Introduction: Cataract extraction is the most frequently performed ophthalmological procedure worldwide. Posterior capsule opacification remains the most common consequence after cataract surgery and can lead to deterioration of the visual performance with cloudy, blurred vision and halo, glare effects. Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy is the gold standard treatment and a very effective, safe and fast procedure in removing the cloudy posterior capsule. Damaging the intraocular lens (IOL) during the treatment may occur due to wrong focus of the laser beam. These YAG-pits may lead to a permanent impairment of the visual quality. Methods: In an experimental study, we intentionally induced YAG pits in hydrophilic and hydrophobic acrylic IOLs using a photodisruption laser with 2.6 mJ. This experimental study established a novel 3D imaging method using correlative X-ray and scanning electron microscopy (SEM) to characterize these damages. By integrating the information obtained from both X-ray microscopy and SEM, a comprehensive picture of the materials structure and performance could be established. Results: It could be revealed that although the exact same energies were used to all samples, the observed defects in the tested lenses showed severe differences in shape and depth. While YAG pits in hydrophilic samples range from 100 to 180 µm depth with a round shape tip, very sharp tipped defects up to 250 µm in depth were found in hydrophobic samples. In all samples, particles/fragments of the IOL material were found on the surface that were blasted out as a result of the laser shelling. Conclusion: Defects in hydrophilic and hydrophobic acrylic materials differ. Material particles can detach from the IOL and were found on the surface of the samples. The results of the laboratory study illustrate the importance of a precise and careful approach to Nd:YAG capsulotomy in order to avoid permanent damage to the IOL. The use of an appropriate contact glass and posterior offset setting to increase safety should be carried out routinely.

Cataract surgery is the most common surgical procedure in ophthalmology with >30 million operations worldwide every year. The removal of the cloudy lens and implantation of an artificial intraocular lens (IOL) is considered safe and leads to an improvement in visual performance. However, as with any operation, there are intraoperative and postoperative risks and side effects. The most common postoperative side effect is secondary cataracts and development of posterior capsule opacification (PCO) [1]. A study by Ursell et al. [2], which included over 20,000 eyes, observed that the incidence of PCO ranged between 4.7 and 18.6% at 3 years and 7.1–22.6% at 5 years. The numbers in this context exhibit considerable variation due to the influence of numerous factors. These include the surgery itself and characteristics of the IOL (including material, geometry or edge design), as well as its positioning in the capsule [3‒6]. Neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers can address this problem through a so-called posterior capsulotomy, allowing the patient to restore clear vision, often immediately after the procedure. It may also have positive effects on glare and contrast sensitivity in some cases, improving the overall quality of vision. Nd:YAG laser capsulotomy is considered a very safe and effective method. However, this can also lead to complications. One of the most frequent possible negative effects is the formation of so-called YAG pits. These are tiny defects within the IOL that occur when the laser therapy beam is incorrectly focused not on the posterior capsule itself but on the surface of the IOL. Various studies have already investigated the possible negative effects [7, 8]. With this experimental study, we wanted to evaluate these defects even more precisely using a nondestructive, high resolution imaging correlative X-ray and electron microscopy approach.

We used a Q-switched Nd:YAG laser system (Visulas YAG III, Carl Zeiss, Germany) with wavelength of 1,064 nm and pulse length of <4 ns. Lenses were placed within a self-constructed transparent glass cuvette, which was fixed to the head- and chin rest of the device. The aiming beam was focused directly on the surface of the IOL and also within the IOL material body to intentionally create defects. In all cases the exact same energy level of 2.6 mJ was used. The procedure was performed in exactly the same way with hydrophilic acrylic IOLs (Aspira-aXa, HumanOptics, Germany) and hydrophobic acrylic IOLs (Primus-HD, OphthalmoPro, Germany), both aspheric, monofocal single-piece foldable IOLs with 19.0 D power [9, 10]. The hydrophilic lens has a water content of 26%, a refractive index of 1.46 and an Abbe number of 56. The hydrophobic lens has a water content of <2%, a refractive index of 1.47 and an Abbe number of 57.

X-ray microscopy (XRM) was conducted using a ZEISS Xradia 620 Versa microscope. X-ray microscopy has gained prominence in various fields, including medical applications and material science, due to its non-destructive 3D observation capabilities [11‒13]. In contrast to conventional CT using X-ray sensitive detectors, an alternative approach involves converting X-rays to visible light to facilitate further magnification with glass lenses, achieving sub-micron resolution in micro-CT scanners with the added possibility to enhance the propagating phase contrast using low energy X-rays. In contrast, scanning electron microscopy (SEM) provides high-resolution 2D imaging along with the ability to perform site-specific material characterization, enabling the analysis of localized features at the nanoscale. By integrating the information obtained from both X-ray microscopy and SEM, a comprehensive picture of the materials structure and performance can be established.

For the examination of IOLs in the XRM, the lenses were delicately prepared by placing them softly between two filter paper sheets. They were taken with tweezers and positioned between the papers. To secure the paper sheets, they were wrapped with Kapton tape. This meticulous preparation aims to enable the lenses to rotate smoothly in the CT without any movement of the lens which would result in loss of resolution. Both overview images and high-resolution scans were taken for lens examinations. The chosen scan parameters were an acceleration voltage of 40 kV with an X-ray power of 3 W. This low energy without filtration allows for optimal contrast in the given material [14]. A pixel size of 5 µm was used for overview images to examine defects across the entire lens. Region of interest scans were then conducted with a voxel resolution of 300 nm. This approach allows for obtaining statistical information about the entire lens as well as very detailed information about the YAG pits with very high resolution. What makes the used XRM special is that, due to the employed scintillator technology, magnification is not solely achieved through geometric enlargement. In this study, we can harness the propagation phase contrast in addition to the absorption contrast of a conventional µCT, selectively amplifying it. This allows us to achieve excellent contrast in the YAG pits with the highest resolution.

After the XRM examinations, the selected YAG pits from samples were examined using SEM. The relative positions of the YAG pits were determined and measured using the XRM, ensuring that the exact same YAG pit could be examined in SEM. SEM was performed using a ZEISS Gemini SEM 300 instrument at the Central Facility for Electron Microscopy, RWTH Aachen University. Analyses were conducted under variable pressure (VP) conditions using N2 at 30 Pa at a working distance of 8.5 mm, with an accelerating voltage of 10 kV. The use of this special VP mode was necessary since the samples are not conductive, which is a requirement for SEM investigations.

For the data analysis, the DragonFly software from ORS (ORS, Object Research Systems Montréal Canada, Member of the Comet Group) was utilized in the Pro variant. The data segmentation was performed using Threshold Segmentation.

IOLs were examined using both X-ray and electron microscopy. In this study, hydrophilic lenses were compared to hydrophobic lenses that underwent the same laser processing parameters. Special attention was given to the precise size and manifestation of YAG pits, as well as potential defects in the near-surface region. For both inspected samples, material parts (IOL-fragments) were found on the surface next to the defects which we investigated more in detail.

The hydrophilic lens was initially examined using X-ray microscopy. A multitude of YAG pits were identified on this lens. Measurement of the YAG pits revealed penetration depths ranging from 100 to 180 µm. For a detailed evaluation of the structure and shape of the YAG pits, a characteristic YAG pit was measured using high-resolution XRM. A sectional image of the examined YAG pit is depicted in Figure 1. Furthermore, the reconstructed volume of the YAG pit is represented in blue below. The observation revealed that these YAG pits within the hydrophilic lens, upon reaching the surface, develop into a tube with a voluminous end within the material.

Fig. 1.

XRM investigation of a defect in both hydrophilic and hydrophobic lens reveal severe differences in shape and depth. While YAG pits in hydrophilic samples only range from 100 to 180 µm depth with a round shape tip, very sharp tipped defects up to 250 µm in depth can be found in the hydrophobic samples.

Fig. 1.

XRM investigation of a defect in both hydrophilic and hydrophobic lens reveal severe differences in shape and depth. While YAG pits in hydrophilic samples only range from 100 to 180 µm depth with a round shape tip, very sharp tipped defects up to 250 µm in depth can be found in the hydrophobic samples.

Close modal

In strong contrast are the findings of the YAG pits within the hydrophobic lens, also depicted in Figure 1 on the right side. Initially noticeable is the significantly greater depth of the examined YAG pit, as indicated by the statistical analysis in the overview scan, revealing penetration depths ranging from 130 to 250 µm. Additionally, the shape of the YAG pits is distinctly different. In the hydrophobic lens, these YAG pits converge sharply from the crater on the surface. Furthermore, bright areas are observed along and at the end of the YAG pit. These represent locations where the material has undergone local compaction, exhibited a higher absorption coefficient and consequently appeared bright in the reconstructed XRM slice. Such material compactions were not found to the same extent in the hydrophilic samples.

To investigate the effects of laser irradiation on lenses more precisely, a correlative X-ray microscopy and electron microscopy study was conducted on two impact craters. The results of this investigation are shown in Figure 2. The specific focus of this further study was on the influence of laser irradiation directly at the lens surface, depending on the water content of the lenses.

Fig. 2.

Comparison of the manifestation of YAG pits on the surface of hydrophilic and hydrophobic lenses using SEM backscattered electron images and XRM. 3D representation of a YAG pit for each lens, illustrating the extent of the defect in the volume. Material protrusions on the surface of both lenses can be depicted, likely arising during the processing. Additionally, presence of NaCl crystals, originating from the solution in which the lenses were immersed, can be observed. The damage pattern on the surface appears similar for both lenses and resembles that of a brittle fracture, with radial cracks extending across the lens surface. However, the manifestation in volume looks completely different: in the case of hydrophilic lenses, the profile exhibits a bulbous end, while the hydrophobic lenses display a very sharp profile that penetrates significantly deeper into the material.

Fig. 2.

Comparison of the manifestation of YAG pits on the surface of hydrophilic and hydrophobic lenses using SEM backscattered electron images and XRM. 3D representation of a YAG pit for each lens, illustrating the extent of the defect in the volume. Material protrusions on the surface of both lenses can be depicted, likely arising during the processing. Additionally, presence of NaCl crystals, originating from the solution in which the lenses were immersed, can be observed. The damage pattern on the surface appears similar for both lenses and resembles that of a brittle fracture, with radial cracks extending across the lens surface. However, the manifestation in volume looks completely different: in the case of hydrophilic lenses, the profile exhibits a bulbous end, while the hydrophobic lenses display a very sharp profile that penetrates significantly deeper into the material.

Close modal

Within the CT slices of the surface, no significant difference could initially be observed. Both lenses exhibited an inclusion crater from which radially extending cracks were portrayed. Furthermore, the SEM study was conducted precisely on these impact craters, as shown in the first row of Figure 2. The fracture pattern of the YAG pits can be clearly depicted here, resembling the brittle fracture of glass. At this stage of the investigation, it was already noted that the hydrophobic lens reacts more sensitively to the electron beam. Consequently, the direct surface next to the crater is marked by a relief-like pattern. This effect is not attributable to the laser irradiation. However, a common observation for both lens samples (hydrophilic and hydrophobic) is the presence of particles (fragments) on the surface. This can be shown well in the video which is available as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000539243).

Figure 3 presents a detailed 3D rendering of the YAG defect in the hydrophilic sample. Three types of defects are observable. Firstly, an altered microstructure is evident directly adjacent to the defect, potentially stemming from a laser cross-shot. Secondly, at the border of the defect, there is a material exaggeration, likely resulting from highly localized material melting induced by the laser impact. Lastly, numerous small particles on the surface are visible in Figure 3. These particles, confirmed by EDS, consist of the same material as the lens material and therefore represent residues from the laser damages. The energy-dispersive X-ray spectroscopy analysis performed on these particles demonstrated that they consist of the same carbon material as the lenses. Moreover, NaCl crystals were found on the surface of the samples as shown in yellow in Figure 4. These salt crystals originate from the solution in which the lenses are stored. These two types of particles are also clearly depicted in the reconstructed 3D volume. It is evident that the particles are distributed over considerable distances next to the crater. This is therefore the definitive proof that material particles are detached from the lens by the laser bombardment.

Fig. 3.

Detailed rendering of the YAG defect in the hydrophilic sample showing (1) altered structure next to the defect (2) material posing at the corners of incident crater and (3) loose particles next to the defect which are the result of the laser ablation. Magnified view of particles shown in second row of the figure.

Fig. 3.

Detailed rendering of the YAG defect in the hydrophilic sample showing (1) altered structure next to the defect (2) material posing at the corners of incident crater and (3) loose particles next to the defect which are the result of the laser ablation. Magnified view of particles shown in second row of the figure.

Close modal
Fig. 4.

Energy dispersive spectroscopy (EDS) of the hydrophobic sample showing two kinds of particle on the surface next to the defect. This chemical analysis reveals two types of particles (1) NaCl crystals as residuals of the liquid the lenses were carried but also (2) particles which have the same chemistry as the lens material. These particles stem from laser ablation (note the relatively large surrounding structural change marked with red ordinates from the impact of the electron beam on the sample).

Fig. 4.

Energy dispersive spectroscopy (EDS) of the hydrophobic sample showing two kinds of particle on the surface next to the defect. This chemical analysis reveals two types of particles (1) NaCl crystals as residuals of the liquid the lenses were carried but also (2) particles which have the same chemistry as the lens material. These particles stem from laser ablation (note the relatively large surrounding structural change marked with red ordinates from the impact of the electron beam on the sample).

Close modal

Moreover, in addition to the YAG damages originating from the surface, defects were analyzed that exist solely within the lens and are not connected to the surface. A segment of these defects is illustrated exemplarily in Figure 5. The size of these defects is, in part, half the width of the whole lens thickness.

Fig. 5.

Internal defects in the hydrophobic lens with no connection to the lens surface. These YAG pits also have a large expansion in relation to the total thickness of the lens.

Fig. 5.

Internal defects in the hydrophobic lens with no connection to the lens surface. These YAG pits also have a large expansion in relation to the total thickness of the lens.

Close modal

Nd:YAG laser posterior capsulotomy is performed for PCO, the most common consequence of cataract surgery that typically manifests within months or years of cataract surgery. A study based on the Intelligent Research in Sight Registry dataset found that 28% of eyes developed PCO within 1 year of surgery (10% requiring Nd:YAG capsulotomy), with the mean time to diagnoses being 5–6 months. Another meta-analysis of studies estimated a PCO rate of 11.8% at 1 year, 20.7% at 3 years, and 28.4% at 5 years after cataract surgery [15]. So called IOL pitting may occur in 15–33% of eyes during Nd:YAG capsulotomy and is thought to be caused by incorrectly adjusted focus of the laser beam during the procedure [16]. The characteristics of IOL pitting vary depending on the IOL material, and the surgeon’s experience can greatly reduce the IOL damage during Nd:YAG capsulotomy. Moreover, there are other safety features that should be carried out routinely. The “laser offset” moves the point of laser convergence farther posterior to the HeNe light beam. This is helpful because the optical focus breaks down in the vitreous, and the shock wave is transmitted anteriorly. This setting also decreases the odds of lens damage, particularly in modern IOL designs where there is no space between the capsule and the posterior surface of the IOL [16]. The use of the correct contact glass (“Abraham lens”) is very important and increases safety. It was shown in a prospective, longitudinal study that the use of a contact glass decreases the amount of energy used to remove the fibrosis/PCO [17]. It also improves the focusing and stabilization effect of the eye and can thus avoid complications. The contact lens increases the cone angle of the laser beam. This decreases the required energy to reach optical breakdown and thus increases the safety margin.

In the past, experimental studies already revealed that defects in hydrophobic lenses appeared bigger and were visible with less magnification than in hydrophilic lenses. Similar results were obtained with ESEM images where the defects in hydrophobic IOLs seemed to be frayed while defects in hydrophilic IOLs were of circular shape. Raman spectroscopy showed deeper defects in hydrophobic lenses. The area of chemical changes was greater than the visible defect area [18]. Another study proved that µCT is excellently suited to examine an acrylic IOL in detail, analyze optics and haptics in three dimensions, and to describe all kinds of changes within the IOL without damaging it [19].

Other experimental studies evaluating IOLs on the optical bench confirmed that YAG-pits can reduce imaging quality of IOLs. These defects behave as a new Huygens source, distribute a spherical wave that additionally illuminate the background of the USAF target. The authors assumed that material properties of the IOL (water content, refractive index) play an important role and affect results. They concluded that the impact level is strongly dependent on the number, size and position of these defects (YAG-pits) within the optic [20].

Another experimental study confirmed that the IOL image performance deteriorates with YAG-pits. The total intensity of transmitted light (without scattering) was significantly reduced in the wavelength between 450 and 700 nm and the contrast was significantly reduced. The USAF test targets showed much worse results compared to unmodified counterparts [20].

Correlative X-ray and electron microscopy in this study revealed that, depending on the lens used, the defect pattern appears entirely different under the same laser parameters. The distinctive distinction between the lenses lies in the water content, which is 26% in the hydrophilic acrylic IOL and <2% in the hydrophobic acrylic IOL, respectively.

Firstly, it should be noted that IOLs are made of different materials. While hydrophobic lenses typically consist of crosslinked copolymers of acrylic esters and other acrylic ester co-monomers, with a carbon backbone and ester side groups [21], hydrophilic lenses are made with additional hydroxyl groups introduced in the side chains [22]. It is not surprising, given this fundamental difference, that the defects appear dissimilar. The distinct material behavior was also observed in SEM examinations, where the hydrophobic lens exhibited a much stronger reaction to the electron beam. Choudhury et al. [23] demonstrated in a study that laser drilling in a PMMA polymer results in holes with thin entry holes and round cavities, while in other polymers, it tends to produce larger entry holes and smaller exits. These findings can be correlated with the results of this study, providing a potential explanation for the shape of the defects.

Secondly, the varying water content could lead to different evaporation behaviors. An essential process parameter in thermal drilling is the process gas pressure [24], which determines how the material is expelled from the borehole or, in this case, the defect. For this reason, it can be assumed that due to the higher water content, the material evaporates more abruptly, resulting in the formation of round cavities in the material.

Moreover, polymer materials processed by laser exhibit a phenomenon known as a self-defocusing effect. This implies that, depending on the refractive index of the lens, the material may defocus the laser more or less strongly, leading to varying rates of material removal [25]. These differences can be exploited to increase the ablation rate. In this study, the hydrophobic samples with the higher refractive index demonstrated a significantly greater depth of defects.

Defects in IOLs can arise if the Nd:YAG laser therapy beam is focused incorrectly during posterior capsulotomy. These tiny defects on the IOL surface or within the IOL can have a negative impact on the visual performance. Our experimental study established a novel 3D imaging method using correlative X-ray and SEM to characterize these damages. By integrating the information obtained from both X-ray microscopy and SEM, a comprehensive picture of the materials structure and performance could be established. The YAG pits in the hydrophilic acrylic samples had a depth of 100–180 µm and showed a splinter shaped configuration with a round end. The YAG pits in the hydrophobic acrylic samples showed a more pronounced defect (like shattered glass) with a depth of 100–250 µm and a more conical, tapered shape. Hydrophilic and hydrophobic samples showed lens fragments and particles on the surface of the IOL as a kind of blow out effect as a result of the laser procedure. These effects on the optics of the lens show that Nd:YAG capsulotomy should be performed with maximum precision to avoid such iatrogenic defects. The use of an appropriate contact glass and posterior offset increases safety and reduces the chance of lens pits and should be carried out routinely.

Limitations

This was a laboratory experiment. The laser pits were generated with the IOL in air. Therefore, results may differ from the real-world scenario due to factors such as aqueous humor and cornea. Even if those factors are likely to play a relatively insignificant role, it should be taken into account. For this reason, further experiments are currently being carried out by the authors to take these factors into account.

An ethics statement was not required for this study type, no human or animal subjects or materials were used.

The authors (Andreas F. Borkenstein, Adrian Mikitisin, Alexander Schwedt, Eva-Maria Borkenstein, Joachim Mayer) declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study was conducted without funding or sponsorship by companies or sponsors.

The authors (Andreas F. Borkenstein, Adrian Mikitisin, Alexander Schwedt, Eva-Maria Borkenstein, Joachim Mayer) received no financial support for the research, authorship, and/or publication of this article.

All authors (Andreas F. Borkenstein, Adrian Mikitisin, Alexander Schwedt, Eva-Maria Borkenstein, Joachim Mayer) provided substantial contributions to data acquisition or data analysis and interpretation. AFB came up with the idea for the study, defined the study design, drafted the article and critically revised it. All authors (A.F.B., A.M., A.S., E.-M.B., J.M.) approved the final version to be published.

The authors (Andreas F. Borkenstein, Adrian Mikitisin, Alexander Schwedt, Eva-Maria Borkenstein, Joachim Mayer) confirm that the data supporting the findings of this study are available within the article. Further inquiries can be directed to the corresponding author.

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1
):
014909
.