Glistenings: the physiological perspective and the effects of temperature
Barbara K Pierscionek1, Andrzej Grzybowski2, 3
- Faculty of Science , Engineering and Computing, Kingston University London, Penrhyn Road, Kingston-upon-Thames, KT1 2EE, UK
- Department of Ophthalmology, Poznan City Hospital, ul. Szwajcarska 3, 61-285 Poznań, Poland; 2
- Department of Ophthalmology, University of Warmia and Mazury, ul. Żołnierska 14C, Olsztyn, Poland;
The incidence of chronic age-related conditions is increasing concomitant with a rise in the average age of the population. A substantial number of these conditions are protein folding diseases: diabetes, Alzheimer’s disease and cataract amongst the most common. Whilst systemic diseases like the former two are treated in such a way as to stabilise, retard progression and manage symptoms, cataract is considered to be treatable in so far as the opacified lens can be removed and replaced with an artificial implant. The growth of cells and protein synthesis on the posterior capsule, causing light scatter and visual detriment, led to use of materials such as hydrophobic acrylics that were supposed to alleviate the problem of cell growth.
However, the use of hydrophobic acrylic lenses has not been without adverse reaction. Fluid-filled microvacuoles, referred to as glistenings because of their clinical appearance, have been reported in many studies and largely in hydrophobic acrylic implants but also, to lesser degrees, in implants made from other materials1.
In addition to the material of the implant, the production processes and how it is packaged have all been implicated as causal in the formation of microvacuoles. Lathe cut implants are said to have shown fewer glistenings than mold-cast implants 1,2; AcryPak packaging produced more glistenings than Wagon Wheel packaging with the latter showing no glistenings if temperature was maintained at constant level3. These studies whilst highly informative were conducted in vitro. However, the microenvironment of an implant lens in the eye is very difficult to recreate in a laboratory.
Within a living eye, the physiological systems are dynamic and not always predictable. Factors that can cause micro-environmental changes include temperature, patient age, presence of disease, medications and intraocular pressure. Effects can be short-lived or prolonged and responses can be immediate or delayed.
The intraocular lens (IOL), located within the capsular bag, is bathed by the aqueous humour. Proteomic analysis has shown that human aqueous, collected during cataract surgery, contains up to 676 proteins of which 328 are cytokines and receptors4. These cell signalling molecules, the surgical procedure and IOL itself can influence the biology of the capsule. Wound-healing responses leading to lens epithelial cell (LEC) proliferation, migration, epithelial-to-mesenchymal transition (EMT), collagen deposition and lens fibre regeneration resulting posterior capsule opacification (PCO) are examples of the effects on capsular biology5. Although the pathogenesis of PCO is still not clear, it was found that IOL material and design can affect the rate of PCO5.
The one variable which has a fundamental impact on living systems and which is often the manifestation of a disease process, metabolic reaction or response to the environment is temperature. Comparatively few studies have considered the temperature of the eye and the effect of this on the microenvironment. Classical studies6-8 have shown that temperature increases from the cornea to the lens reaching body temperature at the posterior surface of the lens. For ambient temperatures of 23ºC and 33ºC the anterior surface of the lens is just over 26ºC and around 34ºC respectively8. Hence, the bulk of the lens is affected by external temperature and higher the ambient temperature the less steep is the gradient across the lens.
Laboratory studies that have investigated temperature changes close to the physiological range9-11 have shown that the greater the temperature decrease, the greater the likelihood of microvacuole formation.
Water absorption increases in hydrophobic acrylic lenses as the temperature increases1. This becomes pronounced above the glass transition temperature which at around 22ºC for hydrophobic acrylic1,12 is between that of PMMA (Tg around 113 to 118ºC) and silicone (-92 to -119ºC)13.
Given that the point of transition in the capacity to imbibe water occurs at room temperature for hydrophobic acrylics and that the position of an implant is close to that of the anterior lens surface, and therefore within an environment that is close to room temperature, a hydrophobic acrylic implant will be susceptible to water sorption in ambient temperatures. This raises interesting possibilities for minimising the presence of glistenings by controlling external temperature and/or temperature of the eye. This opens up a myriad of new research areas but one needs to be pragmatic and avoid onerous restrictions on daily life. A study that could be done with little imposition would be to investigate whether glistenings can be correlated to location of the IOL and to ocular biometry. Since anterior chamber depth varies amongst individuals, it could be speculated that IOLs situated further from the cornea, where the temperature is higher, may be more vulnerable to the microvacuole formation.
What is needed is more in vivo research in this area with greater consideration given to environmental conditions within which the individual with an implant, particularly one of the hydrophobic acrylic type, finds themselves. An epidemiological study comparing glistenings in different countries with varying climatic conditions, or taking into account the month and season that an implant was inserted would provide valuable insights into the effect of temperature on glistening formation. In vitro studies have the benefit of allowing measurements that cannot be conducted within the eye but are limited if conditions are not within physiological ranges. As far as possible, natural conditions should be replicated, remembering that, with respect to temperature, it should not be taken as body temperature but closer to what is found in the external environment.
The future holds the prospect for much interesting and insightful research that, it is hoped, will not only lead to improved implant designs and materials but will also provide an enhanced understanding of ocular physiology.References
- Werner L. Glistenings and surface light scattering in intraocular lenses. J Catarct Refract Surg 2010;.36: 1398-1420
- Nishihara H. Kageyama T, Ohnishi T, Koike M, Imai M, Shibuya A, Yaguchi S. Glistenings in lathe-cut acrylic intraocular lens [Japanese] Ganka Shijutsu 2000; 13:227-230
- Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysus of AcrySof intraocular lens glistenings in AcryPak and Wagon Wheel packaging. J Cataract Refract Surg 1998; 24: 107-113
- Chowdhury UR, Madden BJ, Charlesworth, MC, Fautsch MP. Proteome analysis of human aqueous humor. Invest. Ophthalmol and Vis Science, 2010; 51: 4921-4931
- Awasthi N. Guo S., Wagner BJ. Posterior Capsular Opacification. Arch Ophthalmol 2009; 12&: 555-562. Werner L. Glistenings and surface light scattering in intraocular lenses. J Cataract Refract Surg 2010; 36: 1398-1420
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- Kato K, Nishida M, Yamane H, Nakamae K, Tagami Y, Tetsumoto K. Glistening formation in an AcrySof lens initiated by spinodal decomposition of the polymer network by temperature change. J Cataract Refract Surg 2001; 27: 1493-1498
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- Tjia, KF. The Science behind hydrophobic acrylic lens materials. Cataract and Refractive Surgery Today March 2011; 34-36
- Tehrani M, Dick HB, Wolters B, Pakula T, Wolf E. Material properties of various intraocular lenses in an experimental study. Ophthalmologica. 2004; 218:57-63