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Asteroid Hyalosis: PF Kador and M Wyman Pathogenesis and Prospects for Prevention

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Asteroid Hyalosis: PF Kador and M Wyman Pathogenesis and Prospects for Prevention Eye (2008) 22, 1278–1285 & 2008 Macmillan Publishers Limited All rights reserved 0950-222X/08 $32.00 www.nature.com/eye 1,2 3 CAMBRIDGE OPHTHALMOLOGY SYMPOSIUM Asteroid hyalosis: PF Kador and M Wyman pathogenesis and prospects for prevention Abstract the eyeball while providing a clear unobstructed path for light to reach the retina. Asteroid hyalosis (AH) is a common In addition, it hinders the forward diffusion of degenerative process in which fatty calcium oxygen from the retinal blood supply to the globules collect within the vitreous humour. anterior segment of the eye where it can cause The condition rarely causes visual oxidation damage to the lens. The vitreous is an disturbances, and surgical removal is only extracellular matrix that is composed of rarely required. The presence of AH has been collagen fibrils with the carbohydrate polymer associated with systemic diseases such as hyaluronan (hyaluronic acid) serving as the diabetes; however, research in this area has major component between the fibrils.1 With age, been hampered by the lack of an animal model it may partially liquefy as a result of hyaluronan of AH. Recently, we have reported that AH breakdown associated with oxidative stress.2,3 occurs in galactose-fed beagles that develop Once liquefied or surgically removed, the the advanced stages of diabetes-like vitreous does not reform significantly. retinopathy. Comparisons of vitreous humour 1Department of Pharma- Opacities may form in the clear vitreous as a containing asteroid bodies (ABs) collected ceutical Sciences, College of result of developmental abnormalities, injury, or from these galactose-fed beagles and vitreous Pharmacy, University of disease. Developmental opacities present from Nebraska Medical Center, samples from age-matched normal beagles birth are the remnants of the hyaloid system Omaha, NE, USA without ABs indicate that ABs contain calcium that are located in Cloquet’s canal, whereas and phosphorous. Subtraction analysis of 2 degenerative opacities, associated with Department of chloroform extracts of the vitreous samples by Ophthalmology, College of inflammatory debris, often appear after ocular electrospray mass spectroscopy resulted in the Medicine, University of inflammation, ocular haemorrhage, posterior identification of the quasimolecular ion of 1,2- Nebraska Medical Center, vitreous detachment, or vitreous haemorrhage. Omaha, NE, USA dipalmitoyl-glycero-3-phosphoethanolamine Ocular trauma or inflammation may also result (DPPE) as the main component of ABs. Since 3 in the accumulation of glittering cholesterol Department of Veterinary several reports indicate that ABs are composed crystals in the vitreous humour along with the Clinical Sciences, of lipid–calcium complexes, we have proposed Comparative anterior chamber and subretinal space that the main component of ABs in the Ophthalmology, College of (synchisis scintillans). However, the most galactose-fed dogs with AH is a quasimolecular Veterinary Medicine, The common clinically observed degenerative Ohio State University, ion of DPPE in which two molecules of DPPE opacity of the vitreous is asteroid hyalosis (AH). Columbus, OH, USA are complexed through their phosphates Accurately differentiated from synchisis groups with calcium. We suggest that these scintillans in the late 1800s, it was first called Correspondence: PF Kador, lipid components diffuse into the vitreous from College of Pharmacy, asteroid hyalitis; however, the name was the degenerating retinas of these dogs. University of Nebraska changed in the 1960s to AH because of the Eye (2008) 22, 1278–1285; doi:10.1038/eye.2008.35; Medical Center, 986025 absence of inflammatory changes. AH is Nebraska Medical Center, published online 14 March 2008 Omaha, NE 68198-6025, USA characterized by spherical white bodies that move along with the vitreous humour when the Tel: þ 1 402 559 9261; Keywords: vitreous; diabetes; asteroid hyalosis; Fax: þ 1 402 559 9543. eye moves. They are present unilaterally in asteroid bodies; animal models; galactosemic dog E-mail: [email protected] approximately 75% of patients and are more predominant in men than women unilaterally.4–6 Received: 18 January 2008 Although their presence is obvious upon ocular Accepted in revised form: Introduction 18 January 2008 examination and in severe cases make retinal Published online: The vitreous is a highly hydrated gel-like examination difficult, patients are usually 14 March 2008 substance that provides structural support to unaware of AH because the asteroid bodies Asteroid hyalosis PF Kador and M Wyman 1279 (ABs) rarely cause visual disturbances. Surgical removal obtained human AH. However, the small size and of these opacities is usually not required unless AH amounts of ABs available for study, along with their compromises the patient’s vision. strong adherence to vitreous humour, have limited applications to histological and microscopic techniques. Histological studies indicate that unlike the vitreous Pathogenesis of AH humour, ABs readily stain for the presence of lipids Although AH has been associated with several systemic (Sudan black B and oil red 0) and calcium (von Kossa). diseases, the cause(s) and mechanism(s) of AH formation However, ABs do not dissolve in common fat solvents. remain unknown. Three major studies conclude that AH This led Verhoeff21 in the early 1920s to postulate that is primarily associated with ageing. In the Beaver Dam ABs are calcium soaps with calcium primarily bound to Study of Wisconsin where 4952 patients were examined, the fatty acid carboxylate groups. Forty years later, AH was present in 1.2% of the population with Rodman et al22 confirmed that calcium is bound to the prevalence increasing from 0.2% in subjects 43–54 years main acidic lipid components of ABs. However, its of age to 2.9% in those aged 75–86 years.6 AH was behaviour is not consistent with fatty acid calcium salts primarily unilateral and was more prevalent in men. The because the ABs did not dissolve in glacial acetic acid or Australian Blue Mountains Eye Study of 3654 patients 0.8% HCl but did dissolve in methanolic HCl. Moreover, aged 49–97 years confirmed a similar 1% prevalence of two types of AH were observed. In the first, Type I AH, AH.5 In this group, the prevalence of AH also increased the ABs were suspended in and surrounded by vitreous with age from 0% of persons 49–55 years of age to 2.1% of fibrils. The ABs appeared composed of two zones, a large persons aged 75–97 years, and AH was again more inner zone filled with birefringent particles and a thin prevalent in men. A higher, 1.96%, prevalence of AH was cortical rim composed of condensed nonbirefringent observed in the third study from the University of vitreous particles. In the second, Type II AH, the ABs California at Los Angeles (UCLA) autopsy eye database were surrounded by cellular elements and this whole from 1965 to 2000 where 10 801 patients were examined.4 complex was enmeshed with vitreous fibrils or This retrospective study, which demographically inflammatory tissue. The appearance of these two types matched the characteristics of the US population on the of ABs suggest potential differences in their pathogenic 2000 census, also showed an inverse relationship mechanism(s); however, both types have been between AH and posterior vitreous detachment. documented to be present in the same patient.12 Although these three major studies found AH to Moreover, despite the apparent link with inflammatory primarily correlate with ageing, others suggest that AH is tissues, uveitis is not associated with AH. associated with diabetes mellitus (DM),7–16 In the 1970s, analyses of ABs by X-ray microanalyser hypertension,14,17 hypercholesteraemia or lipidemia,7,15,16 revealed that phosphate, in addition to calcium, is or increased serum calcium levels.18,19 Of these, a link to present as a major element.23 This suggests that calcium DM is most often cited; however, this link is also the most is present in ABs in the form of a calcium phosphate controversial. Although AH predominantly occurs complex (apatite) rather than as fatty acid calcium salts. unilaterally,4–6 AH should be bilateral if linked to Electron microscopy revealed the presence of ‘satellite’ systemic diseases such as DM because each eye is equally ABs composed of a number of round particles of equal exposed to hyperglycaemia. Bilateral ‘trends’ of AH have size and in symmetrical arrangement. These particles been suggested among diabetic populations11 and the appeared embedded in a matrix, which merged with the UCLA autopsy study,4 which observed a statistical surrounding vitreous. These observations led March and association between diabetes and bilateral AH before Shoch23 to minimize the lipid character of ABs and to adjusting the data for age and sex. However, in the suggest that ABs may simply be a physicochemical UCLA study, AH was present only in 20 of 780 diabetics. phenomenon or shift of a part of the normal vitreous AH formation in diabetics has been suggested to be from the liquid to a solid phase. In this process, ‘satellite’ secondary to retinal vascular changes.10 The overall asteroids are initially crystallized from ‘seeds’ formed in relationship between DM and AH is further complicated the supersaturated vitreous. These ‘satellites’ then by data suggesting that AH may arrest the process of conglomerate in the solid phase to form the larger, vitreous collapse or contraction in eyes with proliferative experimentally observed ABs. The basic processes diabetic retinopathy.8,20 leading to this hypothetical supersaturated solution were not identified. In contrast to the suggestion that ABs are derived from Structure and composition of ABs the vitreous, which is naturally low in lipids, Streeten24 The structure and composition of ABs is currently reported in 1982 that ABs must be derived from sources unknown. Studies to date have utilized clinically exogenous to the vitreous. This was based on Eye Asteroid hyalosis PF Kador and M Wyman 1280 observations that large quantities of complex lipids and substances.
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