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Biomedical subjects

R R Allingham

Publications and source records attributed to R R Allingham.

At least 19 recordsLinked to original sources
PubMed2000

Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor.

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.

Amino Acid Sequence↗
PubMed2000

Genome-wide scan for adult onset primary open angle glaucoma.

Adult onset primary open angle glaucoma is a leading cause of blindness throughout the world. The disease results in an apoptotic death of retinal ganglion cells that is usually associated with an elevation of intraocular pressure. Familial aggregation of the disorder provides evidence for strong genetic influences that are likely to be the result of multiple susceptibility genes. A two-stage genome scan to identify the genomic locations of glaucoma susceptibility genes was performed using an initial pedigree set of 113 affected sibpairs and a second pedigree set of 69 affected sibpairs. Linkage analysis was performed using both model-dependent (lod score) and model-independent affected relative pair and sibpair methods. Twenty-five regions identified by the initial scan were further investigated using the second pedigree set. In the combined data analysis, regions located on chromosomes 2, 6, 9, 11, 14, 17 and 19 continued to produce model-dependent lod scores and/or an MLS >1.0, while five regions (2, 14, 17p, 17q and 19) produced an MLS >2. 0. Multipoint analysis using ASPEX also showed significant results on chromosomes 2, 14, 17p, 17q and 19. These results are an important step towards the identification of genes responsible for the genetic susceptibility to this blinding condition.

Age of Onset↗
PubMed2000

Excisional bleb revision to correct overfiltration or leakage.

OBJECTIVES: To evaluate the effectiveness of excisional revision of filtering blebs for hypotony or leakage when more conservative measures have failed. PATIENTS AND METHODS: Retrospective review of all patients who underwent excisional revision of a filtering bleb for hypotony (intraocular pressure [IOP] < 5 mm Hg) or leakage during a 3 year period. The revision consisted of excision of the avascular bleb, mobilization of the surrounding conjunctiva, and suturing of the conjunctiva at the limbus. RESULTS: Sixteen patients were included in the study. The average age was 66.3 +/- 14.8 years (range, 39-83). Revision followed trabeculectomy in 11 cases, combined phacoemulsification-trabeculectomy in three cases, and inadvertent blebs in two cases. Five cases had bleb leaks without hypotony, four cases had hypotony alone, and seven cases had both hypotony and a bleb leak. Average follow-up after bleb revision was 25 +/- 11 months (range, 9-43). Average IOP increased from 3.8 +/- 5.6 mm Hg (range, 0-22) to 11.9 +/- 4.1 mm Hg (range, 3-18), with an average of 1.1 +/- 1.1 medication (range, 0-3). The IOP at the last visit was < 15 mm Hg in all but two patients, with 10 of the 16 patients requiring medications. At the last follow-up examination, visual acuity had improved > or = two lines in nine patients and was reduced two lines in one patient. Five patients had early postoperative limbal wound leaks; resuturing was required in one case. CONCLUSIONS: Excisional bleb revision is an effective technique to correct hypotony or leakage after filtering surgery when other methods have failed. Intraocular pressure control is often maintained with the use of medications.

Adult↗
PubMed2000

Isolation of primary open-angle glaucomatous trabecular meshwork cells from whole eye tissue.

PURPOSE: Isolation and culture of human trabecular meshwork (TM) cells from primary open-angle glaucomatous (POAG) tissue has proven difficult. The objective of this study was to directly compare the utility of two different isolation methods to obtain viable human TM cells from POAG whole eye tissue. METHODS: Using a blunt dissection technique, human TM tissue was obtained from four pairs of donor eyes (67, 77, 81 and 82 years) with a documented history of POAG. TM tissue from one eye was explanted into tissue culture. TM from the contralateral eye was digested with a collagenase mixture and seeded onto culture plates. RESULTS: Primary cell isolates were obtained from all donors with both techniques. However, only cells obtained using the digestion method (3 of 4 TMs) could be passaged for expansion and freeze-downs (3 x 107 second passage cells/donor). None of the cells obtained from explanted TMs could be passaged. Cells from successful isolations were of uniform size, possessed typical TM morphology and had doubling times < 48 hours. CONCLUSION: These results demonstrate a clear advantage to digesting the extracellular matrix of glaucomatous TM tissue to obtain sufficient numbers of healthy cells for use in experiments. In contrast to cells obtained from explants, cells liberated from POAG TM tissue by digestion appear indistinguishable morphologically and behaviorally from "normal" TM cells.

Aged↗
PubMed1999

Excimer laser effects on outflow facility and outflow pathway morphology.

PURPOSE: To determine the relative contributions to aqueous outflow resistance of the tissues distal to the inner wall of Schlemm's canal. METHODS: While performing constant pressure perfusion at 10 mm Hg, a 193-nm excimer laser (Questek) was used to precisely remove portions of sclera, unroofing Schlemm's canal while leaving the inner wall intact. The laser beam was masked to produce a beam 2 mm by 1 mm. The laser output was constant at a fluency of 75 mJ/cm2 and 20 Hz. The excimer laser at a frequency of 1 Hz was used as the aiming beam. Photoablation was performed on human cadaver eyes at the limbus at an angle of 0 degrees to 45 degrees from the optical axis. As the excimer photoablations progressed, Schlemm's canal was visualized by the fluorescence of the Barany's solution containing fluorescein dye. After perfusion fixation the eyes were immersion-fixed overnight. The facility of outflow before (Co) and after (Ce) the excimer ablation was measured in 7 eyes. RESULTS: The facility of outflow increased in all eyes after the excimer sinusotomy, from a mean of 0.29+/-0.02 before the sinusotomy to 0.37+/-0.03 microl/min per mm Hg after (P < 0.05). The mean ratio of outflow facility after and before ablation (Ce/Co) was 1.27+/-0.08 (range, 1.20-1.39), a reduction of outflow resistance of 21.3%. Using the formula of Ellingsen and Grant (1972), percentage of resistance to outflow eliminated = 100 [1 - alphaCo/Ce - (1 - alpha)Co], where alpha = fraction of the circumference dissected. Assuming that because of circumferential flow approximately 50% of Schlemm's canal is drained by the single opening made in the outer wall ablation studies, this results in resistance to outflow eliminated of 35%, which is consistent with the calculated eliminated resistance derived from the data of Rosenquist et al., 1989. Light and scanning electron microscopy confirmed the integrity of the inner wall Schlemm's canal underlying the area of ablation. CONCLUSIONS: The results provide direct evidence indicating that approximately one third of resistance to outflow in the human eye lies distal to the inner wall Schlemm's canal in an enucleated perfused human eye.

Anterior Chamber↗
PubMed1998

Laser energy reaching the posterior pole during transscleral cyclophotocoagulation.

OBJECTIVE: To measure scattered laser energy reaching the posterior pole during transscleral cyclophotocoagulation. METHODS: Transscleral cyclophotocoagulation was performed on 4 cadaver eyes with Nd:YAG noncontact, Nd:YAG contact, and diode contact lasers. Energy was measured with a photodiode through a 7-mm trephined hole in the posterior pole. Average percentage power, average power, and average energy transmission were calculated. American Conference of Governmental Industrial Hygienists (ACGIH) guidelines were used to calculate allowable energy exposures for each laser. RESULTS: All 3 lasers transmitted 3% to 5% of the power to the posterior pole. The average energy transmission was 240 to 260 mJ for all lasers. The contact lasers had an average power transmission of 120 mW. The noncontact Nd:YAG laser, with shorter pulse duration, had an average power transmission of 13,000 mW, significantly greater than that of the other lasers. The ACGIH guidelines for allowable energy exposures were 93 mJ for the noncontact Nd:YAG laser, 1300 mJ for the contact Nd:YAG laser, and 440 mJ for the contact diode laser. CONCLUSIONS: Three percent to 5% of laser power delivered during cyclophotocoagulation reaches the posterior pole. Exposure energies may approach or exceed ACGIH guidelines. The clinical significance of these findings remains to be shown.

Aged↗
PubMed1998

Quantitative DNA pooling to increase the efficiency of linkage analysis in autosomal dominant disease.

DNA pooling is an efficient method to rapidly perform genome-wide linkage scans in autosomal recessive diseases in inbred populations where affected individuals are likely to be homozygous for alleles near the disease gene locus. We wanted to examine whether this approach would detect linkage in autosomal dominant (AD) disorders where affected individuals may share one allele identical by descent at loci tightly linked to the disease. Two large outbred pedigrees in which the AD diseases familial venous malformation (FVM) and hereditary hemorrhagic telangiectasia (HHT1), linked to 9p and 9q, respectively, were investigated. Separate pools of DNA from affected (n = 21 for FVM and 17 for HHT1) and unaffected family members (n = 9 FVM and HHT1), and 25 unrelated population controls were established. Polymorphic markers spanning chromosome 9 at approximately 13.5-cM intervals were amplified using standard PCR. Allele quantitation was performed with a fluorimager. Visual inspection of allele intensities and frequency distributions suggested a shift in frequency of the most common allele in the affecteds lane when compared to control lanes for markers within 30 cM of the FVM and HHT1 loci. These subjective assessments were confirmed statistically by testing for the difference between two proportions (one-sided; P < or = 0.05). When using population controls, the true-positive rates for FVM and HHT1 were 5/5 and 2/5 markers, respectively. False-positive rates for FVM and HHT1 were 3/9 and 2/9, respectively. In both AD diseases investigated, quantitative DNA pooling detected shifts in allele frequency, thus identifying areas of known linkage in most cases. The utility of this technique depends on the size of the pedigree, frequency of the disease-associated allele in the population, and the choice of appropriate controls. Although the false-positive rate appears to be high, this approach still serves to reduce the amount of overall genotyping by about 60%. DNA pooling merits further investigation as a potential strategy in increasing the efficiency of genomic linkage scans.

Alleles↗
PubMed1998

Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber syndrome.

PURPOSE: To determine if latanoprost reduces intraocular pressure in eyes with glaucoma associated with Sturge-Weber syndrome. METHODS: We conducted a prospective study in which eyes with uncontrolled intraocular pressure associated with Sturge-Weber syndrome were treated with latanoprost 0.005% once daily. All eyes were already receiving at least two other antiglaucoma medications. Intraocular pressure was measured at baseline and after treatment for at least 1 month. All intraocular pressure measurements were taken within 24 hours of drug instillation. RESULTS: Six eyes of six patients received latanoprost. Two (28%) of the six eyes demonstrated an intraocular pressure decrease that averaged 8.8 mm Hg. These two responders had juvenile onset glaucoma, whereas the four nonresponders had congenital onset glaucoma. CONCLUSIONS: Latanoprost may significantly reduce intraocular pressure in selected patients with glaucoma associated with Sturge-Weber syndrome.

Adolescent↗
PubMed1998

A clinical comparison of transscleral cyclophotocoagulation with neodymium: YAG and semiconductor diode lasers.

PURPOSE: To compare the efficacy of transscleral cyclophotocoagulation using a neodymium: YAG (Nd:YAG) or semiconductor diode laser in controlling intraocular pressure in patients with refractory glaucoma. METHODS: In a prospective study, 95 eyes of 91 patients with refractory glaucoma randomly received Nd:YAG or diode cyclophotocoagulation. Patients were followed for a mean of 10.4 months (10.42 +/- 3.16, mean +/- SD). We compared available data preoperatively and at 1 week, 1 month, 6 months, and 12 months postoperatively. Data analyzed were corrected visual acuity, intraocular pressure, and the type of glaucoma. RESULTS: There was a statistically significant decrease in intraocular pressure after both Nd:YAG and diode cyclophotocoagulation at each time period. However, there were no significant differences in postoperative intraocular pressure or visual acuity change between Nd:YAG and diode procedures. CONCLUSIONS: Compared with the Nd:YAG laser for transscleral cyclophotocoagulation, the diode laser has technological advantages including portability, durability, and smaller size, while providing equivalent postoperative intraocular pressure and visual acuity change.

Adult↗
PubMed1998

Is pseudoexfoliation syndrome inherited? A review of genetic and nongenetic factors and a new observation.

Pseudoexfoliation (PEX) syndrome is the commonest identifiable cause of open-angle glaucoma worldwide. PEX is characterized clinically by small whitish deposits of fibrillar-granular material in the anterior segment of the eye. Despite its prevalence and potential for ophthalmic morbidity, surprisingly little is known about the etiology and pathogenesis of PEX. This article reviews the literature and presents evidence regarding genetic and nongenetic arguments for the etiology of pseudoexfoliation. Lines of evidence that support a genetic basis for PEX include transmission in two-generation families, twin studies, an increased risk of PEX in relatives of affected patients, and HLA studies. Nearly all pedigrees in the literature, and our own experience with PEX families in Iceland and Canada, suggest maternal transmission, raising the possibilities of mitochondrial inheritance, X-linked inheritance, and autosomal inheritance with genomic imprinting. A number of nongenetic factors have also been evaluated for their possible implication in the development of PEX. These include ultraviolet light, autoimmunity, slow virus infection, and trauma. It is possible that a combination of genetic and nongenetic factors may be involved in the etiology and pathogenesis of PEX, i.e. it may be a multifactorial disorder. Further studies with larger numbers of patients are needed to delineate more clearly the contribution of genetic (nuclear DNA, mitochondrial DNA or both) and nongenetic factors to the development of pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

Autoimmunity↗
PubMed1998

Results of trabeculectomy with 0.3 mg/ml mitomycin C titrating exposure times based on risk factors for failure.

PURPOSE: To examine the efficacy of trabeculectomy with mitomycin C 0.3 mg/ml using titrated exposure times. METHODS: A retrospective chart review of consecutive patients undergoing trabeculectomy in an academic referral glaucoma clinic was performed. All patients received trabeculectomies performed by one surgeon (M.B.S.). The study included 57 eyes of 57 patients using mitomycin C with exposure times titrated from one to five minutes based on risk factors for trabeculectomy failure. Surgical success was defined as a final intraocular pressure (IOP) of less than 21 mmHg with or without medications or a 25% reduction in IOP if preoperative IOP was 21 mmHg or less. Patients requiring repeat trabeculectomies were considered failures regardless of their final IOP. Patients receiving different mitomycin C exposure times were compared but statistical analysis was not used because these subgroups were not randomized. RESULTS: An overall surgical success rate of 84.2% was achieved at a mean follow-up of 11.9 months. The surgical success rate and percentage IOP reduction was similar between exposure time subgroups. Hypotonous maculopathy observed in three patients (5.3%). All cases of hypotonous maculopathy was occurred in the lower-risk patients receiving one to three minute exposure times to mitomycin C. CONCLUSIONS: We believe mitomycin C should be used sparingly if at all in patients at lower risk for trabeculectomy failure. This concentration of mitomycin C with four to five minute exposure times appears to be efficacious for patients with multiple risk factors for trabeculectomy failure.

Administration, Topical↗
PubMed1998

Gln368STOP myocilin mutation in families with late-onset primary open-angle glaucoma.

PURPOSE: To examine families ascertained for late-onset primary open-angle glaucoma (POAG) to determine mutations in the gene coding for myocilin. METHODS: The diagnosis of late-onset POAG was defined as age at diagnosis more than 35 years, intraocular pressure (IOP) 22 mm Hg or more in both eyes or 19 mm Hg or more while the patient was taking two glaucoma medications, glaucomatous optic neuropathy in both eyes, and visual field loss consistent with optic nerve damage in at least one eye of the proband. Two of three criteria were required in other family members. DNA from all families was screened for polymorphisms in myocilin using single-strand conformation polymorphism analysis. All polymorphisms were sequenced for mutations. RESULTS: Eighty-three affected people in 29 families with late-onset POAG were screened for mutations. Three mutations, two novel missense (Thr377Met and Glu352Lys) and one nonsense (Gln368STOP), were identified. The missense mutations did not segregate with the disease phenotype in these families. The nonsense mutation was found in 3 of 29 unrelated families with POAG. All affected family members and 8 of 12 in whom glaucoma was suspected had the Gln368STOP mutation. All people with this mutation had elevated IOP, and 78% had POAG by age 70. CONCLUSIONS: Three mutations were identified in the gene coding for myocilin in families with late-onset POAG. Of these, the Gln368STOP mutation was highly associated with the development of glaucoma. All people with this mutation had glaucoma or elevated IOP by age 70. In the United States, the Gln368STOP mutation in myocilin is strongly associated with the development of late-onset POAG. However, factors in addition to the presence of this mutation seem to play a role in the development of ocular hypertension and glaucoma in these families.

Adult↗
PubMed1998

Decrease in intraocular pressure after orbital decompression for thyroid orbitopathy.

BACKGROUND: The effect of thyroid orbitopathy on intraocular pressure (IOP) remains controversial. We carried out a study to determine the effect of orbital decompression surgery on the IOP in patients with advanced thyroid orbitopathy. METHODS: The records of 12 consecutive patients (22 eyes) who underwent decompression surgery for severe thyroid orbitopathy between 1985 and 1996 were reviewed. All patients were maintained on essentially the same medications before and after surgery. The IOP readings, obtained by means of applanation tonometry in primary gaze, from the pre- and postoperative visits were recorded, and the net change was calculated. RESULTS: The mean preoperative and postoperative IOP values were 19.8 mm Hg and 16.8 mm Hg respectively, a significant difference (p = 0.008). Seven of eight eyes with an IOP of 21 mm Hg or greater preoperatively had a postoperative IOP less than 21 mm Hg; these eyes showed a mean decrease in IOP of 5.6 mm Hg. The degree of preoperative IOP elevation was found to be a strong predictor of the amount of IOP lowering after surgery (p = 0.014). INTERPRETATION: Our results support the concept that orbital congestion associated with thyroid orbitopathy produces an increase in IOP by elevation of episcleral venous pressure (EVP) and that orbital decompression may reduce the IOP by decreasing EVP. Decompression surgery may obviate the need for more aggressive management of glaucoma in patients with severe thyroid orbitopathy.

Adult↗
PubMed1997

Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes.

OBJECTIVE: To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes. METHODS: One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects. RESULTS: The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02). CONCLUSIONS: The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.

Aged↗
PubMed1997

Efficacy of autologous blood injection for treating overfiltering or leaking blebs after glaucoma surgery.

PURPOSE: To evaluate the efficacy of autologous blood injections for treating overfiltering or leaking blebs after glaucoma surgery. METHOD: Retrospective review of ten eyes of ten patients who received intrableb autologous blood injections for hypotonous maculopathy. RESULTS: After intrableb blood injection, average intraocular pressure increased from 4.3 mm Hg to 6.4 mm Hg, and average visual acuity improved from 20/88 to 20/77. These results, however, were not statistically significant. CONCLUSION: Our results with autologous blood injection are less favorable than those of previous reports, although further study with a larger case series is needed.

Adult↗
PubMed1997

Molecular genetics is revolutionizing our understanding of ophthalmic disease.

PURPOSE: To inform ophthalmologists of the extraordinary progress in molecular genetics that is revolutionizing our understanding of ophthalmic disease and of the crucial role of the clinician in facilitating genetic discovery. METHOD: Review of relevant articles. RESULTS: Genes for many mendelian-inherited eye diseases have been localized and some identified using three general approaches: positional cloning, which requires no knowledge of underlying pathophysiology; a candidate gene approach, which examines genes based on their likely function; and a positional candidate approach, which uses map location as well as candidate genes in the linked region to isolate a gene. In positional cloning, once linkage is obtained, the gene can eventually be isolated, cloned, and sequenced and mutations identified. Techniques in molecular biology and other disciplines can then be used to unravel the pathophysiology of a disease. CONCLUSIONS: Molecular genetics is advancing our understanding of the classification and pathophysiology of ophthalmic diseases. The present classification system, based largely on clinical description of disease, is being replaced with a more rational classification based on genetic causes. Future research will determine the function of known genes and identify susceptibility loci for complex diseases such as chronic open-angle glaucoma and age-related macular degeneration. More specific diagnostic, therapeutic, and preventive strategies for ophthalmic disease will be developed. Clinicians play a crucial role by inquiring about the family history of all patients, identifying individuals and families with a genetic trait, and, when appropriate, referring them for further investigation.

Chromosome Mapping↗