Loss of heterozygosity in pseudoexfoliation syndrome.
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PURPOSE: Pseudoexfoliation (PEX) syndrome is characterized by the accumulation of a material of unknown origin in the anterior structures of the eye. Loss of heterozygosity (LOH) in a genetic locus indicates the presence of a gene located in the same region that could be implicated in the development or the progression of a disease. In this study, the occurrence of LOH in tissues involved in PEX and the possible correlation of LOH incidence with clinical parameters were evaluated. METHODS: Twelve iris specimens, 12 anterior capsule specimens, and respective blood samples were obtained from 17 patients with PEX (13 men), who were undergoing glaucoma and cataract surgery. Sixteen anterior capsule specimens and four iris specimens were obtained from 16 patients without PEX. Polymerase chain reaction was used to amplify 10 highly polymorphic microsatellite markers located on chromosomes 1, 7, 9, and 13. RESULTS: Overall, 83.3% (20/24) of PEX specimens and 94.11% (16/17) of patients with PEX had LOH. The highest incidence of LOH was observed in marker D13S175 (41.6%) followed by D7S478 and D7S479 (37.5%). Only three non-PEX specimens displayed LOH. The number of loci lost was directly related to the altitude of the patients' present residence, but the number lost did not differ significantly between the iris and capsule samples. CONCLUSIONS: The occurrence of LOH in tissues involved in PEX implies a genetic role in PEX pathogenesis at a cellu lar level. The correlation of LOH incidence with the altitude of the patient's residence, could indicate an increased susceptibility to UV radiation of the chromosomal regions examined. (+info)
Combined exfoliation and pigment dispersion: an overlap syndrome.
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PURPOSE: To describe a series of patients with combined pigment dispersion syndrome (PDS) and exfoliation syndrome (XFS) and to introduce a concept, the overlap syndrome, to aid in assessing multiple risk factors for glaucomatous damage. METHODS: A retrospective review of the records of all patients on our database who carried a diagnosis of both PDS/pigmentary glaucoma (PG) and XFS/exfoliative glaucoma (XFG). RESULTS: We identified 26 patients as having both XFS/XFG and PDS/PG. The average age was 64.3 +/- 9.8 years and 19 of 26 were men. All patients had bilateral PDS/PG. Bilateral XFS/XFG was present in 9 of 26 patients, and of the 17 patients with unilateral involvement, the left eye was affected in 13. CONCLUSION: Both XFS and PDS are common. Middle-aged patients with known PDS/PG should be suspected of having the onset of XFS if 1 eye escapes intraocular pressure control. Patients presenting with unilateral XFG may also have signs of PDS/PG, often remitted. We define an overlap syndrome as the appearance of a new co-morbidity for glaucomatous damage in a patient with a pre-existing risk factor, which then changes the course, and prognosis of the disease. This concept should be particularly useful in dealing with secondary and normal-tension glaucoma. (+info)
mRNA in situ hybridization of TIGR/MYOC in human trabecular meshwork.
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PURPOSE: To determine the distribution of mRNA expression of the trabecular meshwork-induced glucocorticoid response protein/myocilin (TIGR/MYOC) in human trabecular meshwork. METHODS: In situ hybridization using a 1.25-kb probe obtained from reverse transcription-polymerase chain reaction of TIGR/MYOC cDNA was performed to determine the location of cell labeling within the different regions of the meshwork. The effect of dexamethasone on the pattern of labeling was studied in organ cultured meshwork. Trabecular meshwork from three sources was studied: enucleated eyes obtained at autopsy, trabeculectomy specimens obtained during filtration surgery, and meshworks from anterior segments in perfusion organ culture. Hybridization was performed on frozen sections, paraffin sections, and sections from JB-4 plastic-embedded tissue. RESULTS: Labeling for TIGR/MYOC mRNA was present in most trabecular cells of the uveal, corneoscleral, and juxtacanalicular regions but only variably present in the endothelial cells of Schlemm's canal. A similar pattern was found in the trabeculectomy specimens from eyes with primary open-angle or pseudoexfoliative glaucoma. Dexamethasone treatment increased the labeling intensity and number of labeled cells in meshwork, and also the number of labeled endothelial cells of Schlemm's canal. Fresh tissue processed within 12 hours postmortem gave more consistent labeling than older tissue, although some label was found up to 48 hours postmortem. Labeling was found in tissue from all three sources, and with all three embedding techniques; JB-4 sections provided the best morphologic resolution. CONCLUSIONS: In situ hybridization reveals that mRNA expression for TIGR/MYOC is present in most cells in all regions of the meshwork but only variably present in the endothelial cells of Schlemm's canal. Dexamethasone treatment increased the number and intensity of labeled cells, and also increased the number of labeled cells in the endothelial lining of Schlemm's canal. (+info)
Combined pars plana lensectomy-vitrectomy with open-loop flexible anterior chamber intraocular lens (AC IOL) implantation for subluxated lenses.
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OBJECTIVES: To review our experience with combined pars plana lensectomy-vitrectomy and open-loop flexible anterior chamber intraocular lens (AC IOL) implantation for managing subluxated crystalline lenses. METHODS: Retrospective review of 36 consecutive eyes (28 patients), all of which had subluxated crystalline lenses, managed by pars plana lensectomy-vitrectomy with insertion of an open-loop flexible AC IOL. The study was performed at the Medical College of Wisconsin, Milwaukee, over an 8-year period. RESULTS: An average preoperative visual acuity of 20/163 (range, 20/25 to hand motions) improved to 20/36 (range, 20/20 to 4/200) with surgery after a mean follow-up of 14 months (range, 1 to 59 months) (P < .001, Student's paired t test). Final visual acuity of 20/40 or better was achieved in 75% of eyes (27/36). Complications included cystoid macular edema (8% [3/36]), pupillary block (6% [2/36]), retinal detachment (3% [1/36]), hyphema (3% [1/36]), wound leak (3% [1/36]), and transient vitreous hemorrhage (3% [1/36]). No persistent ocular hypertension was seen, nor did angle abnormalities or corneal decompensation develop. CONCLUSIONS: Pars plana lensectomy-vitrectomy with AC IOL implantation appears to be an excellent technique for managing subluxated crystalline lenses. It is associated with a significant improvement in visual acuity (P < .001) and avoids many of the complications seen with extraction of a subluxated lens through a limbal wound. Additionally, use of an AC IOL offers a simplified alternative to placement of a ciliary sulcus sutured posterior chamber intraocular lens (PC IOL). (+info)
Scanning laser ophthalmoscopy of the optic nerve head in exfoliation glaucoma and ocular hypertension with exfoliation syndrome.
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AIMS: To study the relation between optic nerve head topography (Heidelberg retina tomograph, HRT) and disc area, visual field index mean defect (MD), and intraocular pressure (IOP), and to see whether change in HRT parameters is associated with change in MD in a prospective follow up. METHODS: 80 consecutive patients (69 patients with exfoliation glaucoma and 11 with ocular hypertension combined with exfoliation syndrome) were examined before IOP reducing intervention and prospectively followed every 6 months for 2 years. RESULTS: At the entry point, multiple regression analysis showed significant linear association between MD and all HRT parameters, when controlling for disc area. Disc area showed significant association with cup area, cup/disc area ratio, rim area, cup volume, and mean RNFL thickness. Six months after intervention IOP had decreased significantly. Reversible changes in cup area, cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, and maximum cup depth were associated with decrease in IOP. During the follow up period from 6 month to 2 years, IOP did not change significantly, and MD was used as a measure of progression of glaucoma. During this period, only cup shape measure among HRT parameters showed significant association with subsequent change in MD. CONCLUSION: Disc area should be taken into account when using HRT to compare patients. Any effect of change in IOP should be also taken into account when using HRT in follow up. Cup shape measure is a promising indicator of progression of glaucomatous damage. (+info)
Pseudoexfoliation syndrome in Icelandic families.
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AIM: To examine the distribution and clinical ophthalmic characteristics of pseudoexfoliation syndrome (pseudoexfoliation) and glaucoma in Icelandic families. METHODS: Icelandic families containing three or more members aged 70 or older with at least one member with pseudoexfoliation were identified. All family members over age 45 were invited to participate. Visual acuity, Goldmann applanation tonometry, gonioscopy, slit lamp examination before and after dilatation, and dilated fundus examination were performed on all available family members. Pertinent data were obtained from medical records, including ophthalmic history and a medical history of cardiovascular disease, cerebrovascular disease, systemic hypertension, and diabetes mellitus. Participants were classified according to affected status for pseudoexfoliation, glaucoma, and age related macular degeneration. RESULTS: Six families were identified who met the criteria for entry into the study. Of 94 family members who were invited to participate 82 were enrolled (87%). Of these 25 (30%) had pseudoexfoliation syndrome, 51 (62%) were unaffected, and six (7%) were suspects. At least one individual with pseudoexfoliation was identified in the second generation of every family. A parent with pseudoexfoliation was identified in all cases either by examination (4/6) or a review of ophthalmic records (2/6). In all cases the mother was the affected parent. The prevalence of glaucoma was significantly greater in the group with pseudoexfoliation (p <0.0001). Although the presence of age related macular degeneration (ARMD) was highly associated with the presence of pseudoexfoliation, the significance was lost after correction for age (p = 0.69). Although the sample size was small, no association between pseudoexfoliation affected status and cardiovascular disease, cerebrovascular disease, systemic hypertension, or diabetes mellitus was found. CONCLUSIONS: Multiple Icelandic families with pseudoexfoliation in two generations were identified. In all cases where determination was possible, transmission to the second generation was through an affected parent. In each case the affected parent was the mother. Pseudoexfoliation was strongly associated with the presence of glaucoma, but was not associated with either ARMD or systemic disease in this study. These data clearly indicate that pseudoexfoliation is a familial condition and although not conclusive, supports the hypothesis that pseudoexfoliation syndrome is genetically inherited. (+info)
DNA sequence variants in the tyrosinase-related protein 1 (TYRP1) gene are not associated with human pigmentary glaucoma.
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PURPOSE: Pigmentary glaucoma is a common form of glaucoma affecting young adults. Previous studies have suggested that multiple factors, including multiple genetic factors, may be responsible for this condition. Recently, a form of glaucoma associated with pigment dispersion and iris atrophy was identified in the DBA/2J mouse. Abnormalities in the mouse Tyrp1 gene contribute to this condition. The purpose of this study was to determine if DNA sequence variants in the human TYRP1 gene are associated with pigmentary glaucoma in humans. METHODS: The protein coding regions and intron/exon boundaries of the human TYRP1 gene were sequenced using genomic DNA samples from probands from pedigrees affected by pigment dispersion syndrome and pigmentary glaucoma. RESULTS: Three novel synonymous single nucleotide polymorphisms (SNPs) were found in two affected individuals. However, these polymorphisms did not define a haplotype that segregated with the disease in the families. DNA sequence variants that altered the amino acid sequence of TYRP1 were not found. CONCLUSIONS: Despite the phenotypic similarity between the glaucoma in the DBA/2J mouse and human pigmentary glaucoma, the results of this study suggest that DNA sequence variants in the human TYRP1 gene are not associated with inherited pigmentary glaucoma in humans. (+info)
Pseudoexfoliation and sensorineural hearing loss.
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AIMS: There is increasing evidence that pseudoexfoliation (PXF) not only affects ocular anterior segment structures, but may also be a systemic disease. This study was undertaken to assess the relationship between PXF and sensorineural hearing loss. METHODS: Patients with PXF were identified from hospital records and underwent complete ocular examination. The sum of pure-tone hearing thresholds measured at 1, 2 and 3 kHz (HTL1,2,3) in each ear was compared with the ISO 7029 standard sex-matched, median age-associated hearing loss summed over the same frequencies (AAHL1,2,3). The proportion of ears with thresholds higher than the ISO 7029 median AAHL1,2,3 on the same side as eyes without PXF was compared with the proportion of ears ipsilateral to eyes with PXF but without glaucoma and similarly the proportion of ears on the same side as eyes with PXF and glaucoma. RESULTS: In total, 69 patients were studied, of whom 39 were male (56.5%). The mean age of the male patients was 75.8 years, while that of the female group was 75.1 years. All patients had PXF affecting at least one eye. Overall 101 ears (73.7%) had a higher HTL1,2,3 than the ISO 7029 median AAHL1,2,3 which included 56 ears of 78 in the male group (71.8%) and 45 ears of 59 in the female group (76.3%). There was no significant difference between the proportion of ears with HTL1,2,3 higher than the ISO 7029 median AAHL1,2,3 on the same side as eyes without PXF, with PXF but not glaucoma and with PXF and glaucoma, in either the male or female groups. CONCLUSIONS: A large proportion of patients with PXF have sensorineural hearing loss in comparison to age-matched controls, regardless of whether or not there is associated glaucoma. This finding supports the theory that PXF may be a systemic condition. (+info)