Etiology, pathogenesis, and management of acute intraocular lens opacification: a systematic review

INTRODUCTION

Millions of cataract surgeries with intraocular lens (IOL)implantation are performed worldwide per year

.Improvement in surgical techniques and manufacturing of biocompatible and foldable IOLs led to excellent postoperative outcomes. Foldable IOLs are synthesized from different materials. Acrylate/methacrylate polymers and silicone elastomers are the two main groups

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Although cataract surgery brings many advantages to the patients, the risk of various complications is still a concern

.One of the infrequent adverse events that could reduce the patients’ visual acuity and contrast sensitivity is losing the transparency of the IOL

. IOL opacification may lead to IOL removal or exchange, which is unpleasant to both the patient and the surgeon

. A significant proportion of explanted IOLs in an eye center in the United States was secondary to optic opacification or discoloration

. Several reports of acute IOL clouding are available in the literature describing various etiologies of this phenomenon, however, the exact mechanism remained unclear in some cases

. Herein, we aimed to review the causes and outcomes of intraoperative and early postoperative IOL opacification and provide a discussion on prevention from unnecessary IOL explantation in selected individuals.

MATERIALS AND METHODS

The required information was gathered by reviewing various databases including PubMed/Medline, Google Scholar, and Cochrane library, up to September 2021.

We systematically searched the literature using the following keywords: (“intraocular lens opacification” OR “intraocular lens clouding” OR “intraocular lens fogging” OR “intraocular lens discoloration”) AND (“acute” OR “transient” OR “early”OR “reversible” OR “temporary” OR “intraoperative”). No limitations on publication status or study design were imposed.The most relevant papers to IOL discoloration until one month after implantation were collected. The reference list of eligible articles was also explored for additional resources. Finally, all of the selected studies were reviewed.

RESULTS

3.1 本試驗采用了一種新型的軸心抗拉試件，采用粘膠法固定受拉端與試件。試驗表明，兩端端頭混凝土與鋼板的膠結力大于試件的軸拉力。

Temperature fluctuation Reports of acute IOL clouding immediately after implantation of the IOL into the anterior chamber have been discussed, probably related to the storage condition. Transferring of the IOL from the outside temperature below freezing to the theater shortly before surgery is the common point of these studies. Sudden IOL implantation into the eye with a temperature of 37 ℃ is the hypothesized mechanism of this kind of opacification. The haziness was described in the optic plate’s body without surface deposits and tended to be milky white. Both hydrophilic and hydrophobic acrylic IOLs were affected. The opacity was transient and lasted for less than 24h with spontaneous resolution

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Adherence to the manufacture’s guidelines regarding the storage temperature of the IOL is recommended to avoid abrupt changes in the temperature and subsequent aforementioned intraoperative IOL clouding. The underlying mechanism is not well known. A previous case report of IOL clouding in an acrylic hydrophilic IOL suggested that the imbibitions of water following a rapid temperature fulctuation is the causal factor

.Zhang

explained a possible cause in which increasing temperature may lead to microbubble production by releasing the air inside the IOL. This causes light refraction, which appears as IOL clouding

. They also hypothesized that the equilibrium in the air dissolution in the IOL and water would lead to resolution of the clouding after a while. Intraoperative opacification of a hydrophilic acrylic with hydrophobic surface IOL following storage in low temperature was described in a case report. The authors performed an

experiment by placing a CT Spheris 504 IOL in a 37℃ balanced salt solution(BSS) after staying at 4℃ for 24h. The same IOL clouding occurred. They mentioned that consolidation of water vapor on a cold surface might explain the observed discoloration, which resolved within 24h

. A previously reported study described a transient AcrySof IOL fogging after warming in a heating cupboard at 47℃ . They used this practice as a way to simplify and facilitate IOL implantation. The lens was clear before folding and the clouding occurred after unfolding into the eye. The IOL was removed and kept dry at room temperature,which led to spontaneously disappearance of opacity after 3h.The reason of the glistening was thought to be the hydration secondary to temperature rise and subsequent microvacuole formation. Dehydration after several hours after keeping the lens in a dry place would cause spontaneous clearing. They also encountered another similar case and therefore advised not to store an acrylic IOL at a temperature above 45℃ .The implant should preferably keep at room temperature to avoid glistening

. A similar glistening formation related to the presumed temperature change of the packaging system’s microenvironment in the first postoperative week was earlier described

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當然，權衡各種糾紛解決機制，在保護投資者權益方面，應該堅持以訴訟為主導的思路?？梢越梃b2003年《最高人民法院關于審理證券市場因虛假陳述引發的民事賠償案件的若干規定》中的做法，引入有限制的舉證責任倒置規則，一定程度上解決投資者舉證困難的問題。此外，我國還應盡快出臺專門針對金融投資者權益保護的法律法規或司法解釋，從而為法官審理案件提供統一的司法依據。

Another published report of early postoperative opacification discussed a patient with cataract and dense vitreous hemorrhage who underwent a triple pars plana vitrectomy,phacoemulsification, and IOL implantation. On the third postoperative day, many small brown corpuscles with the appearance of a dusty haze were seen on the lens surface.The IOL was a single-piece AcrySof acrylic (SA60AT, Alcon,USA). The surgeons explanted and exchanged it with another same type of lens which remained clear. After analysis,proteinaceous material (particularly fragments consisting of 17 aminoacids) was identified on the IOL surface but there was no triamcinolone or calcium. A probable theory is the adherence of the hemocyte element of the residual vitreous hemorrhage to the adhesive AcrySof surface

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Evaluation of interaction between different IOLs (PMMA,silicone, three-piece hydrophobic acrylic, single-piece hydrophobic acrylic, and single-piece hydrophilic acrylic) and trypan blue 0.1%, fluorescein sodium 2%, and indocyanine green (ICG) 0.5% revealed that only the hydrophilic acrylic materials uptake the dye and get stained. The most significant color change occurred with the use of fluorescein. Careful irrigation of dye can be helpful to avoid lens staining. In addition, the authors do not recommend hydrophilic acrylic IOLs when intraocular dyes are required

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Olson

later reported the IOL crystallization in 0.07% of cataract surgeries. The previous theory that described Healon GV as the only culprit in the formation of intraoperative crystallization was rejected because some cases were occurred using Amvisc Plus, Occucoat, and other viscoelastics. The degree of crystallization of polymethyl methacrylate (PMMA)IOLs was minimal, and all the significant cases had been noted with silicone IOLs. Correlation with BSS Plus was also statistically significant. The analysis of samples by scanning electron microscopy and X-ray photoelectron spectroscopy showed calcium-containing deposits. They assumed that the osmotic gradient created by using viscoelastic is responsible for calcium deposition on the IOL surface. The authors recommend IOL exchange in terms of encountering to this phenomenon in the operating room

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Another study in 2006 reported two patients who developed significant granular and crystal-like deposits on the surfaceof single-piece hydrophobic acrylic IOLs immediately after injection into the eye (loaded with Viscoats and Healon GVs, respectively). IOLs were removed and analyzed. They did not find calcium on the surface of lenses and liquid chromatography/mass spectroscopy showed albumin and hemoglobin, which are typically found in aqueous. They hypothesized that crystallization and drying out of OVDs could occur during IOL loading in the cartridge. Various gross appearances could be seen based on the type of viscoelastic used

. Plastic exfoliations from the cartridge may result in intraoperative deposits between the IOL and posterior capsule when the hydrophilic acrylic lens is implanted without viscoelastic

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Early Postoperative Intraocular Lens Opacification We assessed cases of IOL clouding up to one month after surgery.Here the classifications are provided based on the presumed etiologies. Some of the mentioned underlying pathologies occurred before the IOL implantation but we put them in the postoperative category because no opacity was noted during the surgery. There are different explanations for it. First,elapsing of time is required for interactions to cause visible haziness. Second, there is a possibility of preexisting opacity,which is missed by the surgeon due to poor visualization through a surgical microscope.

Intraocular lens contamination, manufacturing defects,and changing hydrophilicity

The manufacturing process,IOL design, and material are essential features for evaluating the causes of decreasing in IOL transparency. Surgeons and scrub nurses may miss the preexisting haziness of the IOL because of viewing through the surgical microscope with lower magnification and higher illumination in comparison to postoperative slit-lamp examination

. The quality control of all production steps will help to avoid IOL opacification and additional surgery for IOL removal.

Opacification of the silicone optic of an Allergan Medical Optics SI18NB lens was noted seven days after surgery. A nucleus-shaped brown discoloration in the central area was attributed to a material defect and low molecular weight silicone fractions not cross-linked during the manufacturing process. Light scattering from water vapor that diffused into the silicone material in the anterior chamber caused a brown haze.This finding was stable in follow-up visits and did not affect the patient’s visual acuity

. Others stated that the interaction with some intracameral medications, inadequate filtering, or instability of silicone material could lead to discoloration of silicone IOLs

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隧道工程支護施工技術科學合理準確的使用是保證隧道安全施工作業的基礎性條件。大家知道，隧道內部的排水系統的施工難度是非常大的，而且施工的綜合性比較強，因此隧道結構防水技術的合理準確的應用要根據施工現場的實際情況而定。通常隧道結構防水的基本原則是“防水、排水、堵水相結合”，常用的施工方法就是在隧道洞的兩側挖掘排水渠、在隧道洞口上方建造截水溝，在隧道內部水溝的出水位置安裝保溫包頭。同時還要密切關注隧道施工縫、變形縫處的排水系統的設計和建造工作。

Another similar event observed with the same IOL, SI-40NB IOL (Allergan) showed a brown haziness the day after surgery.Incubation of the explanted lens in saline at room temperature did not change the opacity after two months. Microscopic examination exhibited numerous abnormal spheroid structures in the central area far from the surface. They hypothesized that it could be related to the chemical compositions of the Allergan silicone IOL or the sterilization process with ethylene oxide gas exposure. The incorporation of water into silicone IOL may be the responsible pathologic phenomenon.Adequate resolution of this type of clouding is unlikely over time, and IOL exchange is often necessary to improve visual function

. However, a case report in 2011 described a diffuse translucent milky white haziness throughout the substance of an AMO Z9002 silicone lens one day after uncomplicated cataract surgery. Clearing of the lens periphery was observed eight days after surgery. The central haze disappeared as well on postoperative day 14. Contamination with industrial chemicals is possible during the manufacturing, sterilization,or packaging process. The mechanism used to explain the initial clearing of the lens periphery was the entrapment of gas or liquid molecules in the lens material and releasing them into the anterior chamber based on the law of diffusion. The peripheral part of the IOL is thinner than the central area. So,less time is required for the diffusion of the contaminants.Besides that, the lens epithelial cells in the capsular bag may have some role in the rapid resolution of opacity in the periphery. A similar pattern of clearing in the same IOL design should be closely visited due to the possibility of spontaneous resolution with excellent visual gain

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Werner

published data from an analysis of 6 explanted 3-piece silicone lenses due to optic opacification a few hours following implantation. Gross and microscopic studies showed that the IOLs became clear at dry state but whitened during hydration. Gas chromatography/mass spectrometry (GC-MS)analysis was performed. Suspect exogenous chemicals (general classes: terpenes and ketones) were found. These compounds are used in industrial cleaning agents and fumigants. Most IOL packages are semipermeable for the sterilization process.The introduction of contaminants and chemicals through these packages is possible

aerosolizing solutions during the disinfection of the storage rooms. This could result in changes in the material toward hydrophilicity and allowing water entrance after implantation in the eye. Further evaluation revealed that all 6 IOLs were kept in the a same place in Brazil preoperatively

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Intraoperative Intraocular Lens Opacification Intraoperative IOL opacification is defined as when the surgeon noticed the opacity during the operation. It is responsible for the majority of acute IOL clouding cases in the literature. Different etiologic categories are discussed in the following sections.

(3)一定量的鋁分別與一定量的鹽酸和NaOH溶液反應,若產生H2的體積比為,則必定是:鋁與鹽酸反應時,鋁過量而鹽酸不足;鋁與NaOH溶液反應時,鋁不足而NaOH溶液過量。

Gray white to faint brown discoloration of an Array SA40N silicone multifocal IOL 1wk after implantation was reported to be related to lens hydration. After 3mo, the patient presented with a blurry vision, which finally led to IOL removal. Light microscopic analysis of the explanted lens was negative for any deposits on or within the IOL material. A chromatographic peak for lidocaine was also noted. Keeping the lens in a dry state resulted in gradual clearing from the peripheral area toward the center. Permeability of the lens material to water and increasing hydrophilicity was attributed to processing defects

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IOL opacification may have severe adverse effects on visual function and contrast sensitivity

. Several pathologic processes have been proposed for the loss of transparency of the implanted IOLs

. Although no direct cause and effect relationship was demonstrated, knowledge of these different mechanisms and patterns of IOL clouding is essential for cataract surgeons. It could guide them to make the best decision for their patients.

2018年培訓內容和形式已逐漸趨向成熟。考慮以后將手機、電腦聯機，操作通過掃描大屏二維碼注冊使用中、外文數據庫，演示檢索過程，讓新員工有更直觀的認識和更深入地參與?！?br>