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Hemodynamic evaluation of the posterior ciliary circulation in exfoliation syndrome and exfoliation glaucoma.

BACKGROUND: Previous studies have reported impaired blood flow in the ophthalmic artery (OA) and central retinal artery (CRA) in exfoliation syndrome and exfoliation glaucoma. This study evaluates blood flow at the long and short posterior ciliary arteries (LPCA and SPCA, respectively) in these conditions. METHODS: Consecutively examined candidates for cataract surgery were included. Only one eye (OD) was included in the analyses for consistency. Patients were classified into non-glaucoma and non-exfoliation (controls), primary open angle glaucoma (POAG), exfoliation syndrome and exfoliation glaucoma groups, based on the findings of the OD. Sixty-eight patients (41 males, 60.3%) were included. Color Doppler imaging (CDI) of the nasal and temporal branches of LPCA and SPCA was performed using a 7.5 Mhz probe. The peak systolic velocity (PSV), end diastolic velocity (EDV) and resistivity index (RI) were recorded for the examined vessels. RESULTS: EDV at the LPCA was significantly lower in exfoliation syndrome and glaucoma, compared with controls and POAG respectively. EDV was significantly lower and RI was significantly higher at the SPCA in exfoliation glaucoma, compared with exfoliation, whereas respective differences were statistically not significant between controls and POAG. CONCLUSIONS: The hemodynamic impairment at the LPCA in exfoliation syndrome and glaucoma supports an association between exfoliation and ischemic stress at the anterior ocular segment.

Blood Circulation↗

Exfoliation syndrome.

Exfoliation syndrome (XFS) is an age-related disorder of the extracellular matrix characterized by production and progressive accumulation of small, white deposits of a fibrillar extracellular material in many ocular tissues, most commonly seen on the pupillary border and anterior lens capsule. Characteristic signs of pigment liberation and deposition throughout the anterior segment aid in the diagnosis. Exfoliation syndrome predisposes to both open-angle and angle-closure glaucoma, and to capsular rupture, zonular dehiscence, and vitreous loss during cataract extraction. Exfoliation syndrome is associated with ocular and perhaps systemic ischemia. The exact chemical composition of exfoliation material remains unknown. Medical, laser, and surgical therapy are similar to treatment of primary open-angle glaucoma.

Adrenergic alpha-Agonists↗

[Cataract and the exfoliative syndrome].

Exfoliation syndrome is more frequently in the older age and represents a risk factor for cataract surgery. This paper presents the results of a clinical trial made on 436 patients with troubles of transparency of the lens who were investigate in our clinic during January 1995-January 1997, and in whom, clinic and paraclinic exams have not revealed any associated ocular disease. In 14% of these patients who presented troubles of transparency of the lens were found uni- or bilateral exfoliation. The authors present the treatment applied both in patients in clinical follow-up (50% of patients with exfoliation syndrome develop secondary glaucoma) and patients who underwent surgical treatment. The patients with exfoliation syndrome and cataract have had a high risk to develop intra- and postoperative complications. The surgical treatment suggested by authors is extracapsular cataract extraction, either or without lens implantation and peripheral iridectomy which represents a compulsory step.

Aged↗

Exfoliation syndrome and exfoliation glaucoma.

Exfoliation syndrome abnormal deposition in the anterior segment of the eye of an unknown substance thought to be related to elastic fibres and basement membrane components is associated with accelerated cataract progression. increased frequency of intraoperative and postoperative complications and increased risk for glaucoma and. therefore, is a clinically important finding. A clear association has been shown with age. The syndrome occurs worldwide but its prevalence seems to vary from country to country. The best-known sign of exfoliation syndrome is deposits of greyish-white material on the anterior lens surface. Sometimes exfoliation material can also be seen at the pupillary border, on the anterior iris surface, corneal endothelium, and on the anterior vitreous face. When clinically detected, exfoliation syndrome is somewhat more often unilateral than bilateral. According to recent investigations clinically unilateral exfoliation syndrome is probably never truly unilateral but rather asymmetric, because exfoliation material has been detected ultrastructurally and immunohistochemically around iris blood vessels of the nonexfoliative fellow eyes. Indeed, electron microscopy identifies in various organs of patients with exfoliation syndrome fibrils similar to those seen in intraocular exfoliation deposits. Other clinical signs associated with exfoliation syndrome are pigment dispersion, transillumination defects of the iris and reduced response to mydriatics. In unilateral exfoliation syndrome, intraocular pressure (IOP) of the exfoliative eye is approximately 2 mmHg higher than IOP of the nonexfoliative fellow eye. Whether elevated IOP, vascular changes or exfoliation syndrome itself is the main factor causing optic nerve head damage and conversion of an exfoliative eye to glaucomatous, is not known. Glaucoma in the exfoliation syndrome has been shown to have a more serious clinical course than in primary open-angle glaucoma (POAG). At the time of diagnosis, IOP and its diurnal variation are generally higher and visual field defects tend to be greater in exfoliation glaucoma than in POAG. Because the decrease in lOP variation and lowering of the mean IOP level has been shown to improve visual field prognosis more in exfoliation glaucoma than in POAG, the glaucomatous process is considered to be more pressure-related in exfoliation glaucoma. Furthermore, progression of optic disc damage has been shown to be similar in exfoliation glaucoma and POAG when lOPs are lowered to a comparable level by the treatment. However, vascular disturbances in the posterior segment of the eye might after all be of equal importance in these two types of glaucoma; optic disc haemorrhages and venous occlusions have been reported to be as frequent in exfoliation glaucoma as in POAG. Perhaps in exfoliation glaucoma circullatory disturbances combined with high IOP lead to a particularly relentlessly progressing form of the disease.

Animals↗

The initial stage of the exfoliation syndrome.

Exfoliation of devitalized tissue and pigment from the neuroepithelium of the uveal tract constitute the earliest stage of the exfoliation syndrome according to a biomicroscopic study. With an immuno-histochemical technique exfoliative material from lenses with the classic exfoliation syndrome, demonstrated the same staining characteristics as the pigmentary epithelium of the uvea.

Aged↗

[Lectin electron histochemistry in the skin in patients with exfoliation syndrome].

Exfoliation syndrome has recently been suggested to have a more widespread distribution from the findings of exfoliative-like material outside the globe. To determine whether exfoliative-like material and exfoliative material are identical, they were characterized by electron microscopic lectin histochemistry using sixteen kinds of lectin; PNA, RCA60 and 120, ABA, DBA, SBA, ConA, LCA, WGA, DSA, PHA-E4 and L4, UEA-I, Lotus, MAM and SSA. The staining pattern indicated that sugar residues in these two materials on the trabecular meshwork, lens, and skin have the same characteristics, containing glycoconjugates with sugar residues of beta-galactosyl, alpha-mannosyl, N-acetyl-D-glucosaminyl, and terminal sialic acid.

Aged↗

Why is glaucoma associated with exfoliation syndrome?

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by production and progressive accumulation of a fibrillar material in tissues throughout the anterior segment and also in connective tissue portions of various visceral organs. Mature exfoliation fibrils are composed of 8-10 nm microfibrils resembling elastic microfibrils. The exact chemical composition of exfoliation material (XFM) remains unknown. It appears to consist of a complex glycoprotein/ proteoglycan structure composed of a protein core surrounded by abundant glycoconjugates. The protein components include both non-collagenous basement membrane components and epitopes of the elastic fiber system, particularly components of elastic microfibrils. Overall, XFS is the most common identifiable cause of glaucoma, accounting for the majority of cases in some countries, and causing both open-angle glaucoma and angle-closure glaucoma. Iridolenticular friction leads to loss of XFM from the anterior lens surface and disruption of the iris pigment epithelium, resulting in pigment deposition in the trabecular meshwork, which also produces XFM locally. The primary cause of chronic pressure elevation appears to be the active involvement of trabecular cells and Schlemm's canal cells in particular, in the generalized pathologic matrix process with subsequent degenerative changes of Schlemm's canal and adjacent tissues. Narrow angles and angle-closure are common in XFS. Pupillary block may be caused by a combination of posterior synechiae, increased iris thickness or rigidity, or anterior lens movement secondary to zonular weakness or dialysis. Enlargement of the lens due to cataract formation and relative pupillary constriction are additional factors.

Animals↗

Exfoliation syndrome.

Exfoliation syndrome (XFS) is an age-related disease in which abnormal fibrillar extracellular material is produced and accumulates in many ocular tissues. Its ocular manifestations involve all of the structures of the anterior segment, as well as conjunctiva and orbital structures. Glaucoma occurs more commonly in eyes with XFS than in those without it; in fact, XFS has recently been recognized as the most common identifiable cause of glaucoma. Patients with XFS are also predisposed to develop angle-closure glaucoma, and glaucoma in XFS has a more serious clinical course and worse prognosis than primary open-angle glaucoma. There is increasing evidence for an etiological association of XFS with cataract formation, and possibly with retinal vein occlusion. XFS is now suspected to be a systemic disorder and has been associated preliminarily with transient ischemic attacks, stroke, systemic hypertension, and myocardial infarction. Further ramifications await discovery. Deposits of white material on the anterior lens surface are the most consistent and important diagnostic feature of XFS. The classic pattern consists of three distinct zones that become visible when the pupil is fully dilated. Whereas the classic picture of manifest XFS has been often described, the early stages of beginning exfoliation have not been well defined. Next to the lens, exfoliation material is most prominent at the pupillary border. Pigment loss from the iris sphincter region and its deposition on anterior chamber structures is a hallmark of XFS. Despite extensive research, the exact chemical composition of exfoliation material (XFM) remains unknown. An overproduction and abnormal metabolism of glycosaminoglycans have been suggested as one of the key changes in XFS. The protein components of XFM include both noncollagenous basement membrane components and epitopes of the elastic fiber system such as fibrillium. Regardless of etiology, typical exfoliation fibers have been demonstrated electron microscopically in close association with the pre-equatorial lens epithelium, the nonpigmented ciliary epithelium, the iris pigment epithelium, the corneal endothelium, the trabecular endothelium, and with almost all cell types of the iris stroma, such as fibrocytes, melanocytes, vascular endothelial cells, pericytes, and smooth muscle cells. The presence of XFS should alert the physician to the increased risks of intraocular surgery, most commonly zonular dehiscence, capsular rupture, and vitreous loss during cataract extraction. Heightened awareness of this condition and its associated clinical signs are important in the detection and management of glaucoma, and preoperative determination of those patients at increased risk for surgical complications.

Cataract↗

Current concepts in the pathogenesis and management of exfoliation syndrome and exfoliative glaucoma.

Exfoliative glaucoma is a common, sight-threatening disease that develops as a consequence of exfoliation syndrome. There are important differences in the clinical appearance, course, and prognosis of exfoliative glaucoma versus primary open-angle glaucoma. At the clinical, biochemical, and cellular levels, exfoliative glaucoma is a distinct entity, with an intriguing mechanism of development and numerous systemic manifestations that require further elucidation. The subtlety of clinical signs results in the diagnosis of exfoliative glaucoma often being overlooked and resulting in less-than-ideal management. We provide an overview of recent studies investigating the medical, laser, and surgical therapy of exfoliative glaucoma, with a focus on innovative approaches that may slow the progression of, or even prevent, the development of exfoliation syndrome and exfoliative glaucoma.

Antihypertensive Agents↗

The cornea in exfoliation syndrome.

Exfoliation syndrome (EXS) is a disorder which affects some structures of the eye. We studied the changes of the cornea in patients with EXS and compared with those in normal persons. A prospective study of 96 consecutive patients more than 70 years of age was set up. 48 of them (70 eyes, group A) had exfoliation in one or both eyes and 48 (group B) had no ocular disease other than senile cataract. None of the patients had any systemic disease. The endothelium and thickness of the central cornea were studied. Endothelium of the eyes with EXS showed significantly (p < 0.05) lower cell density than those of group B. Cornea in group A was significantly thicker (p < 0.05) than in group B. The morphology of the endothelium in group A showed a decrease of hexagonal cells and a higher rate of polymegethism compared to group B. Corneal thickness and endothelium showed no significant differences between the eyes with EXS and normal fellow eyes. These results add another risk factor, the fragile cornea, in eyes with EXS, in cataract surgery.

Aged↗

Increased aqueous humor basic fibroblast growth factor and hyaluronan levels in relation to the exfoliation syndrome and exfoliative glaucoma.

PURPOSE: To quantify the concentrations of basic fibroblast growth factor (bFGF) and hyaluronan (HA) in the aqueous humor of patients with the exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). METHODS: Aqueous humor bFGF and HA levels were measured in 13 patients with XFS and in 7 patients with XFG. The results were compared with those obtained from 17 healthy controls. RESULTS: Mean bFGF levels were significantly higher in the XFG patients than those in the XFS patients, which in turn were higher than the bFGF levels in the healthy individuals. Aqueous humor HA levels in both patients with the XFS and the XFG were significantly higher compared to the controls. CONCLUSION: We suggest that bFGF plays an important role in the pathogenesis of XFS and XFG, as well as in the synthesis of secreted HA, which may result in connective tissue degradation that affects the ocular anterior segment.

Aged↗

Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma.

PURPOSE: To study extracellular matrix (ECM) metabolism by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in aqueous humor (AH) samples collected from primary open-angle glaucoma (POAG), exfoliation syndrome (EXS), and exfoliation glaucoma (EXG) in relation to samples derived from cataract control patients. MATERIALS AND METHODS: Seventy-one AH samples were collected during cataract extraction and trabeculectomy. The expression and molecular forms of MMP-2, -8, -9, -13, and -14 and tissue inhibitor of metalloproteinases-1 and -2 (TIMPs) were analyzed by Western immunoblotting. Gelatinase and collagenase activities were studied by zymography and type I collagen degradation assays, respectively. MMP-2 and TIMP-2 concentrations were measured by ELISA assays. RESULTS: By Western immunoblotting all the studied MMPs were mainly in their latent form in all diagnostic groups. Zymography demonstrated that MMP-2 represents the major gelatinase in AH. Similarly, type I collagenolytic activity was low and similar in cataract and glaucoma samples. In ELISA measurements the TIMP-2 levels were significantly elevated in glaucoma and EXS samples in comparison to cataract controls (P < 0.05). CONCLUSION: TIMP-2 is elevated in glaucomatous process over MMP-2, which support and further extend the conjuncture that the ECM accumulation rather than degradation predominates in the pathogenesis of POAG and EXG.

Aged↗

The ultrastructural changes in the exfoliation syndrome.

Exfoliation fibrils have a characteristic ultramicroscopic appearance. They are 20-30 nm thick with 10 nm subunits and may be 800 or 900 nm long. They sometimes have a characteristic banding periodicity of about 50 nm. The fibrils have been located in the lens capsule, zonular threads, iris, ciliary body and trabecular meshwork. Extraocular locations have also been found in conjunctival vessels and retroorbital tissue.

Anterior Eye Segment↗

Exfoliation syndrome.

The exfoliation syndrome has now been recognised all over the world and even in such ethnic groups as the Skolt Lapps, Navajo Indians, Australian aborigines and all major tribes of the South African Bantu. The prevalence appears rather all major tribes of the South African Bantu. The prevalence appears rather similar in those countries where population-based surveys have been conducted. The exfoliation syndrome is age-dependent. In Caucasians the prevalence is low before the age of 60 years, increasing steadily to about 8 per cent in the group aged 80 to 90 years. However, the Bantus show a 6.4 per cent prevalence in the age group 30 to 39 years. In population-corrected surveys the females show a higher prevalence of the syndrome than do the males. Familial occurrence of exfoliation and population genetics have suggested an autosomal dominant mode of heredity. Suggestions of differences in prevalence of the exfoliation syndrome in different countries and even in different areas of the same country call for further population-based even in different areas of the same country call for further population-based surveys. Recognition of exfoliation is clinically of paramount importance as 20 percent of exfoliation patients show abnormalities of intraocular pressure. Poor pupillary dilatation, fragile zonular fibres and 2 per cent lens displacement may induce difficulties in extracapsular cataract surgery with posterior chamber lens implantation. Ciliary sulcus fixation of intraocular lenses with large diameter of the haptics is recommended.

Adult↗

Plasma homocysteine is elevated in patients with exfoliation syndrome.

PURPOSE: To compare plasma homocysteine concentrations among patients with exfoliation syndrome, exfoliative glaucoma, normal-tension glaucoma, and normal control subjects without vascular or inflammatory ocular disease or glaucoma. DESIGN: Cross-sectional study. METHODS: We tested 25 patients with exfoliation syndrome, 50 with exfoliative glaucoma, 25 with normal-tension glaucoma, and 24 control subjects. Fasting plasma homocysteine concentrations were measured by fluorescence polarization immunoassay. Patients using vitamin supplements or medications known to alter serum homocysteine were excluded. RESULTS: Homocysteine levels were higher in both exfoliatin groups compared with controls (exfoliation syndrome: P =.003; exfoliative glaucoma: P =.009); levels in normal-tension glaucoma were higher than but not significantly different from those in controls (P =.2). Hyperhomocysteinemia was present in 16 of 25 (64%) exfoliation syndrome patients, 28 of 50 (56%) exfoliative glaucoma patients, 13 of 25 (52%) normal-tension glaucoma patients, and 7 of 24 (29.2%) controls (P =.005). Multiple logistic regression analyses comparing exfoliation syndrome and exfoliative glaucoma patients with controls indicated that elevated plasma homocysteine concentration was a significant risk factor for exfoliation syndrome, in both those patients (odds ratios per 1.0 micromol/l increase in plasma homocysteine concentrations = 1.47; 95% confidence interval [CI] = 1.08-2.0) and in exfoliative glaucoma patients (odds ratio = 1.3; 95% CI = 1.07-1.6). Although exfoliative glaucoma and normal-tension glaucoma patients were not significantly different with respect to hyperhomocysteinemia, logistic regression modeling of exfoliative glaucoma vs normal-tension glaucoma patients showed that an increased homocysteine concentration was a significant risk factor for exfoliation syndrome in the presence of glaucoma (odds ratio per 1.0 micromol/l increase in homocysteine = 1.2, 95% CI = 1.0-1.4). These relationships were not affected by adjustment for potential confounding due to sex, history of hypertension, or other factors. RESULTS: Elevated plasma homocysteine, a risk factor for cardiovascular disease, is more common in exfoliation syndrome and exfoliative glaucoma patients than healthy controls. Patients with exfoliation syndrome may benefit from measurement of homocysteine levels.

Aged↗

Ultrasound biomicroscopic classification of zonules in exfoliation syndrome.

PURPOSE: Exfoliation changes in the zonules or ciliary processes may be the earliest clinical sign of the exfoliation syndrome (XFS). In the present study we investigated the usefulness of ultrasound biomicroscopy (UBM) for detecting the early changes of XFS in zonules. METHODS: Both eyes of 11 patients with unilateral XFS and the unilateral eyes of 11 subjects without evidence of XFS were examined using UBM. The incidence of zonular changes was compared among the XFS-positive eyes of the patients, their contralateral XFS-negative eyes, and the healthy eyes of the subjects without XFS. RESULTS: Using UBM, we could successfully describe the zonules in all UBM images of all subjects. In the four quadrants, the incidence of granular-type zonules was statistically different among the three groups: it was higher in XFP-positive eyes than in XFS-negative eyes, and it was higher in XFS-negative eyes than in healthy eyes. CONCLUSIONS: UBM can detect the zonular changes that may occur early in XFS. A granular-type change in the zonules may be the most typical finding in the presence of exfoliation material. Diagnostic criteria are proposed for the early detection of XFS, based on the changes found in the zonules by UBM.

Aged↗

Light microscopy of the exfoliation syndrome.

The exfoliation syndrome affects all structures of the ocular anterior segment, as well as the conjunctiva and occasionally, nonocular structures. The exfoliative material has been shown by a series of light microscopic and gross anatomic studies to be only loosely adherent to the anterior lens capsule, zonules and anterior vitreous face, and firmly adherent to the equatorial lens capsule and posterior epithelium of the iris and the nonpigmented ciliary epithelium. Electron microscopy demonstrates that, in these latter regions, exfoliation material consisting of characteristic, cross-banded fibrils embedded in an amorphous matrix, is present both within the epithelial cells and associated with a disorganized, reduplicated basement membrane. These findings suggest that the material arises from the epithelium of the lens, iris and ciliary body, possibly the result of an underlying metabolic disorder. From these areas, the material enters the aqueous humor and later deposits on the anterior lens capsule, zonules, vitreous face, anterior surface of the iris, and trabecular meshwork. Histochemical studies demonstrate the presence of glycosaminoglycans, which may comprise the interfibrillar portion of the exfoliative material. Other studies demonstrate histochemical similarities between exfoliative material and zonules and are supported by recent work suggesting that the exfoliative fibrils are related to the microfibrillar portion of elastin. Although some reports suggest similarities between exfoliative material and amyloid, a majority of histochemical studies do not support this possibility.

Amyloid↗