The material quality of a new hydrophobic acrylic intraocular lens

Background The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well established in-vitro laboratory method, we evaluated a new IOL material’s resistance to glistenings formation. Methods An in-vitro stress test for glistenings induction was performed on twenty samples of hydrophobic acrylic IOLs: ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm 2 ) was evaluated in five sections of each IOL. The results for each model were compared and rated on the Miyata Scale for grading glistening severity.


Background
Hydrophobic acrylic intraocular lenses (IOLs) can develop a whitish, opaque material change under certain environmental conditions or over time. [1,2] This appearance is caused by fluid-filled microvacuoles, so called glistenings, that were first described in 1984. [3] Early hydrophobic acrylate IOL materials were composed of copolymers that allowed low equilibrium water content of below 1%. In these materials, water that enters the polymer, can collect in pockets of lower polymer density. These pockets can enlarge over time until they become discreet vacuoles of water visible as glistenings or subsurface nanoglistenings. [4] Vacuoles with diameters from less than 200 nm up to 120 µm are called subsurface nanoglistenings. [5] The Acrysof hydrophobic acrylic IOL material (Alcon, Fort Worth, USA) has become increasingly popular since the 1990s and is now a widely used IOL material that is approved by all regulatory authorities around the world. Since its introduction, increasing light scattering due to glistenings formation has been observed in lenses made from Acrysof IOL material. [6] Miyata et al. introduced a clinical grading system based on the number of particles seen in slit-lamp examination. [7] To better study glistenings in-vitro, accelerated aging methods have been developed to intentionally generate ex-vivo glistenings. [1] Then, in accordance with the clinical grading system, IOLs can be divided into different glistenings categories depending on the number of microvacuoles per square millimetre that are produced after the aging procedure. Using such methods, the impact of glistenings on the optical performance has been studied and is now well understood.
Glistenings have a rather small effect on the central image quality; their impact on light scattering, on the other hand, is greater. [8,9] We evaluated, using an established in vitro laboratory method, the material quality and stability of a new hydrophobic IOL, one which the manufacturer claims is more resistant to glistenings formation: the Eyecryl Plus ASHFY600, and compared it to the well-established and accepted AcrySof IQ SN60WF.

Intraocular lenses
Ten monofocal Eyecryl Plus ASHFY600 IOLs (Biotech Vision Care, Ahmedabad, India) and ten monofocal AcrySof IQ SN60WF IOLs (Alcon, Fort Worth, USA) were tested for their resistance to glistenings formation. All IOLs had the same refractive power of +21.0 dioptres. The Eyecryl Plus ASHFY600 IOL and AcrySof IQ SN60WF are both single-piece IOLs, made from a hydrophobic acrylic material ( Table 1)..

Accelerated Aging
Microvacuoles (glistenings) were induced in-vitro by temperature changes using an established accelerated aging protocol as previously described in our earlier studies. [8,10] In short, the lenses were hydrated in Sodium Chloride solution (0.9%) in glass flasks and stored in an oven at 45°C for 24 hours. After removal from the oven, the temperature was reduced to 37°C by immersing the flasks in a water-bath. The lenses were kept at 37°C for 2.5 hours.

Evaluation of Glistenings
All samples were examined under an EMZ-8TR Trinocular Zoom Stereo microscope (Meiji Techno, Saitama, Japan). Microscopic images of all IOLs were taken immediately after aging process using an Infinity-2CB digital camera (Lumenera, Nepean, Canada) ( Figure   1).. After placing a grid behind the IOL that separates the lens optic into five standardized rectangular sections, an overview image in 14-fold magnification was obtained for the whole optic ( Figure 2).. Using 90-fold magnification, an image was made for each section: the central section and four peripheral sections: to evaluate the number of glistenings in each section.
Image analysis was performed using the ImageJ software 1.49v. A Prior to image analysis irregular optical fluctuations have been removed by a smoothing procedure using a nonlinear median filter. Contrast and brightness were optimized using the same settings for each IOL ( Figure 3A).. A threshold technique was used in with a defined threshold value to separate image information in a binary image -to distinguish glistenings from the background. The software automatically counted the number of glistenings ( Figure 3B)..

Data analysis
The number of MVs/mm² in the central part and from all five sections was averaged for ten IOLs from each group and given as mean (±standard deviation). Statistical analysis was performed using Excel V.14.7.7 (Microsoft Corporation, Redmond, USA) performing student's t-tests. A P-value less than 0.05 was considered statistically significant.

Material purity
Images of the central part of the lens in 90-fold magnification show only a few glistenings in the Eyecryl Plus ASHFY600 with low variability between all ten Eyecryl IOLs. A larger number of glistenings was observed in the AcrySof IQ SN60WF IOLs (Figure 4).. Software image analysis revealed that the number of microvacuoles per square millimetre was highest in the central part of the AcrySof IQ SN60WF IOL with 41.84 (±27.67) MVs/mm². The lowest amount of glistenings was obtained averaging the five sections of the Eyecryl Plus ASHFY600, with 0.52 (±0.24) MVs/mm². For the AcrySof IOLs the glistenings number in the central part was higher compared to the value of all 5 sections (p < 0.05), for the ASHFY600 both values were very similar, without a statistically significant difference (p = 0.32) ( Table 2)..

Miyata Grading
All of the Eyecryl Plus ASHFY600 IOLs were classified as Miyata Grade 0. Three of ten AcrySof IQ SN60WF IOLs reached Miyata grade 1 but none of them scored Miyata grade 2 ( Figure 5)..

Discussion
The Eyecryl ASHFY600 IOL showed high resistance to glistenings formation using an established laboratory accelerated aging model. Furthermore, compared to the wellestablished AcrySof SN60WF, the ASHFY600 had a lower mean glistenings grade. In general, glistenings numbers were higher in the central part of the lens compared to the periphery in the AcrySof IOLs, corresponding to the lens thickness, which is highest in centre of the IOL optic. Due to the overall low number of glistenings in the ASHFY600 IOLs, mean values for the central section and the periphery did not differ significantly (0.7 and 0.5, respectively).
In general, hydrophobic acrylate has some advantages over other IOL materials. Lenses made of hydrophobic acrylate show a lower tendency to develop posterior capsule opacification in comparison to those made of PMMA or hydrophilic acrylate. [11] Complications associated with hydrophilic acrylate lenses like IOL calcification have not been described in hydrophobic IOL material. [12] Hydrophobic acrylate IOLs can be costeffectively produced and offer good handling during small incision cataract surgery. [4] Despite these benefits, hydrophobic acrylic IOLs are prone to develop glistenings. This long-term change in the material can worsen the lens' optical performance. [8,9]  MVs/mm² suggesting a maintenance of the improved process that leads to the reduced glistenings formation.
The Eyecryl ASHFY600 IOL is made from a hydrophobic acrylate polymer ( Table 1)..
The Eyecryl lens is manufactured by lathe-cutting the polymer which is different to the way Acrysof IOL is made, which is cast-moulding manufactured. Possibly the Eyecryl lens retains a more homogenous copolymer distribution within the final IOL whereas the castmoulding procedure of the Acrysof lens might be rearranging the polymer distribution. In cast-moulding, care must be taken to avoid the development of inhomogeneities that can re-distribute co-polymers, chances which would make the lens susceptible to further material changes such as microvacuole formation. [14] In a comparative clinical study, Nishihara et al found that lathe-cut lenses show better long-term stability (regarding surface light-scattering) compared to cast-moulded lenses. [14] After shaping the lens by lathe-cutting or cast-moulding, a subsequent step in manufacturing usually includes a polishing process. This stage has been shown to be the potential cause of postoperative material changes in hydrophilic acrylic lenses from a series of lenses affected by opacification, the residual polishing materials, like Aluminium Oxide, might have remained on the lens surface and provoking the postoperative clouding of the lenses. [15] Thus, the IOL production process as well as the polymer are crucial elements in providing a lens with a resistance to material changes. Our results suggest that lathe-cutting a lens is superior to cast-moulding and we consider the new technologies, such as laser-cutting the lens, might further improve IOL manufacturing.
Another approach to reduce the tendency for glistenings formation is to improve the polymer by introducing hydrophobic IOL polymer compositions that have increased hygroscopy. Hygroscopy describes a material's ability to absorb and hold water inside the material. Water entering the material connects with the hydrophilic groups, thus avoiding water accumulation in vacuoles or pockets and forming glistenings. [4] The more hygroscopic a material is, the higher its equilibrium water content (EWC) under certain environmental conditions. Apart from the composition of the material, the EWC depends on the concentration of salts in its surrounding solution and the environmental temperature. Early hydrophobic materials for IOLs had low hygroscopy: the AcrySof material introduced in the 1990s has an EWC as low as 0.1-0.5%. [16] Some of the new generation hydrophobic materials incorporate a certain amount of acrylate with hydrophilic groups, thus leading to equilibrium water contents around 4% to 5 %. [4] Only a few companies disclose the exact copolymer composition used for their IOLs. One known composition is that of the enVista IOL made by Bausch & Lomb (New York, USA). Its copolymer consists of 3 different monomers: poly(ethylene glycol) phenyl ether acrylate (40%), 2-hydroxyethyl methacrylate (HEMA, 30%) and styrene (26%), cross-linked by ethylene glycol dimethacrylate (4%) -collectively called PHS copolymer. Due to the hydrophilic groups of the HEMA the material has a higher EWC of about 4% and shows a low tendency towards formation of glistenings. [4] Another new generation hydrophobic polymer formulation by PhysIOL (Liège -Belgium) also contains an (undisclosed) amount of a hydrophilic monomer to provide an equilibrium water content of 4.9%, again this offers a low tendency for glistenings formation. [17] As described above, even though improvements in the Acrysof material between 2003 and 2012 led to an increasing resistance to glistenings formation, one can still induce glistenings in these lenses. [1] Glistenings -even a low number of them is considered undesirable, and the Alcon company recently introduced a new material, named Clareon, that is considered to show minimal tendency towards glistenings formation. The company does not disclose its exact material composition; Clareon's EWC is around 1.5%. Several other IOL manufactures that have now addressed the problem of glistenings in their hydrophobic acrylic intraocular IOL materials: Vivinex (Hoya, Singapore), Tecnis (Johnson&Johnson, New Jersey, USA) and RayOne (Rayner, Hove, UK). In our laboratory, invitro accelerated aging studies have confirmed that lenses made of these materials and the Eyecryl ASHFY600 IOL are "glistenings free". However, long-term clinical studies on these new generation hydrophobic IOL materials should be made, to confirm the lower amount of glistenings in IOLs made of advanced hydrophobic materials.

Conclusion
The new Eyecryl ASHFY600 IOL has low tendency towards glistenings formation.