Pseudoexfoliation syndrome

From Wikipedia, the free encyclopedia - View original article

Pseudoexfoliation syndrome
Classification and external resources
ICD-10H40.1
OMIM177650
eMedicinearticle/1206366
 
Jump to: navigation, search
This article is about the eye ailment. For the plastic-based plumbing pipe, see PEX.
Pseudoexfoliation syndrome
Classification and external resources
ICD-10H40.1
OMIM177650
eMedicinearticle/1206366

Pseudoexfoliation syndrome (other names: Exfoliation glaucoma, Pseudoexfoliation glaucoma, Pseudoexfoliation of the lens, Exfoliation syndrome), sometimes abbreviated as PEX,[1] is an aging–related systemic disease manifesting itself primarily in the eyes which is characterized by the accumulation of microscopic granular amyloid-like protein fibers.[2] Its cause is unknown, although there is speculation that there may be a genetic basis. It is more prevalent in women than men, and in persons past the age of seventy. Its prevalence in different human populations varies; for example, it is prevalent in Scandinavia.[2] The buildup of protein clumps can block normal drainage of the eye fluid called the aqueous humor and can cause, in turn, a buildup of pressure leading to glaucoma and loss of vision.[3] As worldwide populations become older because of shifts in demography, PEX may become a matter of greater concern.[4]

History[edit]

Dr. Lindberg in 1917 built his own slit lamp to study pseudoexfoliation syndrome. A slit lamp in an ophthalmology clinic in recent times.

Pseudoexfoliation syndrome (PEX) was first described by an ophthalmologist from Finland named John Lindberg in 1917.[4][5] He built his own slit lamp to study the condition and reported "grey flakes on the lens capsule", as well as glaucoma in 50% of the eyes, and an "increasing prevalence of the condition with age."[6] Several decades later, an ocular pathologist named Georgiana Dvorak-Theobald suggested the term pseudoexfoliation to distinguish it from a similar ailment which sometimes affected glassblowers called true exfoliation syndrome. The latter ailment is caused by heat or "infrared-related changes in the anterior lens capsule" and is characterized by "lamellar delamination of the lens capsule."[4] Sometimes the two terms "pseudoexfoliation" and "true exfoliation" are used interchangeably[6] but the more precise usage is to treat each case separately.

Symptoms[edit]

Patients may have no specific symptoms.[4] In some cases, patients may complain of lessened visual acuity or changes in their perceived visual field, and such changes may be secondary to or different from symptoms normally associated with cataracts or glaucoma.[4]

PEX is characterized by tiny microscopic white[5] or grey[6] granular flakes[4] which are clumps of proteins within the eye which look somewhat like dandruff when seen through a microscope and which are released by cells.[7] The abnormal[8] flakes, sometimes compared to amyloid-like material,[2][4] are visible during an examination of the lens of an eye by an ophthalmologist or optometrist, which is the usual diagnosis.[7] The white fluffy material is seen in many tissues both ocular and extraocular:[8] in the anterior chamber structures,[4][5] trabecular meshwork, central disc, zonular fibres, anterior hyaloid membrane, pupillary and anterior iris, trabecula, and occasionally the cornea.[9][10] The flakes are widespread.[8] One report suggested that the granular flakes were from abnormalities of the basement membrane in epithelial cells, and that they were distributed widely throughout the body and not just within structures of the eye.[4] There is some research suggesting that the material may be produced in the iris pigment epithelium, ciliary epithelium, or the peripheral anterior lens epithelium.[4] A similar report suggests that the proteins come from the lens, iris, and other parts of the eye.[3] A report in 2010 found indications of an abnormal ocular surface in PEX patients, discovered by an eye staining method known as rose bengal.[11]

Diagram of the eye. a = optic nerve; b = optic disc; c = sclera; d = choroid; e = retina; f = zonular fibres; g = posterior chamber; h = iris; i = pupil; j = cornea; k = anterior chamber (filled with aqueous humour); l = ciliary muscle; m = lens; n = suspensory ligament; o = vitreous humour; p = fovea

PEX can become problematic when the flakes become enmeshed in a "spongy area" known as the trabecular meshwork and block its normal functioning,[2] and may interact with degenerative changes in the Schlemm's canal and the juxtacanalicular area.[4] The blockage leads to greater-than-normal elevated intraocular pressure[2] which, in turn, can damage the optic nerve.[7] The eye produces a clear fluid called the aqueous humor which subsequently drains such that there is a constant level of safe pressure within the eye, but glaucoma can result if this normal outflow of fluid is blocked.[7] Glaucoma is an umbrella term indicating ailments which damage the neural cable from the eye to the brain called the optic nerve, and which can lead to a loss of vision.[7] In most cases of glaucoma, typically called primary open-angle glaucoma, the outflow does not happen normally but doctors can not see what is causing the blockage; with PEX, however, the flakes are believed to be a cause of the blockage.[7] PEX flakes by themselves do not directly cause glaucoma, but can cause glaucoma indirectly by blocking the outflow of aqueous humor, which leads to higher intraocular pressure, and this can cause glaucoma.[4] PEX has been known to cause a weakening of structures within the eye which help hold the eye's lens in place, called lens zonules.[2]

Diagnosis[edit]

PEX is usually diagnosed by an eye doctor who examines the eye using a microscope. The method is termed slit lamp examination and it is done with an "85% sensitivity rate and a 100% specificity rate."[4] Since the symptom of increased pressure within the eye is generally painless until the condition becomes rather advanced, it is possible for people afflicted with glaucoma to be in danger yet not be aware of it.[7] As a result, it is recommended that persons have regular eye examinations to have their levels of intraocular pressure measured, so that treatments can be prescribed before there is any serious damage to the optic nerve and subsequent loss of vision.[7]

Causes[edit]

The cause or etiology of pseudoexfoliation glaucoma is generally unknown.[2][4][7]

PEX is generally believed to be a systemic disorder,[2][4][6] possibly of the basement membrane of the eye.[2] Researchers have noticed deposits of PEX material in various parts of the body, including in the skin, heart, lungs, liver, kidneys, and elsewhere.[6] Nevertheless, what is puzzling is that PEX tends to happen in only one eye first, which scientists call unilaterality,[2] and in some cases, gradually afflicts the other eye, which is termed bilaterality.[4][9] According to this reasoning, if PEX were a systemic disorder, then both eyes should be affected at the same time, but they are not.[9] There are contrasting reports about the extent and speed with which PEX moves from one eye to both eyes. According to one report, PEX develops in the second eye in 40% of cases.[4] A contrasting report was that PEX can be found in both eyes in almost all situations if an electron microscope is used to examine the second eye, or if a biopsy of the conjunctiva was done, but that the extent of PEX is the second eye was much less than the first one.[4] A different report suggested that two thirds of PEX patients had flakes in only one eye.[9][12] In one long term study, patients with PEX in only one eye were studied, and it was found that over time, 13% progressed to having both eyes afflicted by PEX.[9] Scientists believe that elevated levels of plasma homocysteine are a risk factor for cardiovascular disease,[4] and two studies have found higher levels of plasma homocysteine in PEX patients,[13] or elevated homocysteine concentrations in tear fluids produced by the eye.[14]

There is speculation that PEX may be caused by oxidative damage and the presence of free radicals, although the exact nature of how this might happen is still under study.[4] Studies of PEX patients have found a decrease in the concentrations of ascorbic acid,[15] increase in concentrations of malondialdehyde,[16] and an increase in concentrations of 8-iso-prostaglandinF2a.[17]

There is speculation that genetics may play a role in PEX.[4][6] A predisposition to develop PEX later in life may be an inherited characteristic, according to one account.[4] One report suggested the genetic component was "strong".[1] One study performed in Iceland and Sweden has associated PEX with polymorphisms in gene LOXL1.[5] A report suggested that a specific gene named LOXL1 which was a member of the family of enzymes which play a role in the linking of collagen and elastin inside cells. LOXL1 was responsible for "all the heritability" of PEX, according to one source.[6] Two distinct mutations in which a single nucleotide was changed, or called a single nucleotide polymorphism or SNP, was discovered in Scandinavian populations and confirmed in other populations, and may be involved with the onset of PEX.[6]

The gene is called LOXL1 ... Because pseudoexfoliation syndrome is associated with abnormalities of the extracellular matrix and the basement membrane, this gene could reasonably play a role in the pathophysiology of the condition.

—Dr. Allingham[6]

Researchers are investigating whether factors such as exposure to ultraviolet light, living in northern latitudes, or altitude influence the onset of PEX.[4] One report suggested that climate was not a factor related to PEX.[4] Another report suggested a possible link to sunlight as well as a possible autoimmune response, or possibly a virus.[1]

Prevalence[edit]

Scientists are studying different populations and relationships to try to learn more about the disease. They have found associations with different groups but it is not yet clear what the underlying factors are and how they affect different peoples around the world.

PEX is more prevalent in regions such as Scandinavia but it is not clearly understood why this is the case. In picture: a scene from western Norway.

Treatment[edit]

Conventional surgery to treat glaucoma makes a new opening in the meshwork. This new opening helps fluid to leave the eye and lowers intraocular pressure.

While PEX itself is untreatable as of 2011, it is possible for doctors to minimize the damage to vision and to the optic nerves by the same medical techniques used to prevent glaucoma.

In a surgical procedure called trabectome, the trabecular meshwork is removed to help glaucoma patients.

Patients should continue to have regular eye examinations so that physicians can monitor pressure levels and check whether medicines are working.

Research[edit]

Scientists and doctors are actively exploring how PEX happens, its causes, and how it might be prevented or mitigated. Research activity to explore what causes glaucoma has been characterized as "intense".[7] There has been research into the genetic basis of PEX. One researcher speculated about a possible "two-hit hypothesis" in which a single mutation in the LOXL1 gene puts people at risk for PEX, but that a second still-to-be-found mutation has some effect on the proteins, possibly affecting bonds between chemicals, such that the proteins are more likely to clump together and disrupt the outflow of aqueous humor.[6]

Alternative names[edit]

References[edit]

  1. ^ a b c "Glaucoma In-Depth Report". The New York Times. 2011-07-09. Retrieved 2011-07-09. "Pseudoexfoliation (PEX) syndrome ... The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk." 
  2. ^ a b c d e f g h i j k l m n o p Yichieh Shiuey, MD (March 26, 1997). "Glaucoma Quiz 1". Digital Journal of Ophthalmology. Retrieved 2011-08-21. "... In Scandinavia, this condition represents greater than 50% of all cases of open angle glaucoma." 
  3. ^ a b c "Glaucoma". The New York Times. 2011-08-19. Retrieved 2011-08-19. "... Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. The substance is composed of proteins produced by the lens, iris, and other parts of the eye." 
  4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag Mauricio E Pons, MD; Chief Editor: Hampton Roy Sr, MD; contributing authors: Babak Eliassi-Rad, MD; Bradford Shingleton, MD; Simon K Law, MD, PharmD (Aug 4, 2011). "Pseudoexfoliation Glaucoma". Medscape. Retrieved 2011-08-15. 
  5. ^ a b c d e Damji, Karim F. (October 2007). "Progress in understanding pseudoexfoliation syndrome and pseudoexfoliation-associated glaucoma". Canadian Journal of Ophthalmology 42 (5): 657–658. doi:10.3129/I07-158. PMID 17891191. Retrieved 2009-04-19. 
  6. ^ a b c d e f g h i j k Tony Realini, M.D. "A new gene for pseudoexfoliation". EyeWorld. Retrieved 2011-08-05. "A new gene defect has been found that accounts for essentially all the heritability of pseudoexfoliation syndrome." 
  7. ^ a b c d e f g h i j k l m n o p q Arthur J. Sit, MD, ophthalmology, Mayo Clinic, Rochester, Minn. (April 23, 2006). "Many types of glaucoma, one kind of damage to optic nerve". Chicago Tribune. Retrieved 2011-08-15. "Glaucoma ... Because elevated intraocular pressure (IOP) is the most important risk factor for glaucoma, most treatments are directed at lowering this pressure." 
  8. ^ a b c N Demir, T Ulus, O E Yucel, E T Kumral, E Singar and H I Tanboga (June 24, 2011). "Assessment of myocardial ischaemia using tissue Doppler imaging in pseudoexfoliation syndrome". doi:10.1038/eye.2011.145. Retrieved 2011-08-15. 
  9. ^ a b c d e M Citirik, G Acaroglu, C Batman, L Yildiran and O Zilelioglu. "A possible link between the pseudoexfoliation syndrome and coronary artery disease" 21 (1). doi:10.1038/sj.eye.6702177. Retrieved 2011-08-15. 
  10. ^ Mizuno K, Murois S (1979). "Cycloscopy of pseudoexfoliation". Am J Ophthalmol 87 (4): 513. PMID 443315. 
  11. ^ "Data from E. Viso and colleagues advance knowledge in exfoliation syndrome epidemiology." Biotech Week. NewsRX. 2010. 12 Sep. 2012, Highbeam Research article Quote=An abnormal ocular surface detected by rose bengal staining is highly prevalent among subjects with pseudoexfoliation.
  12. ^ Henry JC, Kruptin T, Schmitt M, Lauffer J, Miller E, Ewing MQ et al. (1987). "Long-term follow-up of pseudoexfoliation and the development of elevated intraocular pressure". Ophthalmology 94 (5): 545–552. doi:10.1016/s0161-6420(87)33413-x. PMID 3601370. 
  13. ^ Vessani RM, Ritch R, Liebmann JM, Jofe M (2003). "Plasma homocysteine is elevated in patients with exfoliation syndrome". Am J Ophthalmol 136 (1): 41–6. doi:10.1016/s0002-9394(03)00077-1. PMID 12834668. 
  14. ^ Roedl JB, Bleich S, Reulbach U, Rejdak R, Kornhuber J, Kruse FE et al. (2007). "Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma". J Glaucoma 16 (2): 234–9. doi:10.1097/IJG.0b013e31802d6942. PMID 17473737. 
  15. ^ Koliakos GG, Konstas AG, Schlotzer-Schrehardt U, Bufidis T, Georgiadis N, Ringvold A (December 2002). "Ascorbic acid concentration is reduced in the aqueous humor of patients with exfoliation syndrome". Am J Ophthalmol 134 (6): 879–83. doi:10.1016/s0002-9394(02)01797-x. PMID 12470757. 
  16. ^ Yimaz A, Adiguzel U, Tamer L, Yildirim O, Oz O, Vatansever H (February 2005). "Serum oxidant/antioxidant balance in exfoliation syndrome". Clin Experiment Ophthalmol 33 (1): 63–6. doi:10.1111/j.1442-9071.2005.00944.x. PMID 15670081. 
  17. ^ Koliakos GG, Konstas AG, Schlötzer-Schrehardt U, Hollo G, Katsimbris IE, Georgiadis N. "8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome". Br J Ophthalmol 87 (3): 353–6. doi:10.1136/bjo.87.3.353. 
  18. ^ Roth M, Epstein DL (1980). "Exfoliation syndrome". Am J Ophthalmol 89 (4): 477–81. PMID 7369310. 
  19. ^ Cashwell LF Jr, Shields MB (1988). "Exfoliation syndrome in the southeastern United States. I. Prevalence in open-angle glaucoma and non-glaucoma populations". Acta Ophthalmol Suppl 184: 99–102. PMID 2853929. 
  20. ^ "Greek population has higher prevalence of pseudoexfoliation". BioPortfolio. April 15, 2011. Retrieved 2011-08-15. "Pseudoexfoliation was found to be more prevalent in Greece than in other white populations," 
  21. ^ Karger RA, Jeng SM, Johnson DH, Hodge DO, Good MS (2003). "Estimated incidence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Olmsted County, Minnesota". J Glaucoma 12 (3): 193–7. doi:10.1097/00061198-200306000-00002. PMID 12782834. 
  22. ^ Summanen P, Tönjum AM (1988). "Exfoliation syndrome among Saudis". Acta Ophthalmol Suppl 184: 107–11. PMID 2853905. 
  23. ^ Bialasiewicz AA, Wali U, Shenoy R, Al-Saeidi R (2005). "Patients with secondary open-angle glaucoma in pseudoexfoliation (PEX) syndrome among a population with high prevalence of PEX. Clinical findings and morphological and surgical characteristics". Ophthalmologe 102 (11): 1064–8. doi:10.1007/s00347-005-1226-2. PMID 15871021. 
  24. ^ Bartholomew RS (1973). "Pseudocapsular exfoliation in the Bantu of South Africa. II. Occurrence and prevalence". Br J Ophthalmol 57 (1): 41–5. doi:10.1136/bjo.57.1.41. PMC 1214820. PMID 4705496. 
  25. ^ Kozart DM, Yanoff M (1982). "Intraocular pressure status in 100 consecutive patients with exfoliation syndrome". Ophthalmology 89 (3): 214–8. doi:10.1016/s0161-6420(82)34804-6. PMID 7088504. 
  26. ^ Aasved H (1971). "Mass screening for fibrillopathia epitheliocapsularis, so-called senile exfoliation or pseudoexfoliation of the anterior lens capsule". Acta Ophthalmol (Copenh). 49 (2): 334–43. doi:10.1111/j.1755-3768.1971.tb00958.x. PMID 5109796. 
  27. ^ Shrum KR, Hattenhauer MG, Hodge D (2000). "Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation". Am J Ophthalmol 129 (1): 83–6. doi:10.1016/S0002-9394(99)00255-X. PMID 10653417. 
  28. ^ a b Rich Daly. "Pseudoexfoliation syndrome’s surgical challenge". EyeWorld. Retrieved 2011-08-21. "... Dr. Crandall urges surgeons to probe for such changes early because it is surgically much easier to repair the phacodonesis before the lenses have dropped."