原有的交联，从而削弱角膜的整体结构完整性。一项研究显示，在模拟揉眼的机械应变下，角膜基质中的WNT10A mRNA和蛋白表达显著降低，进而导致I型和XII型胶原蛋白的消耗及TGFβ1表达的减少 3。胶原蛋白的减少直接影响角膜的韧性和稳定性。另一项体外模型研究通过对人角膜基质施加单轴拉伸（模拟揉眼），发现Bowman层断裂数量显著增加，同时Wnt10a和Col12a1 mRNA水平降低 25，这些都是圆锥角膜早期病理变化的标志。
其次，揉眼诱导的机械应力会激活基质金属蛋白酶（MMPs），这是一类能够降解细胞外基质（ECM）蛋白的酶。在正常的生理条件下，MMPs在角膜组织重塑和伤口愈合中发挥作用，但其活性受到严格调控。然而，在揉眼等机械刺激下，MMPs的表达和活性会异常升高，打破了ECM的合成与降解平衡。研究发现，圆锥角膜患者的角膜组织和泪液中MMPs，尤其是MMP-1和MMP-9的水平显著升高 2627。机械压缩（模拟揉眼）已被证实能导致人角膜成纤维细胞中MMP-1和MMP-9等ECM降解相关基因的表达显著上调 28。其中，MMP-9被认为在感染性角膜炎中过度表达，并通过降解角膜胶原导致角膜浑浊、变薄甚至穿孔 29。MMPs的过度激活导致角膜基质中的胶原纤维、蛋白聚糖等主要成分被持续降解，使得角膜逐渐变薄。
此外，机械应力还会影响角膜细胞的行为和功能。机械应变可以导致角膜细胞形态改变、增殖受抑制并诱导细胞凋亡，同时下调角膜结构基因（如COL1A1、Lumican和Vimentin）的表达 28。例如，在角膜基质细胞中敲除TGF-β受体2（Tgfbr2）可导致角膜进行性变薄，并且在这些转基因小鼠上进行机械揉眼操作会诱发角膜水肿和积水 30。这表明角膜细胞对机械应力的响应异常是导致角膜病理改变的重要因素。
最终，这些病理改变——包括胶原交联破坏、MMPs过度激活导致ECM降解、角膜细胞功能障碍——共同导致了角膜的生物力学特性下降（软化）和进行性变薄，进而出现圆锥样突出，形成或加剧圆锥角膜。因此，避免揉眼是阻断这一恶性循环、延缓圆锥角膜进展的关键干预措施。
4. 揉眼对眼内压及青光眼的潜在影响
4.1 短期揉眼与眼内压波动
揉眼行为不仅对角膜结构造成直接机械损伤，还会对眼内压（IOP）产生显著且瞬时的影响。揉眼时，外部力量直接作用于眼球，对前房造成挤压，这类似于一个机械泵的作用，使房水短时间内难以正常引流。其生理机制主要包括以下几个方面：首先，直接的机械压迫导致眼球变形，挤压房水，使其在前房内压力升高；其次，揉眼可能暂时性地压迫小梁网，阻碍房水经由小梁网的正常排出通路，从而引起眼内压的急剧升高。
多项研究已证实揉眼可引起眼内压的显著波动。例如，一项对非人灵长类动物（NHP）的研究发现，揉眼可导致眼内压瞬时升高高达310 mmHg。即使是平均水平，揉眼也能使眼内压在3-4秒内平均升高80-150 mmHg。研究指出，用手背或手腕揉擦眼睛和眼眶所引起的眼压升高幅度最大，而非手指或指关节揉擦 31。这种短时间内的剧烈眼压升高，即使是暂时的，也可能对眼部结构造成潜在损伤。
对于某些特定患者群体，短期揉眼引起的眼内压波动风险尤为突出。例如，对于接受了微创青光眼手术（MIGS）的患者，如植入了XEN凝胶支架，术后揉眼行为可能导致支架移位，进而引发局部角膜损伤和眼内压异常。一项病例报告显示，一名接受XEN凝胶支架植入术的患者因术后常规揉眼，导致支架移位至前房内，并与角膜发生接触，造成角膜内皮细胞密度在短时间内显著下降2.1% 32。这提示，揉眼不仅可能影响MIGS手术效果，还可能带来严重的并发症。
此外，对于正在服用抗凝药物（如乙酰水杨酸）的患者，即使是轻微的揉眼也可能诱发微创伤，导致反复性前房积血和继发性青光眼。一项案例研究报告了一名长期服用乙酰水杨酸的患者，因强力揉眼导致反复性微量前房积血，并在两个月内发展为晚期青光眼，最终通过停止抗凝药物和手术才得以控制病情 33。这表明揉眼导致的眼压升高和机械损伤，在特定条件下，会增加眼内出血的风险，特别是对青光眼患者而言，这种短暂的眼压升高可能加剧视神经损伤。
因此，短期揉眼引起的眼内压波动是一个不容忽视的临床问题，尤其是在青光眼或相关手术后的患者中，更应强调避免揉眼，以预防潜在的并发症。
4.2 长期揉眼与青光眼进展
长期揉眼对眼内压的持续波动及其可能导致的病理生理改变，在青光眼的发生和进展中扮演了重要角色。虽然青光眼通常与持续性高眼压相关，但研究表明，眼压的慢性波动本身就可能对眼部结构造成损伤，特别是对小梁网细胞和视神经 34。
小梁网是房水排出系统的重要组成部分，负责调节眼内压。长期揉眼引起的眼内压波动，可能通过多种机制损害小梁网的功能。首先，反复的机械应力可能会对小梁网细胞造成物理损伤或功能障碍，影响其吞噬房水中碎屑的能力，进而降低房水引流效率。当房水引流受阻时，眼内压会进一步升高，形成恶性循环。
其次，慢性眼压波动还可能诱发小梁网细胞的氧化应激损伤 3435。氧化应激是细胞内活性氧（ROS）生成与抗氧化防御系统失衡的结果，过量的ROS会损害细胞膜、蛋白质和DNA，导致细胞功能紊乱甚至死亡。在青光眼发病机制中，氧化应激被认为是导致小梁网细胞损伤和房水引流功能退化的关键因素之一 3436。揉眼引起的眼压波动可能通过缺血-再灌注损伤机制加剧氧化应激。当眼压升高时，眼部血流可能暂时受阻，导致局部缺血；当眼压下降时，血流恢复，但在缺血后恢复血流（再灌注）的过程中，会产生大量的ROS，进一步损伤小梁网细胞 34。
视神经是青光眼病理损伤的最终靶点。眼压升高和波动，无论是否伴随氧化应激，都会对视神经造成机械性和生物化学性损伤 37383940。长期揉眼导致的慢性眼压波动，可以持续对视神经纤维施加压力，尤其是在视盘处，导致神经纤维受损和丢失，这在“正常眼压性青光眼”患者中尤为重要，因为即使在统计学正常的眼压范围内，视神经也可能因波动而受损 41。一项病例报告指出，一名有20年强力揉眼习惯的患者，表现为进行性双眼视神经病变，视盘出现病理性凹陷，并伴有视野缺损，停止揉眼后视力才得以稳定 41。这表明，长期揉眼是进行性视神经病变的一个潜在原因，甚至在眼压被认为是“正常”的情况下。
此外，研究表明，在慢性实验性青光眼模型中，眼内压升高会导致视神经头胶质细胞增殖和Jak-Stat通路的激活，这些改变与视神经损伤的进展密切相关 42。长期揉眼引起的眼压波动，可能通过类似的机制促进视神经胶质细胞的病理反应，从而加速青光眼的进展。
综上所述，长期揉眼通过持续的眼压波动、对小梁网细胞的氧化损伤以及直接或间接的视神经损害，可能显著影响青光眼的发生发展。对于有揉眼习惯的个体，特别是青光眼高风险人群或已确诊患者，避免揉眼是保护眼部健康、延缓疾病进展的重要措施。
5. 长期揉眼的其他眼部并发症
5.1 角膜内皮细胞功能损害
长期或频繁的揉眼行为对角膜内皮细胞会造成显著的损害，主要表现为角膜内皮细胞密度（Endothelial Cell Density, ECD）的降低，进而影响角膜的透明性和液体平衡功能。角膜内皮细胞位于角膜后表面，呈单层排列，具有重要的屏障和泵功能，维持角膜的脱水状态，是保持角膜透明的关键。内皮细胞一旦受损，再生能力极低，其损失是不可逆的。
多项临床研究数据证实了揉眼与ECD下降之间的关联。一项横断面研究对162名非糖尿病白内障患者的296只眼进行分析，结果发现，有揉眼习惯的个体平均ECD为2470 ± 275 cells/mm²，而无揉眼习惯的个体平均ECD为2611 ± 313 cells/mm²。这意味着揉眼者比非揉眼者的ECD平均降低了5.4%（P<0.000），即使在控制了年龄因素后，这种差异依然显著 43。另一项针对圆锥角膜患者的研究也观察到，角膜内皮细胞密度显著低于正常对照组（2412.2 ± 339.5 vs. 2845.6 ± 313.0 cells/mm²，P<0.001） 44。虽然该研究没有直接指出揉眼是ECD下降的唯一原因，但考虑到圆锥角膜与揉眼的高度关联性，可以推断揉眼在其中扮演了重要角色。
揉眼导致内皮细胞损害的机制可能包括：
- 直接机械应力损伤：揉眼时对眼球施加的压力和摩擦力可能直接作用于角膜内皮，导致内皮细胞的物理性损伤或脱落。特别是当眼球受到不均匀或反复的机械应力时，脆弱的内皮细胞更容易受损。
- 眼内压波动：如前所述，揉眼可引起眼内压的剧烈和短暂升高 43。这种反复的眼压波动可能对角膜内皮细胞产生剪切力和压应力，从而导致细胞损伤和功能障碍。
- 炎症介质的影响：揉眼诱发的眼部炎症反应，特别是促炎细胞因子的释放，可能间接损害角膜内皮细胞。炎症介质可能影响内皮细胞的代谢活动和屏障功能。
- 与眼内植入物的相互作用：在某些情况下，如植入眼内晶体（Phakic IOL）或青光眼引流装置（如XEN凝胶支架）后，揉眼可能导致这些植入物移位，进而与角膜内皮发生接触和摩擦。例如，一例XEN凝胶支架移位患者，因揉眼导致支架与角膜接触，在一个月内引起角膜内皮细胞密度下降2.1% 32。另一例白内障术后患者，因慢性瘙痒导致的过度揉眼，在植入虹膜固定型人工晶状体五年后出现单侧角膜基质水肿，七年后内皮细胞密度降至413 cells/mm²，最终导致角膜失代偿 45。甚至在具有角膜内皮失养症（如角膜滴状体）的患者中，揉眼也可能加速内皮失代偿的发生 46。
角膜内皮细胞密度的下降会削弱其维持角膜脱水状态的能力，导致角膜水肿，进而影响角膜透明性，使视力下降。因此，避免揉眼对于保护角膜内皮细胞功能，维持角膜健康和透明度至关重要。
5.2 结膜及眼表结构异常
长期揉眼除了对角膜内皮细胞造成损害外，还会导致结膜及眼表结构出现一系列异常，这些异常可能引发不适、影响视力甚至导致严重的并发症，尤其是在术后恢复期。
结膜下异物嵌顿是揉眼行为可能导致的直接后果之一。当患者感到眼部不适或异物感而进行揉眼时，尤其是在户外或灰尘较多的环境中，外源性物质，如植物性刺状异物，可能会在揉搓过程中被强行推入结膜下，甚至嵌入半月皱襞等隐蔽部位。一项病例报告描述了一位50岁女性，因剧烈揉眼后，一根带刺的植物性异物（长8毫米，直径4毫米）穿透结膜，嵌入半月皱襞下，导致持续性的眼部红肿和不适，最终需手术取出 47。此类异物嵌顿不仅会引起持续性炎症反应，若不及时处理，还可能引发感染或其他更严重的并发症。
泪膜稳定性破坏也是长期揉眼常见的影响。泪膜是覆盖在眼球表面的一层液体薄膜，由水层、黏蛋白层和脂质层组成，对维持眼表湿润、提供营养和清除异物至关重要。揉眼行为的机械性摩擦会直接干扰泪膜的正常结构，导致泪膜破裂时间（TBUT）缩短，进而引起眼表干燥症状，加重眼部不适。在过敏性结膜炎等眼表炎症患者中，揉眼与泪膜不稳定形成恶性循环，进一步损害眼表健康。
此外，揉眼对术后恢复的障碍影响尤其显著。眼科手术后，眼球组织处于脆弱的愈合阶段，任何形式的机械刺激都可能导致严重的并发症。例如，在白内障手术后，患者因术后眼部不适或轻微瘙痒而揉眼，可能导致虹膜脱垂等严重情况。一例65岁男性在白内障手术后一个月，因早期有瘙痒和揉眼史，导致虹膜脱垂出颞侧角膜清创切口，造成显著的虹膜组织缺失，引起严重的眩光和光晕，最终不得不进行复杂的修复手术 48。即使是轻微的揉眼也可能导致术后伤口裂开、人工晶体移位、角膜水肿加剧甚至感染，这些并发症都可能严重影响手术效果和患者视力预后。在翼状胬肉患者中，揉眼或结膜下异物刺激同样可能导致结膜下出血，电子显微镜观察发现，此类出血是由于毛细血管内皮细胞和基底膜中断，导致血细胞渗漏所致 49。
因此，避免揉眼对于维护结膜和眼表结构的完整性、保持泪膜稳定以及确保眼科手术后的顺利恢复至关重要。临床医生应向患者强调揉眼的潜在危害，并积极处理可能导致揉眼的基础眼部疾病。
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参考文献
1Epithelial responses to rubbing-related mechanical forces.PubMed
Charles W McMonnies, Ahmed Alharbi, Gavin C Boneham
Cornea. 2010 Nov;29(11):1223-31. doi: 10.1097/ICO.0b013e3181d3d660.
PURPOSE: To examine for epithelial thickness changes in response to compressive and shear forces associated with eye rubbing. METHODS: The Holden-Payor optical pachometer was used to measure total and stromal-endothelial thickness, at central (right eye) and midperipheral (left eye) locations, for 12 subjects with normal corneas. Epithelial thickness was determined by subtraction. Baseline measurements were compared with measurements recorded immediately after 15 seconds of circular pattern rubbing over the cornea, using an index finger pad, and light to moderate force. Four subjects in each of 3 groups with mean ages of 19.5, 45.3, and 70.2 years were assessed. Measurement continued at 15-minute intervals until baseline thickness was restored. RESULTS: An 18.4% reduction in epithelial thickness was recorded immediately after rubbing for central right eye and midperipheral left eye assessments. Both findings were statistically significant (P < 0.05). Recovery to baseline thickness occurred between 15 and 30 minutes centrally and between 30 and 45 minutes midperipherally. CONCLUSION: These results indicate a statistically significant mechanical trauma to the epithelium after 15 seconds of light to moderate rubbing. With reference to the rheological properties of the cytoskeleton, an attempt to explain how the epithelium could lose and recover thickness has been made. Apart from cell flattening, displacement from the rubbed area of intercellular water, cytoplasm from ruptured cells, chains of wing cells, and mucin are suggested as possible thinning mechanisms. Extraneous eye rubbing may adversely alter the results obtained with pachymetry, videokeratography, wavefront aberrometry, refraction, and results obtained with orthokeratology contact lenses.
2Keratocyte apoptosis associated with keratoconus.PubMed
W J Kim, Y S Rabinowitz, D M Meisler, et al.
Exp Eye Res. 1999 Nov;69(5):475-81. doi: 10.1006/exer.1999.0719.
Keratoconus is an ectatic corneal dystrophy associated with stromal thinning and disruption of Bowman's layer. The purpose of this study was to explore a possible association between keratocyte apoptosis and keratoconus. Keratocyte apoptosis was evaluated in corneas of patients with keratoconus, corneas of patients with stromal dystrophies, and normal donor corneas using the transferase-mediated dUTP-digoxigenin nick and labeling (TUNEL) assay. Keratocyte apoptosis was also studied in keratoconus and normal corneas using transmission electron microscopy. TUNEL-stained keratocytes were detected in 60% of corneas with keratoconus, but only 35% of corneas with stromal dystrophies (P =0.03). The number of TUNEL-positive keratocytes detected in the keratoconus, stromal dystrophy, and normal corneas was 7+/-1 (mean+/-standard error, range 0-20), 2+/-0. 8 (range 0-9), and 0+/-0 (range 0-0) TUNEL-positive cells per section, respectively. The differences between the keratoconus and the stromal dystrophy (P =0.0097) or the normal cornea (P =0.01) groups were statistically significant. The difference between the stromal dystrophy and normal cornea groups was not statistically significant (P =0.45). The stromal dystrophy group was included to account for surgery-associated keratocyte apoptosis. No TUNEL-stained keratocytes were detected in normal corneas. Cell morphologic changes consistent with apoptosis were detected by transmission electron microscopy (TEM) in keratocytes of keratoconus corneas, but not in keratocytes in normal corneas. Chronic keratocyte apoptosis associated with ongoing epithelial injury may link risk factors associated with keratoconus such as chronic eye rubbing, contact lens wear, or atopic eye disease. Similarly, increases that have been detected in several different degradative enzymes in keratoconus corneas could be associated with chronic keratocyte apoptosis and less than perfect control of release of intracellular contents.
3Mechanical Strain of Corneal Epithelium Influences the Expression of Genes Implicated in Keratoconus.PubMed
Loren Moon, Pritpal Kaur, Jiangxia Wang, et al.
Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):52. doi: 10.1167/iovs.66.1.52.
PURPOSE: Although mechanical injury to the cornea (e.g. chronic eye rubbing) is a known risk factor for keratoconus progression, how it contributes to loss of corneal integrity is not known. Here, we set out to determine how eye rubbing can influence keratoconus progression by exploring the expression of known disease markers in mechanically stressed corneal epithelial cells. METHODS: To explore the effects of mechanical stress on the expression of genes implicated in keratoconus (e.g. WNT10A, COL12A1, and TGFB1), we measured their expression using an in vitro model that simulates eye rubbing by cyclic stretching of an immortalized human corneal epithelial cell line (hTCEpi) for 16 hours. We further examined the influence of WNT10A expression in hTCEpi cells using loss-of-function approaches. RESULTS: Mechanical strain led to a marked reduction in WNT10A mRNA and protein expression, as well as decreased collagen XII mRNA and protein expression, in hTCEpi cells. Reduced expression of WNT10A protein in WNT10A knockdown cells resulted in reduced protein expression of collagens I and XII, and reduced mRNA expression of MMP9 and TGFB1. Conversely, primary keratocytes treated with recombinant WNT10A protein increased TGFB1 mRNA expression. CONCLUSIONS: We provide a molecular explanation for how mechanical strain results in reduced expression of WNT10A in the corneal epithelium, which, in turn, leads to depletion of collagen type I and XII, and TGFβ1 expression. These results provide a molecular link among mechanical strain, WNT10A expression, and the biomechanical failure of the keratoconus cornea.
4Occult Perforating Corneal Injury from Mechanical Pencil Graphite.PubMed
David A Paine, Paul B Pruett, J Bradley Randleman
Ophthalmic Surg Lasers Imaging. 2010 Apr 2:1-3. doi: 10.3928/15428877-20100325-11.
An 11-year-old boy was struck in the left eye with a mechanical pencil in a projectile manner. Initial examination under the operating microscope revealed a presumed partial-thickness corneal injury with a retained 8-mm long segment of graphite lead. After removal of the graphite segment, a full-thickness hole in the cornea was revealed under the lead shaft. The proposed mechanism of injury and unique presentation was initial full-thickness penetration followed by lead shaft retraction (likely due to eye rubbing) and then corneal stromal reentry with stromal lamellar dissection and fixation. Prompt removal of the foreign body, corneal laceration repair, and early cataract extraction resulted in postoperative 20/40 uncorrected visual acuity. Mechanical lead pencil injuries represent a unique mechanism of penetrating trauma.
5Keratoconus.PubMed
Rohan Bir Singh, Shizuka Koh, Namrata Sharma, et al.
Nat Rev Dis Primers. 2024 Oct 24;10(1):81. doi: 10.1038/s41572-024-00565-3.
Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed.
6Biomechanics of keratoconus: Two numerical studies.PubMed
Nicolas Falgayrettes, Etienne Patoor, Franck Cleymand, et al.
PLoS One. 2023 Feb 2;18(2):e0278455. doi: 10.1371/journal.pone.0278455. eCollection 2023.
BACKGROUND: The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies. METHODS: A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress. RESULTS: Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman's membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected. DISCUSSION: These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy.
7The Effects of Eye Rubbing on Corneal Topography and Biomechanics in Children With Allergic Conjunctivitis.PubMed
Xiaoguang Niu, Aijiao Qin, Wenbo Zhang, et al.
Transl Vis Sci Technol. 2025 Oct 1;14(10):18. doi: 10.1167/tvst.14.10.18.
PURPOSE: To characterize corneal topographic and biomechanical alterations in children with allergic conjunctivitis and evaluate their association with eye rubbing frequency. METHODS: This cross-sectional study enrolled children aged eight to fourteen years with diagnosed perennial/seasonal allergic conjunctivitis treated at our institution (January 2023-March 2025). All participants underwent routine ophthalmologic examinations, corneal topography, and visualized corneal biomechanics assessments. The results were compared with age- and sex-matched healthy controls. Eye rubbing frequency was documented, and correlation analyses and mediation effect analysis were conducted between eye rubbing frequency and altered corneal topographic and biomechanical parameters. RESULTS: No significant differences were found between the allergic conjunctivitis group and the control group regarding age, sex, or spherical equivalent. Among corneal topographic parameters, front elevation at the thinnest point (Fe) and front difference deviation (Df) were significantly higher in the allergic group compared to controls. In terms of corneal biomechanical parameters, the first applanation length (A1L) and stiffness parameter at first applanation (SP-A1) were significantly lower in the allergic group. Fe and Df were positively correlated with eye rubbing frequency and fully mediated the effect of eye rubbing on the Tomographic and Biomechanical Index (TBI). A1L and SP-A1 were not correlated with eye rubbing frequency and did not mediate its effect of eye rubbing on TBI. CONCLUSIONS: Children with allergic conjunctivitis exhibit increased anterior corneal surface height and front difference deviation. These abnormalities are associated with the frequency of eye rubbing, which influences the TBI via changes in Fe and Df. TRANSLATIONAL RELEVANCE: Eye rubbing in children with allergic conjunctivitis causes specific corneal topographic changes. Detecting these changes early allows for timely intervention to reduce rubbing and may help prevent the risk of progressive corneal deformation.
8The Impact of Repetitive and Prolonged Eye Rubbing on Corneal Biomechanics.PubMed
Emilio A Torres-Netto, Hormoz Abdshahzadeh, Reyhaneh Abrishamchi, et al.
J Refract Surg. 2022 Sep;38(9):610-616. doi: 10.3928/1081597X-20220715-03. Epub 2022 Sep 1.
PURPOSE: To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system. METHODS: The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips. RESULTS: The elastic modulus at the range of 1% and 5% of strain was 1.219 ± 0.284 and 1.218 ± 0.304 N/mm in the eye rubbing group and the no-rub control group, respectively. Corneal stiffness was similar in both groups ( = .984). CONCLUSIONS: The threshold to induce biomechanical changes (purely by eye rubbing) must be higher than 10,500 rubbing movements, suggesting that occasional eye rubbing may not affect corneal biomechanics in normal eyes, and likely only triggers keratoconus progression in predisposed corneas. Further in vivo studies assessing the impact eye rubbing has on inflammatory activity and the biomechanical properties of weakened corneas is warranted. .
9Keratoconus prognosis study for patients with corneal external mechanical stress mode.PubMed
Toufik Bettahar, Chemseddine Rahmoune, Djamel Benazzouz
Int Ophthalmol. 2020 Jul;40(7):1673-1686. doi: 10.1007/s10792-020-01335-2. Epub 2020 Mar 26.
PURPOSE: To demonstrate the correlation between excessive eye rubbing and corneal degeneration for Keratoconus patients. MATERIALS AND METHODS: Keratoconus (KC) patients who regularly rub their eyes had shown a rapid degeneration rate of their affected corneas. This observation is experimentally and numerical discussed and developed based on clinical data of 8 of KC Patients with a mean age of 26.5 ± 9.4 years old, and four healthy individuals with a mean age of 24.33 ± 5 years old at the baseline. Corneal topography was used to measure both central corneal thickness (CCT) and its total refractive power. The registered data had been exploited to assess the progression of the disease, and the final results were embedded in a finite element model of human corneas to simulate their response to eye rubbing at different stages of the pathology. Corneal lifetime prognosis using multi-layer perceptron was then established to estimate the number of eye rubbing cycles for each stage of KC. RESULTS: The survey of KC patients who declared stopping eye rubbing had shown a decrease in CCT loss rate, followed by a durable stability. Mechanical stresses numerical simulations had shown different corneal behaviours in term of shape deformity, apical raise and corneal applanation between healthy and KC stages models. Apical rise ranged from 0.122 to 0.389 mm for an applied intraocular pressure that equals to 15 mmHg. A normal stress of 5 kPa provoked a corneal applanation that ranged from 0.27 mm in healthy cases to 1.173 mm in severe stages of the disease. The application of 2.5 kPa biaxial stress had resulted normal and tangential applanations that successively ranged from 0.152 and 0.173 mm in healthy corneas to 0.446 mm and 0.458 mm in severe KC stages. An adopted prognosis algorithm was able to predict the current stage of the disease and to estimate the remaining number of eye rubbing cycles before failure. CONCLUSION: Eye rubbing was proven to be a considerable contributing factor in KC patient's corneal degeneration. The progression of this pathology could be decreased or halted by stopping eye rubbing at early stages.
10Multimodal diagnostics for keratoconus and ectatic corneal diseases: a paradigm shift.PubMed
Renato Ambrósio, Marcella Q Salomão, Lorena Barros, et al.
Eye Vis (Lond). 2023 Nov 3;10(1):45. doi: 10.1186/s40662-023-00363-0.
Different diagnostic approaches for ectatic corneal diseases (ECD) include screening, diagnosis confirmation, classification of the ECD type, severity staging, prognostic evaluation, and clinical follow-up. The comprehensive assessment must start with a directed clinical history. However, multimodal imaging tools, including Placido-disk topography, Scheimpflug three-dimensional (3D) tomography, corneal biomechanical evaluations, and layered (or segmental) tomography with epithelial thickness by optical coherence tomography (OCT), or digital very high-frequency ultrasound (dVHF-US) serve as fundamental complementary exams for measuring different characteristics of the cornea. Also, ocular wavefront analysis, axial length measurements, corneal specular or confocal microscopy, and genetic or molecular biology tests are relevant for clinical decisions. Artificial intelligence enhances interpretation and enables combining such a plethora of data, boosting accuracy and facilitating clinical decisions. The applications of diagnostic information for individualized treatments became relevant concerning the therapeutic refractive procedures that emerged as alternatives to keratoplasty. The first paradigm shift concerns the surgical management of patients with ECD with different techniques, such as crosslinking and intrastromal corneal ring segments. A second paradigm shift involved the quest for identifying patients at higher risk of progressive iatrogenic ectasia after elective refractive corrections on the cornea. Beyond augmenting the sensitivity to detect very mild (subclinical or fruste) forms of ECD, ectasia risk assessment evolved to characterize the inherent susceptibility for ectasia development and progression. Furthermore, ectasia risk is also related to environmental factors, including eye rubbing and the relational impact of the surgical procedure on the cornea.
11Determination of efficacy of repeated CXL and probable risk factors in patients with progressive keratoconus.PubMed
Hossein Jamali, Milad Bagheri, Mohammad Reza Khalili
Int Ophthalmol. 2023 Sep;43(9):3157-3164. doi: 10.1007/s10792-023-02715-0. Epub 2023 May 17.
PURPOSE: To evaluate the efficacy of Repeated CXL (Re-CXL) and determine probable risk factors that lead to Re-CXL in patients with progressive keratoconus. METHOD: In this retrospective study, the medical records of patients who had been re-operated in our center between 2014 to 2020 due to progressive keratoconus were evaluated; seven eyes of seven patients had undergone Re-CXL procedure. Pre- and post-treatment variables were recorded and analyzed using IBM SPSS Statistics software. RESULTS: The mean interval between the 1st and 2nd CXL was 49.71 months (range 12-72 months). Out of 7 patients for whom Re-CXL was considered necessary, eye rubbing was detected in 6 patients. Six patients were very young with a mean age of 13 years at primary CXL and 16.83 years at Re-CXL. Visual acuity and astigmatism did not change significantly after the Re-CXL procedure (p-values = 0.18, 0.91, respectively). When measurements of these indices prior to Re-CXL and post Re-CXL were compared, K1 (p-value = 0.01), K2 (p-value = 0.01), Kmean (p-value = 0.01), and Kmax (p-value = 0.008) changed significantly. As to pachymetry (p-value = 0.46), it did not change significantly. Kmax value regressed in all eyes after Re-CXL. CONCLUSION: Re-CXL procedure was effective in halting the progression of disease. As to the risk factors, eye rubbed-related mechanism like eye rubbing and VKC, lower age, and pre-operative Kmax value > 58 D are the risk factors of Re-CXL procedure.
12Mechanoreceptor Piezo1 channel-mediated interleukin expression in conjunctival epithelial cells: Linking mechanical stress to ocular inflammation.PubMed
Seiya Fukuoka, Naoki Adachi, Erika Ouchi, et al.
Ocul Surf. 2025 Apr;36:56-68. doi: 10.1016/j.jtos.2025.01.001. Epub 2025 Jan 6.
PURPOSE: Mechanical stress on the ocular surface, such as from eye-rubbing, has been reported to lead to inflammation and various ocular conditions. We hypothesized that the mechanosensitive Piezo1 channel in the conjunctival epithelium contributes to the inflammatory response at the ocular surface after receiving mechanical stimuli. METHODS: Human conjunctival epithelial cells (HConjECs) were treated with Yoda1, a Piezo1-specific agonist, and various allergens to measure cytokine expression levels using qRT-PCR. Piezo1 activation-induced intracellular signaling pathways were also investigated by Western blot. Mechanical stretching experiments were conducted to simulate Piezo1 activation in HConjECs. Specificity of Piezo1 was confirmed by PIEZO1 knockdown and GsMTx4. In in vivo studies, using immunohistochemistry, rats were administered Yoda1 eye drops to examine the inflammatory response in the conjunctiva and Piezo1-induced signaling activation. RESULTS: HConjECs expressed functional Piezo1 channel which was the dominant mechanoreceptor among putative channels and whose activation significantly increased IL-6 and IL-8 expression through the p38 MAPK-CREB pathway. Piezo1-induced [Ca] elevation was crucial for the production of IL-6. The Yoda1-induced inflammatory responses were blocked by PIEZO1 knockdown. Mechanical stretching mimicked these effects, which were suppressed by GsMTx4. In vivo, Yoda1 administration led to increased phospho-p38 MAPK, phospho-CREB, and IL-6 in the rat conjunctival epithelium, with significant neutrophil infiltration. CONCLUSION: Mechanical stress-induced Piezo1 channel activation in conjunctival epithelial cells can cause ocular inflammation by upregulating pro-inflammatory cytokines via the p38 MAPK-CREB pathway and promoting neutrophil infiltration. These findings suggest that mechanical stimuli on ocular surface tissues are significant risk factors for ocular inflammation.
13Vernal keratoconjunctivitis and keratoconus.PubMed
Denise Wajnsztajn, Abraham Solomon
Curr Opin Allergy Clin Immunol. 2021 Oct 1;21(5):507-514. doi: 10.1097/ACI.0000000000000765.
PURPOSE OF REVIEW: Vernal keratoconjunctivitis (VKC) is a severe allergic inflammatory disease affecting the conjunctiva in children and young adults. Keratoconus (KC) is a progressive corneal disease characterized by thinning of the corneal stroma, increased and asymmetric corneal curvature, with a potential for significant visual deterioration and is one of the most common corneal complications of VKC. We aimed to review the association of these two diseases, with focus on the mechanisms, prevalence, natural history and treatment strategies of KC associated with VKC. RECENT FINDINGS: KC is a common complication of VKC. KC prevalence can be as high as 26.8% among VKC patients, whereas abnormal corneal topography may appear in up to 71% of them. It is more severe and progresses faster in the setting of VKC (P < 0.05), with remarkable visual deterioration and with an increased need for keratoplasty. Crosslinking treatment and corneal transplantation appear to be as effective for KC patients with VKC as compared to the patients without VKC. However, postoperative complications are higher in patients with VKC and demand close monitoring, tight control of local inflammation and prompt awareness with consequent restrain of eye rubbing. SUMMARY: Patients with VKC should be closely monitored for KC. Prompt recognition of VKC and KC allows tight control of KC pathogenesis mechanisms, timely management of KC progression and preservation of vision and quality of life of young patients.
14Corneal biomechanics in patients with allergic conjunctivitis.PubMed
Wan Haslina Wan Abdul Halim, Mohd Ihsan Jamaludin, Teck Chee Cheng
Indian J Ophthalmol. 2024 Nov 1;72(Suppl 5):S728-S733. doi: 10.4103/IJO.IJO_654_24. Epub 2024 Sep 19.
Allergic conjunctivitis (AC) comprises a group of conditions triggered by environmental allergens, substantially diminishing the quality of life, particularly among children and adolescents. The mechanical impact of eye rubbing in patients with AC is known to induce biomechanical alterations in the cornea. Modern instruments enable the detection and quantification of these corneal biomechanical changes. The ocular response analyzer and CorVis ST have become standard tools for assessing corneal biomechanical properties. We conducted a review of studies that have investigated corneal biomechanics in patients with AC using both devices to elucidate the association between corneal biomechanical changes and early ectasia development. Our analysis highlights significant findings regarding the tomographic biomechanical index parameter in corneal biomechanics among patients with AC. These findings underscore the importance of ocular screening for all patients to promptly detect subclinical keratoconus changes, thereby improving disease management and outcomes.
15Corneal biomechanical changes in allergic conjunctivitis.PubMed
Qian Wang, Yuqing Deng, Saiqun Li, et al.
Eye Vis (Lond). 2021 May 3;8(1):17. doi: 10.1186/s40662-021-00241-7.
BACKGROUND: To explore corneal biomechanical changes, identify related factors and determine early indicators of keratoconus (KC) development risk in allergic conjunctivitis (AC) patients. METHODS: A total of 50 patients, including 20 eyes without AC and 30 eyes with AC were enrolled in this study. All patients underwent a complete ocular examination, including evaluations of clinical manifestations of AC, corneal tomography and densitometry by Pentacam, corneal biomechanics by Corvis ST, and corneal and epithelial thickness mapping by RTvue optical coherence tomography (OCT). RESULTS: The index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), index of height decentration (IHD) and Belin/Ambrosio enhanced ectasia total deviation index (BAD-D) were significantly higher in the AC group than in the non-allergic conjunctivitis (NAC) group (P < 0.05). The tomography and biomechanical index (TBI) was also significantly higher in the AC group (P = 0.04). The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group (P < 0.05). The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group (P < 0.001). The ISV, IVA, KI, IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients (P < 0.05). The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores (P < 0.05). CONCLUSIONS: AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements, and the TBI could be used as an indicator of KC development risk in AC patients. TRIAL REGISTRATION: Corneal Biomechanical Changes of Allergic Conjunctivitis, NCT04299399 . Registered March 3, 2020 - Retrospectively registered.
16Non-genetic risk factors for keratoconus.PubMed
Minji Song, Qing Yi Fang, Ishith Seth, et al.
Clin Exp Optom. 2023 May;106(4):362-372. doi: 10.1080/08164622.2022.2062222. Epub 2022 May 3.
Keratoconus is a complex and multifactorial disease and its exact aetiology remains unknown. This current study examined the important environmental risk factors and their association with keratoconus. This study was registered in the PROSPERO International Prospective Register of systematic reviews under registration number CRD42021256792 in 2021. Scopus, Web of Science, PubMed, and Cochrane CENTRAL databases were searched for all relevant articles published from 1 January 1900 to 31 July 2021. National Institutes of Health Quality Assessment Tool was used to assess the methodological quality of the studies. The assessment for statistical heterogeneity was assessed using the Z-statistics on RevMan v5.4. P-value of <0.05 was considered as statistically significant and I < 25% as homogenous. Thirty studies were included in this meta-analysis. Pooled odds ratio was calculated with 95% CI. The pooled odds ratio (OR) of eye rubbing, atopy, asthma, and eczema was 3.64 (95% CI, 2.02, 6.57), 1.90 (95% CI, 1.22, 2.94), 1.36 (95% CI, 1.15, 1.61) and 1.90 (95% CI, 1.22, 2.94), respectively. The OR for diabetes was 0.86 (95% CI 0.73, 1.02), and use of sunglasses, contact lens, allergic conjunctivitis, side sleep position and prone sleep position was 0.40 (95% CI, 0.16, 0.99), 1.68 (0.70, 4.00), 2.24 (95% CI, 0.68, 7.36), 3.81 (95% CI, 0.31, 46.23), 12.76 (95% CI, 0.27, 598.58), respectively. Twenty studies were considered to be of high quality, nine to be moderate and one to be low. Environmental risk factors have been identified to play a role in the susceptibility of keratoconus. However, further large-scale longitudinal studies are needed to understand the mechanisms between environmental risk factors and keratoconus.
17Keratoconus epidemiology: A review.PubMed
José A P Gomes, Pablo F Rodrigues, Luiz L Lamazales
Saudi J Ophthalmol. 2022 Jul 11;36(1):3-6. doi: 10.4103/sjopt.sjopt_204_21. eCollection 2022 Jan-Mar.
Keratoconus is an ectatic corneal disease that affects both men and women, usually at a young age. Risk factors such as eye rubbing, environmental and genetic factors contribute to its pathogenesis. Keratoconus presents a variable prevalence, being as high as 5% of the population in the Middle East. In this review, an English-language search for keratoconus epidemiology was undertaken using the PubMed database. We present and discuss the findings of the most relevant epidemiological studies on keratoconus and describe its characteristics and risk factors, correlating them with its pathogenesis.
18What causes keratoconus?PubMed
Joel Sugar, Marian S Macsai
Cornea. 2012 Jun;31(6):716-9. doi: 10.1097/ICO.0b013e31823f8c72.
PURPOSE: The etiology of keratoconus has been the subject of numerous studies. Here, we review the body of literature that attempts to determine what causes keratoconus. METHODS: A review of the published literature was performed to evaluate the possible causes of keratoconus and how the different etiologies may play a role in the development of this disease. RESULTS: Peer-reviewed published papers and recent abstracts concerning the different etiologies of keratoconus were reviewed and discussed. Biochemical, genetic, and environmental factors are reviewed. The role of eye rubbing and atopic disease are explored. CONCLUSIONS: We agree with the hypothesis that there is a genetic predisposition that requires a "second hit" or environmental event to elicit progressive disease in keratoconus. Eye rubbing may serve as the "second hit" in some predisposed individuals. Inflammatory mediator studies question if keratoconus is really a noninflammatory thinning disorder of the cornea.
19Keratoconus: An updated review.PubMed
Jacinto Santodomingo-Rubido, Gonzalo Carracedo, Asaki Suzaki, et al.
Cont Lens Anterior Eye. 2022 Jun;45(3):101559. doi: 10.1016/j.clae.2021.101559. Epub 2022 Jan 4.
Keratoconus is a bilateral and asymmetric disease which results in progressive thinning and steeping of the cornea leading to irregular astigmatism and decreased visual acuity. Traditionally, the condition has been described as a noninflammatory disease; however, more recently it has been associated with ocular inflammation. Keratoconus normally develops in the second and third decades of life and progresses until the fourth decade. The condition affects all ethnicities and both sexes. The prevalence and incidence rates of keratoconus have been estimated to be between 0.2 and 4,790 per 100,000 persons and 1.5 and 25 cases per 100,000 persons/year, respectively, with highest rates typically occurring in 20- to 30-year-olds and Middle Eastern and Asian ethnicities. Progressive stromal thinning, rupture of the anterior limiting membrane, and subsequent ectasia of the central/paracentral cornea are the most commonly observed histopathological findings. A family history of keratoconus, eye rubbing, eczema, asthma, and allergy are risk factors for developing keratoconus. Detecting keratoconus in its earliest stages remains a challenge. Corneal topography is the primary diagnostic tool for keratoconus detection. In incipient cases, however, the use of a single parameter to diagnose keratoconus is insufficient, and in addition to corneal topography, corneal pachymetry and higher order aberration data are now commonly used. Keratoconus severity and progression may be classified based on morphological features and disease evolution, ocular signs, and index-based systems. Keratoconus treatment varies depending on disease severity and progression. Mild cases are typically treated with spectacles, moderate cases with contact lenses, while severe cases that cannot be managed with scleral contact lenses may require corneal surgery. Mild to moderate cases of progressive keratoconus may also be treated surgically, most commonly with corneal cross-linking. This article provides an updated review on the definition, epidemiology, histopathology, aetiology and pathogenesis, clinical features, detection, classification, and management and treatment strategies for keratoconus.
20The correlation between keratoconus and eye rubbing: a review.PubMed
Hatim Najmi, Yara Mobarki, Khalid Mania, et al.
Int J Ophthalmol. 2019 Nov 18;12(11):1775-1781. doi: 10.18240/ijo.2019.11.17. eCollection 2019.
Keratoconus is a non-inflammatory disorder which is gradual in development; corneal thinning and ectatic protrusion characterizes it. Keratoconus prevalence varies between different regions depending on several factors that affecting its prevalence. There are risk factors for developing keratoconus such as demographic and environmental factors. It was suggested that eye rubbing was associated with the development of keratoconus. The main aim of this review was to summarize the literature data about keratoconus and to identify the role of eye-rubbing in the aetiology of the disease. A number of 24 articles was reviewed through the PubMed, Google Scholar and Research Gates. There are many keywords used such as keratoconus, aetiology of keratoconus, eye rubbing, keratoconus prevalence, keratoconus and eye rubbing correlation. We concluded that eye rubbing causes the thinning of keratocyte, and the degree of effect of eye rubbing depends on the period and force of performing eye rubbing. It is recommended to avoid eye rubbing to prevent keratoconus, this can be achieved by avoiding itching and treating dryness of the eye and avoiding wearing eye lenses.
21The Prevalence and Risk Factors for Keratoconus: A Systematic Review and Meta-Analysis.PubMed
Hassan Hashemi, Samira Heydarian, Elham Hooshmand, et al.
Cornea. 2020 Feb;39(2):263-270. doi: 10.1097/ICO.0000000000002150.
PURPOSE: This study was conducted to determine the prevalence and risk factors for keratoconus worldwide. METHODS: In this meta-analysis, using a structured search strategy from 2 sources, 4 electronic databases (PubMed, Web of Science, Google Scholar, and Scopus) and the reference lists of the selected articles were searched from inception to June 2018 with no restrictions and filters. The outcome of the study was the prevalence of keratoconus and its risk factors, including eye rubbing, family history of keratoconus, atopy, allergy, asthma, eczema, diabetes type I and type II, and sex. RESULTS: In this study, 3996 articles were retrieved, of which 29 were analyzed. These 29 articles included 7,158,241 participants from 15 countries. The prevalence of keratoconus in the whole population was 1.38 per 1000 population [95% confidence interval (CI): 1.14-1.62 per 1000]. The prevalence of keratoconus was 20.6 per 1000 (95% CI: 11.68-28.44 per 1000) in men and 18.33 per 1000 (95% CI: 8.66-28.00 per 1000) in women in studies reporting sex. The odds ratio of eye rubbing, family history of keratoconus, allergy, asthma, and eczema was 3.09 (95% CI: 2.17-4.00), 6.42 (95% CI: 2.59-10.24), 1.42 (95% CI: 1.06-1.79), 1.94 (95% CI: 1.30-2.58), and 2.95 (95% CI: 1.30-4.59), respectively. CONCLUSIONS: The results of this study, as the most comprehensive meta-analysis of keratoconus prevalence and risk factors, showed that keratoconus had a low prevalence in the world and eye rubbing, family history of keratoconus, allergy, asthma, and eczema were the most important risk factors for keratoconus according to the available evidence.
22Eye rubbing in the aetiology of keratoconus: a systematic review and meta-analysis.PubMed
Srujana Sahebjada, Haitham H Al-Mahrouqi, Sophia Moshegov, et al.
Graefes Arch Clin Exp Ophthalmol. 2021 Aug;259(8):2057-2067. doi: 10.1007/s00417-021-05081-8. Epub 2021 Jan 23.
PURPOSE: Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis. METHODS: Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (I) tests. A p value of < 0.05 was considered as statistically significant and I < 30% as homogenous. Begg funnel plot was used to interpret the asymmetry or small study effects. RESULTS: Eight case-control studies were included in this systematic review. Two studies assessed eye rubbing without odds ratios and thus were excluded. The pooled odds ratios for the six remaining studies included in the meta-analysis was 6.46 (95% CI 4.12-10.1). The study results were heterogenous (I = 71.69 [95% CI 35.14-87.88]). All the studies scored moderate quality methodology on the Newcastle-Ottawa scale. Begg funnel plot showed asymmetry supporting heterogeneity. CONCLUSION: Eye rubbing showed consistent association with keratoconus. However, the current evidence is limited to only a small number of case-control studies which present as heterogeneous and of sub-optimal methodological quality. Additionally, the cause-effect temporal relationship cannot be determined. Further studies are needed to address this intricate relationship of eye rubbing and its induction, ongoing progression, and severity of keratoconus.
23Relevance of IgE, allergy and eye rubbing in the pathogenesis and management of Keratoconus.PubMed
Prerna Ahuja, Zelda Dadachanji, Rohit Shetty, et al.
Indian J Ophthalmol. 2020 Oct;68(10):2067-2074. doi: 10.4103/ijo.IJO_1191_19.
Keratoconus (KC) is an ectatic disease of the cornea characterized by localized thinning and protrusion causing irregular astigmatism, which can lead to significant visual impairment. KC has often been associated with allergy and/or atopy, which are immune-mediated inflammatory reactions primarily driven by IgE. A higher proportion of KC patients were reported to have history or suffer from systemic and/or ocular allergy with elevated allergen-specific IgE and/or total serum IgE. Eye rubbing, one of the risk factors for worsening of the disease and developing related complications in KC, is associated with IgE driven conditions. The current review enumerates and contextualizes the evidence related to IgE in mediating KC pathogenesis, including aberrant extra-cellular matrix remodeling. This review also discusses clinical strategies directed at modulating IgE-mediated responses in the management of KC, and the emerging academic and plausible clinical relevance of assessing serum and tear IgE (allergen-specific and total) status in improving the understanding of disease pathobiology, treatment planning, and prognosis.
24Psychiatric Comorbidities Associated With Keratoconus.PubMed
Margarita Safir, Idan Hecht, Dan Heller, et al.
JAMA Ophthalmol. 2023 Dec 1;141(12):1145-1150. doi: 10.1001/jamaophthalmol.2023.5176.
IMPORTANCE: Evaluating risk factors for keratoconus, often associated with recurrent eye rubbing, could generate hypotheses to be tested in future interventional trials. OBJECTIVE: To assess the risk for keratoconus associated with psychiatric comorbidities in adolescents and adults. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study included medical records of Israeli adolescents and adults in military service from January 2011 through December 2021. MAIN OUTCOMES AND MEASURES: The prevalence of anxiety, obsessive compulsive disorder (OCD), autism, and attention-deficit/hyperactivity disorder (ADHD) was evaluated in individuals with and without keratoconus. The association between keratoconus and psychiatric comorbidities was tested using univariate and multivariant analyses. RESULTS: Overall, 940 763 adolescents and adults were included. Mean (SD) age was 17.56 (1.47) years, and 59.3% were male. Keratoconus was documented in 1533 individuals, with a prevalence of 0.16%. Patients with keratoconus were more likely to be diagnosed with ADHD compared with the general population (odds ratio [OR], 1.58; 95% CI, 1.38-1.81; P < .001). After adjusting for age, sex, intellectual status, height, and weight, the results remained unchanged (hazard ratio, 1.46; 95% CI, 1.27-1.67; P < .001). Stratification according to age showed an association between keratoconus and ADHD for males (OR, 1.62; 95% CI, 1.39-1.90; P < .001) but not for females (OR, 1.29; 95% CI, 0.96-1.74; P = .09). CONCLUSIONS AND RELEVANCE: In a large cohort of adolescents and adults, ADHD was associated with a diagnosis of keratoconus in male patients, even after adjusting for possible confounders. Although a causative effect could not be ascribed, these findings support further investigation into the potential value of education regarding eye rubbing in this population.
25An Ex Vivo Model to Study Early Changes in Keratoconus.PubMed
Pritpal Kaur, Loren Moon, Deepti Sharma, et al.
Cornea. 2025 Nov 1;44(11):1410-1416. doi: 10.1097/ICO.0000000000003903. Epub 2025 Jun 3.
PURPOSE: To develop an ex vivo model for keratoconus that simulates eye rubbing, a hallmark characteristic of patients with this disease. METHODS: Uniaxial stretch (3% strain, 6 h) was applied to human stromal caps placed in stretch chambers, followed by hematoxylin and eosin staining and evaluation of Bowman layer (BL) breaks in stretched corneas compared with unstretched controls. The impact of mechanical strain on corneal epithelium was also assessed by applying similar cyclical strain to mouse eyes, and changes in basal epithelium morphology were examined using F-actin immunostaining. In addition, Wnt10a and Col12a1 mRNA levels were analyzed in full-thickness epithelium. RESULTS: Human corneas subjected to mechanical strain showed a significantly higher number of BL breaks compared with unstretched controls (2.0 ± 1 vs. 0.4 ± 0.53, P = 0.003). In mouse corneas, mechanical strain increased the basal epithelial cell width by 15% (7.16 ± 1.67 vs. 8.25 ± 1.82 μm, P < 0.001), while reducing the apical cell height by 8% (7.88 ± 1.93 vs. 7.30 ± 1.72, P = 0.025). Wnt10a and Col12a1 mRNA levels were reduced in stretched mouse epithelium compared with unstretched controls (67%, P = 0.0312; 65%, P = 0.0312, respectively). CONCLUSIONS: Eye rubbing is a well-known risk factor for the development and progression of keratoconus. By simulating eye rubbing using our ex vivo cyclical mechanical strain model reproduces changes that occur in early keratoconus. Specifically, this model recapitulates at least 3 elements of the keratoconus phenotype (BL breaks, enlargement of the basal epithelium, and reduction in transcript levels of Wnt10a and Col12a1 ), which makes it a valuable tool for the development of targeted drug therapies for progressive keratoconus.
26Keratoconus: an inflammatory disorder?PubMed
V Galvis, T Sherwin, A Tello, et al.
Eye (Lond). 2015 Jul;29(7):843-59. doi: 10.1038/eye.2015.63. Epub 2015 May 1.
Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.
27Matrix metalloproteinases in keratoconus - Too much of a good thing?PubMed
Erica di Martino, Manir Ali, Chris F Inglehearn
Exp Eye Res. 2019 May;182:137-143. doi: 10.1016/j.exer.2019.03.016. Epub 2019 Mar 23.
Keratoconus (KC) is a progressive, early onset, and often bilateral eye condition, in which the cornea gradually weakens and bulges out, and in advanced cases may eventually become cone-shaped. The available evidence suggests that it is a multifactorial disease with environmental and genetic contributions. Matrix Metalloproteinases (MMPs) are a family of 24 zinc-dependent proteases with the ability to degrade collagen and other extracellular matrix (ECM) proteins, which are important components of the cornea. During the past two decades a growing body of literature has accumulated suggesting a link between MMPs and keratoconus. This article aims to summarize the current knowledge on the role of MMPs in the pathogenesis of KC. MMP-driven ECM remodelling is thought to be a necessary step for cornea healing, but a fine balance in the expression of MMPs is essential in maintaining the integrity and transparency of the cornea and for its correct healing, and an imbalance in this tightly regulated process may, in the long term, result in the progressive weakening of the cornea. There is extensive evidence that MMPs are upregulated in the corneal tissue and tears of KC patients, implicating dysregulated proteolysis in KC, with an increase in the level of some MMPs, particularly MMP-1 and MMP-9, confirmed in multiple independent studies. There is also evidence for a causative link between inflammation, which could result from the mechanical trauma due to contact lens wearing or/and eye rubbing, and the increased MMPs production observed in KC. However, the precise role of each MMP in the cornea is still unclear and the mechanisms causing their upregulation are mostly undiscovered. Further studies are required to verify the functional role of specific MMPs in KC development and assess the genetic association between common MMPs variants and risk of KC. As MMPs inhibitors are in development, this information could potentially drive the discovery of new treatments for KC.
28Effects of Mechanical Compression on Cell Morphology and Function in Human Corneal Fibroblasts.PubMed
Jing Zhang, Shu Yang, Youhua Tan, et al.
Curr Eye Res. 2021 Oct;46(10):1467-1473. doi: 10.1080/02713683.2021.1904510. Epub 2021 May 26.
: To explore the effect of mechanical compression (similar to that induced by eye rubbing) on cell morphology, proliferation, apoptosis, and extracellular matrix synthesis and degradation in human corneal fibroblasts. Human corneal fibroblasts were isolated from corneal lenticule tissue of 10 patients after small incision lenticule extraction surgery. A system was established to mechanically compress corneal fibroblasts with pressure ranging from 0 to 524 Pa. Morphological changes, cell proliferation, apoptosis, and corneal matrix synthesis and degradation were examined using microscopy imaging, bromodeoxyuridine staining, flow cytometry, and qPCR analysis in human corneal fibroblasts after mechanical compression. Human corneal fibroblasts showed short and thick cytoplasmic extensions, as well as a relatively low aspect ratio, suggesting significant morphological alterations caused by high levels of compressive stress. Mechanical compression inhibited cell proliferation and promoted cell apoptosis. Furthermore, compressive stress led to significant elevation in the expression of genes related to extracellular matrix degradation (matrix metalloproteinases and ) as early as 6 h after compression and moderate changes in the expression of tissue inhibitors of metalloproteinases. In addition, the mRNA expression levels of , lumican, and vimentin were reduced 24 and 48 h after mechanical compression. Mechanical compression alters cell morphology, inhibits proliferation, induces apoptosis, upregulates genes related to extracellular matrix degradation, and downregulates corneal structural genes in human corneal fibroblasts. This study provides evidence that compressive stress significantly influences corneal keratocytes. Our findings suggest that this mechanical effect may be related to keratoconus associated with chronic eye rubbing.
29The role of matrix metalloproteinases in infectious corneal ulcers.PubMed
Celia García-López, Marina Rodríguez-Calvo-de-Mora, Davide Borroni, et al.
Surv Ophthalmol. 2023 Sep-Oct;68(5):929-939. doi: 10.1016/j.survophthal.2023.06.007. Epub 2023 Jun 21.
During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis.
30Transforming growth factor beta receptor 2 (Tgfbr2) deficiency in keratocytes results in corneal ectasia.PubMed
Yen-Chiao Wang, Olivia Betty Zolnik, Shingo Yasoda, et al.
Ocul Surf. 2023 Jul;29:557-565. doi: 10.1016/j.jtos.2023.06.014. Epub 2023 Jun 30.
PURPOSE: We hypothesized that Transforming growth factor beta receptor 2 (Tgfbr2) deletion in keratocyte (Tgfbr2), the corneal stroma cell, can result in corneal thinning and generate a potential model for Cornea Ectasia (CE). METHODS: Corneal thickness of Tgfbr2 and Tgfbr2 was examined with Optical Coherence Tomography (OCT) at post-natal (P) days 42 and 70, respectively. Histological H&E staining, transmission electron micrograph (TEM), and immunofluorescence staining (IFS) were harnessed to examine corneal cell morphology, proliferation, differentiation, and collagen fibrils. RESULTS: Slit-Lamp revealed that corneas were transparent in both Tgfbr2 and Tgfbr2, however, Tgfbr2 cornea was 33.5% and 42.9% thinner as compared with those of Tgfbr2 at P42 and P70, respectively. H&E and semithin section staining with toluidine blue-O confirmed that Tgfbr2 cornea has a thinner stroma. In contrast, the epithelium in Tgfbr2 was substantially thicker. The cell proliferation marker Ki67 expression level increased ∼9% in Tgfbr2 corneal epithelium as compared with that in Tgfbr2, however, the Krt14 and Krt12 expression pattern was not obviously changed in Tgfbr2 corneal epithelium. It was noticed that Col1a1 expression was substantially reduced in Tgfbr2 as compared with that in Tgfbr2. TEM showed that keratocytes were unhealthy and stromal collagen fibril density was significantly reduced in Tgfbr2 as compared with that in Tgfbr2 cornea. Moreover, mechanical eye-rubbing on Tgfbr2 resulted in corneal hydrops and edema. CONCLUSION: Tgfbr2 in keratocytes is indispensable for the corneal stroma at postnatal homeostasis. The cornea phenotype manifested in these Tgfbr2 mice resembles corneal ectasia disease in humans.
31The Magnitude of Intraocular Pressure Elevation Associated with Eye Rubbing.PubMed
Daniel C Turner, Christopher A Girkin, J Crawford Downs
Ophthalmology. 2019 Jan;126(1):171-172. doi: 10.1016/j.ophtha.2018.08.025. Epub 2018 Aug 25.
PURPOSE:: To determine the magnitude of IOP elevation associated with eye rubbing STUDY DESIGN:: Experimental Study SUBJECTS:: Three nonhuman primates (NHPs) METHODS:: Three young adult male rhesus macaques were briefly anesthetized with ketamine and dexmedetomidine, and antibiotic ointment was placed in both eyes. The anesthetic was immediately reversed with atipamezole, and the animals quickly recovered. IOP was continuously recorded at 500 measurements per second during the experiment using a validated implantable wireless telemetry system; high-definition video was recorded while the NHP rubbed its eyes to remove the ointment, and rubbing events were marked in the IOP data. The experiment was repeated four times in each NHP, with numerous eye rubs recorded for each session, and these data were marked and the IOP elevation magnitudes were analyzed using NOTOCORD-hem software. MAIN OUTCOME MEASURES:: IOP elevation above baseline IOP due to eye rubbing RESULTS:: IOP increased as much as 310 mmHg due to eye rubbing. The largest IOP elevations were associated with rubbing the eye and orbit with the back of the hand or wrist, rather than the fingers or knuckle. Eye rubs elicited mean IOP elevations of ~80–150 mmHg above baseline for 3–4 seconds, with peak IOP elevations reaching 205–310 mmHg depending on the individual NHP and eye. CONCLUSIONS:: Rubbing the eyes causes momentary IOP elevations that average 109 mmHg above baseline IOP and can exceed 300 mmHg above baseline IOP in NHP eyes.
32Anterior Chamber XEN Gel Stent Movements: The Impact on Corneal Endothelial Cell Density.PubMed
Kevin Gillmann, Giorgio E Bravetti, André Mermoud, et al.
J Glaucoma. 2019 Jun;28(6):e93-e95. doi: 10.1097/IJG.0000000000001200.
INTRODUCTION: Although there are several examples of glaucoma drainage devices' dislocations in the literature, the movement of XEN gel stents is scarcely documented, and the impact of such displacements on the corneal endothelium remains unknown. In light of the recent global market withdrawal of the CyPass microstent over concerns with regard to endothelial cell loss, we present a case of XEN gel stent dislocation into the anterior chamber, with localized corneal damage. CASE REPORT: We describe the case of a 64-year-old female patient who underwent bilateral XEN gel stent implantation for normal-tension glaucoma. While right eye surgery was uneventful, intraocular pressure increased in the left eye, and examination revealed a flat filtration bleb with no microstent visible through the conjunctiva. A 3 mm segment of the XEN stent was visible within the anterior chamber, with corneal contact during eye movement and blinking. Endothelial cell density was measured twice 1 month apart before the XEN gel stent was replaced. DISCUSSION: First, our observations confirm that XEN gel stents can dislocate and advance within the anterior chamber. We speculate that this displacement was caused by regular eye rubbing after surgery. Second, this report illustrates that the position of a drainage device within the anterior chamber is dynamic and significantly influenced by eye movements and blinking. Finally, occasional corneal contact of a XEN gel stent can cause a reduction in endothelial cell density of 2.1% in a month, which represents 46.2% of the annual endothelial loss observed by Tan and colleagues in patients with a Baerveldt tube (4.54% annual decrease).
33Microtrauma-induced recurrent hyphema and secondary glaucoma associated with chronic acetylsalicylic acid use.PubMed
Ufuk Elgin, Emine Sen, Mehmet Y Teke, et al.
Int Ophthalmol. 2012 Feb;32(1):89-92. doi: 10.1007/s10792-012-9517-5. Epub 2012 Feb 2.
To report a case of microtrauma-induced recurrent hyphema and secondary glaucoma associated with voluntary chronic acetylsalicylic acid (ASA) use. A 43-year-old male developed advanced glaucoma in his right eye after a two-month followup period of recurrent microhyphema, which had been induced by strong eye-rubbing. In spite of topical and systemic antiglaucoma medication, as well as topical corticosteroid and cycloplegic drugs and bed rest under hospitalization, the hyphema and glaucoma were not controlled. His medical history revealed that he had been using ASA for 2 years in order to prevent heart attacks. We asked the patient to stop ASA intake and the hyphema cleared considerably on the third day after discontinuation of the drug. One week after stopping ASA, trabeculectomy with mitomycin C was performed without any complications. Glaucoma and recurrent hyphema were controlled after surgery without any medical treatment. Chronic ASA intake may cause recurrent hyphema and secondary glaucoma even after a microtrauma. Medical histories of patients must always be taken, especially in cases of prolonged recurrent hyphema.
34Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy.PubMed
Charles McMonnies
J Optom. 2018 Jan-Mar;11(1):3-9. doi: 10.1016/j.optom.2017.06.002. Epub 2017 Jul 29.
This review examines the role of oxidative stress in damage to cells of the trabecular meshwork and associated impaired aqueous drainage as well as damage to retinal ganglion cells and associated visual field losses. Consideration is given to the interaction between vascular and mechanical explanations for pathological changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may contribute to ischaemia but there is increasing evidence that altered blood flow in a wider sense is also involved. Both vascular and mechanical theories are involved through fluctuations in intraocular pressure and dysregulation of blood flow. Retinal function is very sensitive to changes in haemoglobin oxygen concentration and the associated variations in the production of reactive oxygen species. Reperfusion injury and production of reactive oxygen species occurs when IOP is elevated or blood pressure is low and beyond the capacity for blood flow autoregulation to maintain appropriate oxygen concentration. Activities such as those associated with postural changes, muscular effort, eye wiping and rubbing which cause IOP fluctuation, may have significant vascular, mechanical, reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes the eye to increased oxygen concentration and the risk of oxidative damage in susceptible individuals. However, oxygen concentration in aqueous humour, and the risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen is delivered by a hood which exposes the anterior ocular surface to higher than normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears to be indicated in these cases.
35Effects of mesenchymal stem cell exosomes on trabecular meshwork cells via the NRF2 pathway.PubMed
Li Xu, Peng Xu, Na Song, et al.
J Pharm Pharmacol. 2025 Oct 29. doi: 10.1093/jpp/rgaf101.
OBJECTIVES: Increased intraocular pressure (IOP) is a significant risk factor for primary open-angle glaucoma (POAG). Physiologically, the trabecular meshwork (TM) controls IOP and the secretion of aqueous humor. A change in resistance to aqueous outflow is related to the phagocytic ability of trabecular meshwork cells (TMCs); in addition, alterations in extracellular matrix can also affect the function of TMCs. However, their application has certain limitations due to the nondirected differentiation and tumorigenic effect of stem cells, while their exosomes can reduce side effects and exert the same effects. METHODS: The effects of mesenchymal stem cell exosomes on the extracellular environment and the function of human trabecular meshwork cells were observed, and glaucomato-related proteins as well as the NRF2 signaling pathway were detected. KEY FINDINGS AND CONCLUSIONS: The exosomes could improve the phagocytosis of TMCs, reduce the damage, and lead to some changes in the pathways related to oxidative stress.
36Substances of Interest That Support Glaucoma Therapy.PubMed
Sergio Claudio Saccà, Paolo Corazza, Stefano Gandolfi, et al.
Nutrients. 2019 Jan 22;11(2):239. doi: 10.3390/nu11020239.
Glaucoma is a multifactorial disease in which pro-apoptotic signals are directed to retinal ganglion cells. During this disease the conventional outflow pathway becomes malfunctioning. Aqueous humour builds up in the anterior chamber, leading to increased intraocular pressure. Both of these events are related to functional impairment. The knowledge of molecular mechanisms allows us to better understand the usefulness of substances that can support anti-glaucoma therapy. The goal of glaucoma therapy is not simply to lower intraocular pressure; it should also be to facilitate the survival of retinal ganglion cells, as these constitute the real target tissue in this disease, in which the visual pathway is progressively compromised. Indeed, an endothelial dysfunction syndrome affecting the endothelial cells of the trabecular meshwork occurs in both normal-tension glaucoma and high-tension glaucoma. Some substances, such as polyunsaturated fatty acids, can counteract the damage due to the molecular mechanisms - whether ischemic, oxidative, inflammatory or other - that underlie the pathogenesis of glaucoma. In this review, we consider some molecules, such as polyphenols, that can contribute, not only theoretically, to neuroprotection but which are also able to counteract the metabolic pathways that lead to glaucomatous damage. Ginkgo biloba extract, for instance, improves the blood supply to peripheral districts, including the optic nerve and retina and exerts a neuro-protective action by inhibiting apoptosis. Polyunsaturated fatty acids can protect the endothelium and polyphenols exert an anti-inflammatory action through the down-regulation of cytokines such as TNF-α and IL-6. All these substances can aid anti-glaucoma therapy by providing metabolic support for the cells involved in glaucomatous injury. Indeed, it is known that the food we eat is able to change our gene expression.
37Longitudinal In Vivo Changes in Retinal Ganglion Cell Dendritic Morphology After Acute and Chronic Optic Nerve Injury.PubMed
Delaney C M Henderson, Jayme R Vianna, John Gobran, et al.
Invest Ophthalmol Vis Sci. 2021 Jul 1;62(9):5. doi: 10.1167/iovs.62.9.5.
PURPOSE: To characterize in vivo dendritic changes in retinal ganglion cells (RGCs) after acute (optic nerve transection, ONT) and chronic (experimental glaucoma, EG) optic nerve injury. METHODS: ONT and EG (microbead model) were carried out in Thy1-YFP mice in which the entire RGC dendritic arbor was imaged with confocal fluorescence scanning laser ophthalmoscopy over two weeks in the ONT group and over two and six months, respectively, in two (groups 1 and 2) EG groups. Sholl analysis was used to quantify dendritic structure with the parameters: area under the curve (AUC), radius of the dendritic field, peak number of intersections (PI), and distance to the PI (PD). RESULTS: Dendritic changes were observed after three days post-ONT with significant decreases in all parameters at two weeks. In group 1 EG mice, mean (SD) intraocular pressure (IOP) was 15.2 (1.1) and 9.8 (0.3) mmHg in the EG and untreated contralateral eyes, respectively, with a significant corresponding decrease in AUC, PI, and PD, but not radius. In group 2 mice, the respective IOP was 13.1 (1.0) and 8.8 (0.1) mmHg, peaking at two months before trending towards baseline. Over the first two months, AUC, PI, and PD decreased significantly, with no further subsequent changes. The rates of change of the parameters after ONT was 5 to 10 times faster than in EG. CONCLUSIONS: Rapid dendritic changes occurred after ONT, while changes in EG were slower and associated with level of IOP increase. The earliest alterations were loss of inner neurites without change in dendritic field.
38A mouse ocular explant model that enables the study of living optic nerve head events after acute and chronic intraocular pressure elevation: Focusing on retinal ganglion cell axons and mitochondria.PubMed
Elizabeth C Kimball, Mary E Pease, Matthew R Steinhart, et al.
Exp Eye Res. 2017 Jul;160:106-115. doi: 10.1016/j.exer.2017.04.003. Epub 2017 Apr 14.
We developed an explant model of the mouse eye and optic nerve that facilitates the study of retinal ganglion cell axons and mitochondria in the living optic nerve head (ONH) in an ex vivo environment. Two transgenic mouse strains were used, one expressing yellow fluorescent protein in selected axons and a second strain expressing cyan fluorescent protein in all mitochondria. We viewed an explanted mouse eye and optic nerve by laser scanning microscopy at and behind the ONH, the site of glaucoma injury. Explants from previously untreated mice were studied with the intraocular pressure (IOP) set artificially at normal or elevated levels for several hours. Explants were also studied from eyes that had undergone chronic IOP elevation from 14 h to 6 weeks prior to ex vivo study. Image analysis in static images and video of individual mitochondria or axonal structure determined effects of acute and chronic IOP elevation. At normal IOP, fluorescent axonal structure was stable for up to 3 h under ex vivo conditions. After chronic IOP elevation, axonal integrity index values indicated fragmentation of axon structure in the ONH. In mice with fluorescent mitochondria, the normal density decreased with distance behind the ONH by 45% (p = 0.002, t-test). Density increased with prior chronic IOP elevation to 21,300 ± 4176 mitochondria/mm compared to control 16,110 ± 3159 mitochondria/mm (p = 0.025, t-test), but did not increase significantly after 4 h, acute IOP elevation (1.5% decrease in density, p = 0.83, t-test). Mean normal mitochondrial length of 2.3 ± 1.4 μm became 13% smaller after 4 h of IOP elevation ex vivo compared to baseline (p = 0.015, t-test, N-10). Normal mitochondrial speed of movement was significantly slower in the anterograde direction (towards the brain) than retrograde, but there were more mitochondria in motion and traveling longer lengths in anterograde direction. The percent of mitochondria in motion decreased by >50% with acute IOP increase to 30 mm Hg after 60 min. A new ocular explant model implemented with eyes from transgenic mice with fluorescent cellular components provided real time measurement of the early events in experimental glaucoma and quantitative outcomes for neuroprotection therapy experiments.
39Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats.PubMed
Hana Levkovitch-Verbin, Harry A Quigley, Keith R G Martin, et al.
Invest Ophthalmol Vis Sci. 2002 Feb;43(2):402-10.
PURPOSE: To develop and characterize a model of pressure-induced optic neuropathy in rats. METHODS: Experimental glaucoma was induced unilaterally in 174 Wistar rats, using a diode laser with wavelength of 532 nm aimed at the trabecular meshwork and episcleral veins (combination treatment group) or only at the trabecular meshwork (trabecular group) through the external limbus. Intraocular pressure (IOP) was measured by a tonometer in rats under ketamine-xylazine anesthesia. Possible retinal vascular compromise was evaluated by repeated fundus examinations and by histology. The degree of retinal ganglion cell (RGC) loss was assessed by a masked, semiautomated counting of optic nerve axons. Effects of laser treatment on anterior ocular structures and retina were judged by light microscopy. RESULTS: After the laser treatment, IOP was increased in all eyes to higher than the normal mean IOP of 19.4 +/- 2.1 mm Hg (270 eyes). Peak IOP was 49.0 +/- 6.1 mm Hg (n = 108) in the combination group that was treated by a laser setting of 0.7 seconds and 0.4 W and 34.0 +/- 5.7 mm Hg (n = 46) in the trabecular group. Mean IOP after 6 weeks was 25.5 +/- 2.9 mm Hg in glaucomatous eyes in the combination group compared with 22.0 +/- 1.8 mm Hg in the trabecular group. IOP in the glaucomatous eyes was typically higher than in the control eyes for at least 3 weeks. In the combination group, RGC loss was 16.1% +/- 14.4% at 1 week (n = 8, P = 0.01), 59.7% +/- 25.7% at 6 weeks (n = 88, P < 0.001), and 70.9% +/- 23.6% at 9 weeks (n = 12, P < 0.001). The trabecular group had mean axonal loss of 19.1% +/- 14.0% at 3 weeks (n = 9, P = 0.004) and 24.3% +/- 20.2% at 6 weeks (n = 25, P < 0.001), increasing to 48.4% +/- 32.8% at 9 weeks (n = 12, P < 0.001). Laser treatment led to closure of intertrabecular spaces and the major outflow channel. The retina and choroid were normal by ophthalmoscopy at all times after treatment. Light microscopic examination showed only loss of RGCs and their nerve fibers. CONCLUSIONS: Increased IOP caused by a laser injury to the trabecular meshwork represents a useful and efficient model of experimental glaucoma in rats.
40Neuroprotective effect of memantine in different retinal injury models in rats.PubMed
Elizabeth WoldeMussie, Eti Yoles, Michal Schwartz, et al.
J Glaucoma. 2002 Dec;11(6):474-80. doi: 10.1097/00061198-200212000-00003.
PURPOSE: To evaluate the neuroprotective effect of memantine, an NMDA receptor channel blocker, in two retinal ganglion cell (RGC) injury models in rats. METHODS: Neuroprotective effect of memantine was tested in partial optic nerve injury and chronic ocular hypertensive models. In the optic nerve injury model, memantine (0.1 - 30 mg/kg) was injected intraperitoneally immediately after injury. Two weeks later, optic nerve function was determined by measuring compound action potential and surviving RGC was determined by retrograde labeling with dextran tetramethyl rhodamine. Chronic ocular hypertension was attained by laser photocoagulation of episcleral and limbal veins. Memantine (5 or 10 mg/kg) was administered continuously each day with an osmotic pump, either immediately after or 10 days after first laser photocoagulation, for 3 weeks, after which RGC survival was determined. RESULTS: Two weeks after partial optic nerve injury, there was approximately 80% reduction in RGC number. Memantine (5 mg/kg) caused a twofold increase in compound action potential amplitude and a 1.7-fold increase in survival of RGCs, respectively. In the chronic ocular hypertension model there was 37% decrease in RGCs after 3 weeks of elevated intraocular pressure. Memantine (10 mg/kg daily) reduced ganglion cell loss to 12% when applied immediately after first laser photocoagulation, and prevented any further loss when applied 10 days after first laser photocoagulation. CONCLUSION: The protective effect of memantine suggests that excessive stimulation of NMDA receptors by glutamate is involved in causing cell damage in these RGC injury models.
41Eye-rubbing optic neuropathy.PubMed
Lorenzo Pecora, Paul Sibony, Stuart Fourman
Am J Ophthalmol. 2002 Sep;134(3):460-1. doi: 10.1016/s0002-9394(02)01498-8.
PURPOSE: To describe a patient whose "normal tension glaucoma" appears to have been produced by a long-standing habit of repetitive, bilateral eye rubbing. DESIGN: Observational case report. METHODS: A 46-year-old man presented with a "haze" over the left eye and had progressive bilateral optic neuropathy associated with bilateral normal intraocular pressure, pathological cupping of the optic disks, and nerve fiber bundle visual field defects. RESULTS: Over a 4-year period, vision in the left eye deteriorated to no light perception. Progressive deterioration in the right eye stopped only after the patient ceased a 20-year habit of forceful rubbing of his eyes. After that, the decline in vision was terminated and both visual acuity and visual field were stabilized over an 8-year follow-up. CONCLUSION: It may be appropriate to include "eye rubbing" in the differential diagnosis of unexplained progressive optic neuropathy in presumed normal tension glaucoma.
42Early Optic Nerve Head Glial Proliferation and Jak-Stat Pathway Activation in Chronic Experimental Glaucoma.PubMed
Diana C Lozano, Tiffany E Choe, William O Cepurna, et al.
Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):921-932. doi: 10.1167/iovs.18-25700.
PURPOSE: We previously reported increased expression of cell proliferation and Jak-Stat pathway-related genes in chronic experimental glaucoma model optic nerve heads (ONH) with early, mild injury. Here, we confirm these observations by localizing, identifying, and quantifying ONH cellular proliferation and Jak-Stat pathway activation in this model. METHODS: Chronic intraocular pressure (IOP) elevation was achieved via outflow pathway sclerosis. After 5 weeks, ONH longitudinal sections were immunolabeled with proliferation and cell-type markers to determine nuclear densities in the anterior (unmyelinated) and transition (partially myelinated) ONH. Nuclear pStat3 labeling was used to detect Jak-Stat pathway activation. Nuclear density differences between control ONH (uninjected) and ONH with either early or advanced injury (determined by optic nerve injury grading) were identified by ANOVA. RESULTS: Advanced injury ONH had twice the nuclear density (P < 0.0001) of controls and significantly greater astrocyte density in anterior (P = 0.0001) and transition (P = 0.006) ONH regions. An increased optic nerve injury grade positively correlated with increased microglia/macrophage density in anterior and transition ONH (P < 0.0001, both). Oligodendroglial density was unaffected. In glaucoma model ONH, 80% of anterior and 66% of transition region proliferating cells were astrocytes. Nuclear pStat3 labeling significantly increased in early injury anterior ONH, and 95% colocalized with astrocytes. CONCLUSIONS: Astrocytes account for the majority of proliferating cells, contributing to a doubled nuclear density in advanced injury ONH. Jak-Stat pathway activation is apparent in the early injury glaucoma model ONH. These data confirm dramatic astrocyte cell proliferation and early Jak-Stat pathway activation in ONH injured by elevated IOP.
43Eye rubbing, pillow contact, and corneal endothelial cell density.PubMed
E Raad, G Sukkarieh, J El Helou, et al.
J Fr Ophtalmol. 2025 Dec;48(10):104673. doi: 10.1016/j.jfo.2025.104673. Epub 2025 Nov 3.
INTRODUCTION: While eye rubbing and eye-pillow contact increase the risk of keratoconus, their association with corneal endothelial cell density (ECD) and central corneal thickness (CCT) remains unclear. The goal of this study was to assess the association between these behaviors and corneal ECD and CCT. METHODS: This was a cross-sectional study including 296 otherwise healthy eyes of 162 nondiabetic patients with cataract who underwent non-contact specular microscopy prior to cataract surgery. All patients completed a detailed questionnaire regarding their eye rubbing habits and eye contact with the pillow during sleep. Comparisons of means, correlation tests and one-way ANCOVA test were performed to analyze the data. RESULTS: Eye rubbing was associated with a significantly lower ECD. Eye rubbers had a mean ECD of 2470±275 cells/mm compared to 2611±313 cells/mm in non-eye rubbers (P=0.000), representing a 5.4% lower ECD in eye rubbers. This remained significant after controlling for age (P=0.000). No significant difference in CCT was noted between eye rubbers and non-eye rubbers (P=0.951). No significant differences in ECD (P=0.249) or CCT (P=0.084) were found between eyes with and without eye-pillow contact. A small significant positive correlation was found between ECD and CCT (P=0.008). The endothelial cell loss rate was 0.28% per year of age. DISCUSSION: The lower ECD found in eye rubbers appears to be less clinically significant than changes caused by mechanical stress to the corneal stroma (as seen in keratoconus). The lower ECD in eye rubbers can be explained by elevated intraocular pressure and direct mechanical stress caused by eye rubbing. Further prospective research is needed to analyze in greater detail the association between corneal mechanical stress and corneal endothelial health. In addition, this study is the first to report epidemiological data on ECD and CCT in a Lebanese sample. CONCLUSION: Eye rubbing is associated with a lower corneal endothelial cell density.
44Laser scanning in vivo confocal microscopy reveals reduced innervation and reduction in cell density in all layers of the keratoconic cornea.PubMed
Rachael L Niederer, Divya Perumal, Trevor Sherwin, et al.
Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2964-70. doi: 10.1167/iovs.07-0968.
PURPOSE: The exact pathophysiological processes underlying keratoconus remain an enigma. In this study, laser scanning in vivo confocal microscopy (IVCM) was used to define further the microstructural abnormalities in the keratoconic cornea and to establish the relationship with disease severity. METHODS: This was a prospective, cross-sectional study comparing 52 subjects with keratoconus and 52 age-matched control subjects. Assessment included demographics, history, slit lamp biomicroscopy, computerized corneal tomography, and laser scanning IVCM. RESULTS: Significantly lower cell densities (in cells per square millimeter, mean +/- SD) were observed in keratoconus corneas than in normal ones: basal epithelial cells, 4340.6 +/- 595.2 vs. 5777.6 +/- 958.2 (P < 0.001), anterior keratocytes, 523.6 +/- 206.4 vs. 859.7 +/- 219.1 (P < 0.001), posterior keratocytes, 240.4 +/- 64.5 vs. 330.6 +/- 52.3 (P < 0.001), and endothelial cells 2412.2 +/- 339.5 vs. 2845.6 +/- 313.0 (P < 0.001). Subbasal nerve fiber density was 52.7% lower in keratoconus corneas than in the control (P < 0.001). Basal epithelial cell density (P = 0.001), subbasal nerve fiber density (P = 0.015), and anterior keratocyte density (P < 0.001) correlated with severity of disease. Lower subbasal nerve density also correlated with younger age at diagnosis (r = 0.397, P = 0.004). Severe disease was associated with diagnosis at a younger age (P = 0.023), a history of eye rubbing (P = 0.025), and Maori or Pacific Island ethnicity (P = 0.001). CONCLUSIONS: Significant microstructural abnormalities were identified at every level of the keratoconic cornea and were related to disease severity. IVCM offers a potential insight into the pathophysiology of the microstructural changes in keratoconus.
45Case of late-onset corneal decompensation after iris-fixated phakic intraocular lens implantation.PubMed
Roy van Eijden, Niels E de Vries, Lars P J Cruysberg, et al.
J Cataract Refract Surg. 2009 Apr;35(4):774-7. doi: 10.1016/j.jcrs.2008.09.032.
A 48-year-old myopic patient with bilateral anterior chamber depth of 3.1 mm and endothelial cell density (ECD) of 2525 cells/mm(2) and 2638 cells/mm(2) preoperatively had bilateral implantation of an Artisan iris-fixated phakic intraocular lens (pIOL). Five years postoperatively, unilateral corneal stromal edema was seen in a circumscribed area overlying the temporal ridge of the pIOL in the right eye; the ECD was 1631 cells/mm(2) and the pachymetry, 586 microm. Explantation of the pIOL was refused by the patient. Seven years postoperatively, the ECD was 413 cells/mm(2) in the right eye and corneal decompensation occurred. The progressive unilateral endothelial loss was explained by excessive rubbing of the eyes because of chronic itching and an anterior shift of the pIOL over the 7 years as demonstrated by anterior optical coherence tomography.
46Negative implant. A retrospective study.PubMed
M Landesz, J G Worst, J V Siertsema, et al.
Doc Ophthalmol. 1993;83(4):261-70. doi: 10.1007/BF01204327.
Implantation of a negative power intraocular lens is one of the options for surgical correction of high myopia. We studied 36 eyes with a Fechner Worst Claw Lens, implanted in Groningen between March 1987 and November 1991. The preoperative myopia ranged from -7.00 to -30.00 diopters. Twenty one eyes had a follow up period of more than 12 months. The IOL power was calculated with the van der Heyde method. Correction within 1 diopters of emmetropia has been achieved in 55.5% of the cases. Deviation of more than 2 diopters occurred in 25%. In 24 eyes the best corrected postoperative visual acuity improved. Due to the IOL the retinal image increases in size as compared to spectacle correction. In none of the cases complications were encountered during surgery. In the postoperative period one IOL had to be replaced because of an error made in the calculation of the lens power. In one case endothelial decompensation occurred, probably due to a combination of compulsive eye rubbing and a preexisting cornea guttata. The rim of the IOL optic is the part which is the closet to the endothelium. Our recommendation is that one should avoid indentation of the cornea. No other serious complications occurred in this study.
47Management of a large plant-derived foreign body under the plica semilunaris: a case report.PubMed
Jiao Zhao, Qingqing Zhang, Zhike Xu
BMC Ophthalmol. 2025 Nov 3;25(1):614. doi: 10.1186/s12886-025-04386-0.
BACKGROUND: Foreign bodies are a common cause of eye pain and tears; however, the majority of cases involve small foreign bodies. Herein, we report a rare case of a large plant-derived foreign body covered with thorns penetrating the conjunctiva into the subconjunctival plica semilunaris following vigorous eye rubbing. CASE PRESENTATION: A 50-year-old woman from rural Leshan presented with persistent redness and swelling on the nasal side of her left eye lasting 10 days. The plica semilunaris appeared elevated, congested, and edematous. A sharp plant-derived tip, approximately 1-mm in length, was visible on the nasal aspect of the elevated area. The temporal bulbar conjunctiva appeared pale and semicircular. The foreign body was extracted from the conjunctiva under a slit lamp by grasping the exposed tip. The extracted foreign body, measuring 8 mm in length and 4 mm in diameter, resembled a plant-derived seed with thorns covering its surface. The patient's conjunctival inflammation and discomfort resolved completely following removal and topical treatment. CONCLUSION: When evaluating patients presenting with ocular irritation as the chief complaint, thorough ocular examinations should be performed, particularly considering the possibility of occult foreign bodies. Concurrently, the present case underlines the significance of considering occult subconjunctival foreign bodies in cases of persistent conjunctival inflammation.
48Iris defect management in the context of presbyopia-correcting intraocular lenses.PubMed
Nicole R Fram, Steven G Safran, Eli Pratte, et al.
J Cataract Refract Surg. 2024 Aug 1;50(8):889-894. doi: 10.1097/j.jcrs.0000000000001506.
A 65-year-old man had uneventful cataract surgery in the right eye with a toric diffractive intraocular lens (IOL) placed fully within the capsule bag. On postoperative day 1 and week 1, the IOL was well positioned and his eye was healing normally. The plan was to proceed with cataract surgery in the left eye in the near future. One month postoperatively, he presented with blurred vision, glare, and halos and was noted to have iris prolapse out of the temporal clear corneal main incision. Of interest, the patient reported some itching and eye rubbing in the early postoperative period. He was taken back to surgery by the referring doctor, and despite 2 heroic attempts to reposit and save the iris tissue, there was significant iris loss causing transillumination defects and debilitating glare and halos. Ocular examination revealed an uncorrected distance visual acuity (UDVA) of 20/40 - 2 J3 and binocular corrected distance visual acuity (CDVA) 20/30 J1 in the right eye and UDVA of 20/60 J3 and binocular CDVA of 20/25 J1 in the left eye. Manifest refraction was -0.25 -1.25 × 155 in the right eye and plano -2.25 × 090 in the left eye. Fortunately, there was no relative afferent pupillary defect, and intraocular pressures were normal off all drops. On slitlamp examination of the right eye, pertinent findings revealed a protective ptosis, trace conjunctival injection with 1 large subconjunctival polypropylene flange at 8:30 o'clock 1.5 mm from the limbus and 1 exposed irregular polypropylene flange eroded through the conjunctiva at 10 o'clock 0.5 mm from the limbus (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202408000-00019/figure1/v/2024-07-30T221851Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202408000-00019/figure2/v/2024-07-30T221851Z/r/image-tiff). There was a localized area of erythema and scleral thinning surrounding the exposed flange. The cornea was edematous over the main incision. The iris was disinserted with atrophic changes and a residual iridodialysis extending from 8:30 to 10 o'clock. The trifocal IOL was fully in the capsule bag with trace fibrosis of the capsule and rotated approximately 7 degrees off the capsulotomy tab, designating the intended axis of 1 degree. The anterior chamber was deep and quiet, and the posterior segment was unremarkable with a 0.45 cup-to-disc ratio. Pertinent examination findings in the left eye included a 2 + NS cataract and a 0.45 cup-to-disc ratio. The remainder of the examination was otherwise unremarkable. What testing and surgical plan would you offer this patient? How would you counsel regarding postoperative expectations?
49Pterygium with bulbar conjunctival hemorrhages.PubMed
L Kria, T Amemiya, Y Dake, et al.
Graefes Arch Clin Exp Ophthalmol. 1999 Jun;237(6):468-73. doi: 10.1007/s004170050263.
BACKGROUND: This study was carried out to describe the clinical features and electron-microscopic characteristics of the capillaries in pterygium with conjunctival hemorrhage. METHODS: We compared the clinical findings in Japanese and Tunisian primary pterygia and in pterygium with and without bulbar conjunctival hemorrhages. The capillary fine structures of pterygium with bulbar conjunctival hemorrhages were studied by electron microscopy and compared with those without bulbar conjunctival hemorrhages. RESULTS: Conjunctival hemorrhages were noted in 16.4% of Tunisian patients but not in any Japanese patients. The former pterygia were significantly larger, more vascular and more frequently hyperemic than the latter. Pterygia with bulbar conjunctival hemorrhages were more hyperemic than without hemorrhages. Electron microscopy revealed interruptions of the endothelial cells and basement membrane of the capillaries in the pterygia with bulbar conjunctival hemorrhages, with blood cells escaping through the endothelial interruptions. CONCLUSION: Conjunctival hemorrhage in pterygia may be caused by fragility of the endothelial cells and basement membrane in the capillaries, which easily induces hemorrhage when the eyes are irritated by rubbing or by conjunctival foreign bodies. Pterygium with conjunctival hemorrhage is more frequently found in Tunisians than in Japanese.