Prevalence of mutations in TIGR/Myocilin in patients with adult and juvenile primary open-angle glaucoma.
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Adult↗
Biomedical subjects
R R Allingham
Publications and source records attributed to R R Allingham.
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↗
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↗
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↗
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↗
Rate of progression in open-angle glaucoma estimated from cross-sectional prevalence of visual field damage.
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Cross-Sectional Studies↗
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↗
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↗
Argon vs diode laser trabeculoplasty.
PURPOSE: To compare the efficacy of diode laser and argon laser trabeculoplasty in a randomized prospective study of 11 paired fellow eyes. METHODS: Fellow eyes of 11 patients, having had no prior laser trabeculoplasty and requiring laser trabeculoplasty to lower intraocular pressure, were randomly assigned prospectively to diode laser trabeculoplasty in one eye and argon laser trabeculoplasty in the other eye. RESULTS: In the diode laser group, the average baseline intraocular pressure was 21.6 +/- 2.0 mm Hg before trabeculoplasty and 19.6 +/- 2.1 mm Hg (or a 7.7% +/- 11.5% mean pressure reduction) at 1 month, 19.3 +/- 2.6 mm Hg (or a 6.9% +/- 13.5% mean reduction) at 2 months, and 19.0 +/- 3.3 mm Hg (or a 2.4% +/- 16.9% mean reduction) at 3 months postoperatively. In the argon laser group, the average intraocular pressure was 24.4 +/- 3.5 mm Hg before treatment and 17.6 +/- 1.7 mm Hg (or a 24.7% +/- 11.4% mean pressure reduction) at 1 month, 16.8 +/- 2.5 mm Hg (or a 26.7% +/- 15.3% mean reduction) at 2 months, and 15.5 +/- 1.2 mm Hg (or a 30.0% +/- 16.5% mean reduction) at 3 months after laser trabeculoplasty. The difference between argon and diode laser intraocular pressure reduction was statistically significant at 1 month (P < .01), 2 months (P < .01), and 3 months (P < .05) after treatment. CONCLUSION: Argon laser trabeculoplasty appears to be more effective than diode laser therapy in lowering intraocular pressure during the first 3 months after treatment.
Aged↗
Reduction of IOP after PRK.
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Contraindications↗
Physicians' guide to interactions between glaucoma and systemic medications.
PURPOSE: To develop a Physicians' Guide to assist clinicians in the concomitant use of glaucoma and systemic medications. METHODS: The records of 100 consecutive patients with chronic open-angle glaucoma were retrospectively studied to determine the most common systemic medications that are prescribed in this population. The ten most common drug classes were then used to construct a guide to potential interactions and side effects when these medications are used concomitantly with glaucoma drugs. RESULTS: Eighty-four patients were receiving 1 or more medications (a mean of 3.5) for a mean of 2.6 systemic conditions. Systemic antihypertensive agents was the most common class of drugs, being used by 48 patients. Aspirin, the most common single systemic drug, was being used by 25 patients. CONCLUSIONS: A high percentage of patients with chronic open-angle glaucoma receive a wide variety of medications for coexisting systemic disorders. The concomitant use of glaucoma and systemic medications creates the potential for drug interactions, as well as side effects for both groups of drugs, for which the Physicians' Guide may be beneficial.
Adrenergic beta-Antagonists↗
Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias.
BACKGROUND: Periodic vestibulocerebellar ataxia is an autosomal dominant disorder characterized by defective smooth pursuit, gaze-evoked nystagmus, ataxia, and vertigo. The age of onset ranges from the third to the sixth decade. To date, all patients have originated from North Carolina, suggesting a single common founder. OBJECTIVE: To clarify the classification of periodic vestibulocerebellar ataxia by determining whether it is allelic to other autosomal dominant cerebellar ataxias for which genes have been either localized or identified. METHODS: Blood was collected and DNA isolated from 66 subjects (19 affected individuals) in two multigenerational families. The microsatellite markers used in the analysis either flanked or were tightly linked to the disease gene regions. Two-point and multipoint linkage analyses were performed to define the limits of exclusion. RESULTS: Periodic vestibulocerebellar ataxia was excluded from loci linked to spinocerebellar ataxia type 1 (chromosome 6p), type 2 (chromosome 12q) type 3/Machado/Joseph disease (chromosome 14q), type 4 (chromosome 16q), and type 5 (11cent) as well as to episodic ataxia with myokymia (chromosome 12p), episodic ataxia with nystagmus (chromosome 19p), acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (chromosome 19p), and dentatorubral-pallidoluysian atrophy/Haw River syndrome (chromosome 12p). CONCLUSION: Periodic vestibulocerebellar ataxia is genetically distinct from those autosomal dominant ataxias for which chromosomal localization has been established.
Alleles↗
Schlemm's canal and primary open angle glaucoma: correlation between Schlemm's canal dimensions and outflow facility.
The purpose of the study was to examine the correlation between outflow facility and morphometric measurements of Schlemm's canal (SC) in normal and glaucomatous human eyes. Outflow facility was measured in ten normal and five glaucomatous (POAG) human eyes prior to perfusion-fixation at a pressure of 15 mmHg. Two separate sections per quadrant (eight sections per eye) were analysed using a morphometric analysis system. SC cross sectional area, perimeter, and inner wall length were measured. Inner wall endothelial nuclei were counted. When pooled data were examined, a statistically significant correlation was found between facility and SC area (P < or = 0.01). Most importantly, POAG eyes had a significantly smaller SC cross-sectional area, SC perimeter and SC inner wall length compared to normal eyes. If examined as a reduction in SC filtering area, this decrease in SC inner wall length alone could account for approximately 41-55% of the difference in outflow facility observed between normal and POAG eyes. The dimensions of Schlemm's canal in glaucomatous human eyes were significantly smaller than those in normal eyes. This reduction in SC dimensions may account for approximately half of the decrease in outflow facility observed in POAG eyes.
Aged↗
The distinction between juvenile and adult-onset primary open-angle glaucoma.
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Adult↗
Apraclonidine 0.5% versus 1% for controlling intraocular pressure elevation after argon laser trabeculoplasty.
BACKGROUND AND OBJECTIVE: Topical apraclonidine hydrochloride 1% is effective for controlling the intraocular pressure (IOP) rise following argon laser trabeculoplasty (ALT). The 0.5% formulation has recently become available commercially. The objective of this study was to compare the efficacy of these two concentrations for controlling IOP after ALT. PATIENTS AND METHODS: All patients undergoing ALT were prospectively randomized to receive either 1% or 0.5% apraclonidine 1 hour before and immediately after the laser surgery. IOP was measured before and 2 and 24 hours after the treatment. RESULTS: No statistically significant difference in mean IOPs was found between the two treatment groups at any time. CONCLUSION: These data suggest that 0.5% and 1% apraclonidine are equally effective for preventing IOP rise after ALT.
Administration, Topical↗
Comparative study of the efficacy of argon laser trabeculoplasty for exfoliation and primary open-angle glaucoma.
PURPOSE: To investigate the efficacy of argon laser trabeculoplasty (ALT) for the treatment of primary open-angle glaucoma (POAG) and of glaucoma associated with exfoliation syndrome (EXF). METHODS: Review of > 200 charts from patients treated with ALT between 1981 and 1987 identified 66 POAG and 29 EXF eyes that underwent initial 180 degrees treatment. Variables including baseline intraocular pressure (IOP), age, sex, angle pigmentation, and follow-up IOP were studied with numerous statistical analyses. Multiple failure modes were used to define failure rate. All POAG and EXF patients were white. RESULTS: The baseline pre-ALT IOP was 23.2 +/- 6.1 mm Hg for the POAG group and 25.8 +/- 5.9 mm Hg for the EXF group (p < .06). Mean follow-up time was 27 +/- 22 months for POAG eyes and 23 +/- 20 months for EXF eyes. Using failure mode 4 (glaucoma surgery, third laser, IOP < or = 22 mm Hg, or two consecutive IOPs > 85% of original baseline IOP), the 1-year failure rates were 40% (POAG) and 18% (EXF), and the 3-year rates were 58% (POAG) and 47% (EXF), p < 0.89 by log-rank test. A Cox proportional hazards model controlling for baseline IOP, age, sex, and angle pigmentation demonstrated that exfoliation status did not affect progression to filtering surgery (p > 0.60). CONCLUSION: Using multiple failure modes, the results suggest that the success rate of ALT in exfoliation glaucoma tends to decrease over time, but then stabilizes at this reduced value at a level similar to that of POAG. By 3 years, there is a substantial failure rate in both POAG eyes and EXF eyes. Although the initial response to ALT in EXF patients is greater, the long-term outcome is similar for both groups.
Exfoliation Syndrome↗
Factors associated with visual acuity loss after noncontact transscleral Nd:YAG cyclophotocoagulation.
PURPOSE: To determine the factors associated with visual acuity loss following transscleral Nd:YAG cyclophotocoagulation (TYC). METHODS: The authors retrospectively studied 479 patients followed for a mean of 22 months after the initial TYC in one eye and analyzed the data with univariate and multivariate analysis for the factors associated with visual acuity loss. Data analyzed included age, race, sex, preoperative intraocular pressure (IOP) and visual acuity, type of glaucoma, total energy per treatment, number of retreatments, final IOP, and duration of follow-up. RESULTS: The preoperative factors associated with visual acuity loss after TYC as determined by both univariate and multivariate analysis were neovascular glaucoma (p = 0.001, odds ratio = 2.80) and black race (p = 0.044, odds ratio = 1.67). Postoperative hypotony and follow-up of > 6 months were also associated with visual acuity loss (p < 0.001, odds ratio = 6.68 and p = 0.046, odds ratio = 2.61, respectively). CONCLUSIONS: Transscleral Nd:YAG cyclophotocoagulation is associated with a greater risk of visual acuity loss in patients with neovascular glaucoma and in the black population. Postoperative hypotony is associated with a poor visual outcome, whereas the association with longer follow-up duration suggests that other factors, related to the patient's underlying disease, are also significant factors.
Adolescent↗
Retroperfusion studies of the aqueous outflow system. Part 2: Studies in human eyes.
PURPOSE: To extend the retroperfusion technique to allow the delivery of drugs into Schlemm's canal in enucleated human eyes and to use this technique to gain insights into the function of the inner wall of Schlemm's canal. METHODS: Using our previously developed retroperfusion technique, the anterior chamber of enucleated human eyes was held at a small negative pressure (-0.75 mm Hg), and fluid was allowed to flow retrograde from the limbal vessels, through the collector channels, and into Schlemm's canal. In this manner, the sulfhydryl agent N-ethyl maleimide (NEM) or the fixative agent glutaraldehyde was delivered to the inner wall of Schlemm's canal in normal and glaucomatous human eyes. Facility changes caused by retroperfusion were measured and correlated with histologic studies of the inner wall of Schlemm's canal. RESULTS: Retroperfusion effectively delivers fluid from the scleral surface into the lumen of Schlemm's canal. Retroperfusion with vehicle alone does not alter facility or change outflow pathway morphology. Retroperfusion with NEM causes an approximately 35% facility increase and concomitant inner wall openings. Retroperfusion with glutaraldehyde in normal eyes and eyes with primary open-angle glaucoma causes a facility decrease of 53% and 64%, respectively, and localized fixation of the inner wall of Schlemm's canal. The magnitude of the facility changes caused by retroperfusion were similar to those seen using conventional forward perfusion of NEM and glutaraldehyde. CONCLUSIONS: Retroperfusion is a viable technique for the delivery of drugs or other agents into Schlemm's canal in enucleated human eyes. Retroperfusion-induced changes in outflow facility are correlated strongly with morphologically observed alterations in inner wall structure. The majority of outflow resistance is localized to the inner wall of Schlemm's canal or the immediately adjacent 10-microns region of the juxtacanalicular tissue in normal eyes and in eyes with primary open-angle glaucoma. Inner wall giant vacuoles and pores likely persist for sometime, even after fixation at zero or negative pressure.
Anterior Eye Segment↗