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K F Damji

Publications and source records attributed to K F Damji.

At least 19 recordsLinked to original sources
PubMed2001

Familial occurrence of pigment dispersion syndrome.

BACKGROUND: Pigment dispersion syndrome affects up to 4% of the white population. It is characterized by the presence of transillumination defects, Krukenberg's spindle and dense trabecular meshwork pigmentation. Open-angle glaucoma will develop in as many as 50% of affected patients. In this study we describe the familial occurrence of pigment dispersion syndrome in six North American pedigrees and the phenotypic characteristics with respect to pigment dispersion syndrome and glaucoma. METHODS: Probands with pigment dispersion syndrome were identified in glaucoma clinics at university eye centres in Ottawa and Durham, NC. Families with two or more affected members were evaluated. All willing members in each family underwent a thorough clinical examination and were classified as affected with pigment dispersion syndrome, suspect or unaffected. The previous medical records were reviewed to obtain the past medical and ocular history, including risk factors for glaucoma. RESULTS: All six families are white. Three families show at least two generations of affected members. Of the 43 subjects examined 58% were women. All 14 affected members showed moderate to heavy trabecular meshwork pigmentation and either Krukenberg's spindle or transillumination defects. The affected members were also considerably more myopic (mean spherical equivalent for the right eye -4.72 dioptres) than the suspect group or the unaffected group (mean spherical equivalent -0.79 D and +1.19 D respectively) (p < or = 0.001), and the intraocular pressure was higher for the affected than the unaffected group (mean for the right eye 20 mm Hg vs. 16 mm Hg) (p = 0.004). Half of those affected also had open-angle glaucoma. INTERPRETATION: We have identified and phenotypically characterized six North American families with autosomal dominant pigment dispersion syndrome. Our ultimate goal is to identify the gene(s) that causes this disorder in order to clarify its molecular etiology and pathophysiology. This may give rise to a molecular classification of the disease as well as provide the foundation for genetic testing and new treatment approaches.

Adult↗
PubMed2000

Familial occurrence of artefactual ocular hypertension from thick corneas and of primary open angle glaucoma in a French Canadian kindred.

We describe the coexistence of artefactual ocular hypertension due to increased central corneal thickness (CCT>585 microm), with primary open angle glaucoma (POAG) in a French Canadian kindred. Seventeen members of the family were examined and classified as to their glaucoma status. The mean CCT for our glaucoma patients (580 microm; n=5) and that for normals (552 microm; n=6) were within two standard deviations of the mean value provided in the literature (531 microm +/- SD=29 microm). The mean CCT of 611 microm for the suspect group (n=6) was considerably higher than for the glaucoma and normal groups. All but one of the suspects were classified as ocular hypertensives on the basis of high intraocular pressures (IOPs). When the IOPs for these patients (mean 22.6 mmHg) were corrected for their CCTs, all had pressures of <21 mmHg (mean 16.4 mmHg). Ten of the seventeen family members had thick CCTs, and transmission of thick corneas was seen in two generations. A number of individuals in this family had optic nerve head drusen (9/17) and the mean CCT of these individuals (601 microm) was higher than the mean CCT (560 microm) of the group without drusen (P=0.020 by t test). Artefactual ocular hypertension and POAG can be present in different members of the same family. The presence of a thick cornea appears to be an inherited trait and may be associated with the presence of optic nerve drusen. This association suggests a developmental relationship between thick corneas and optic nerve head drusen which needs to be studied further.

Aged↗
PubMed1999

Childhood-onset primary open angle glaucoma in a Canadian kindred: clinical and molecular genetic features.

OBJECTIVE: To describe the clinical features and identify the molecular etiology of childhood-onset primary open angle glaucoma (POAG) in a Canadian kindred. METHODS: Members of a Canadian Caucasian family with POAG were examined and DNA obtained. Single-strand conformation polymorphism analysis was performed using reported primers from exon 3 of the myocilin gene. A single-stranded conformation polymorphism was characterized by polymerase chain reaction-based sequencing. RESULTS: Two affected half-sibs had onset of severe glaucoma at age 3 and 9. Their mother had lost vision in one eye from glaucoma by age 17. All three affected subjects had undergone bilateral glaucoma filtering surgery. Both fathers were unaffected. A single-stranded conformation polymorphism was identified in the mother and the two affected daughters and was absent in one father. A single base change from C-->T at nucleotide position 1109 was identified in the affected members of the family by direct sequencing. This mutation, which causes a nonconservative amino acid change (Pro370Leu), was not found on 192 normal chromosomes from Caucasian individuals. CONCLUSION: We report a Canadian family with childhood-onset, severe POAG due to a mutation in the myocilin gene.

Adult↗
PubMed1999

Selective laser trabeculoplasty v argon laser trabeculoplasty: a prospective randomised clinical trial.

AIMS: To compare the effectiveness of selective laser trabeculoplasty (SLT, a 532 nm Nd:YAG laser) with argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with medically uncontrolled open angle glaucoma. METHODS: A prospective randomised clinical trial was designed. Patients were randomised to treatment with either SLT or ALT and were evaluated at 1 hour, 1 week, 1, 3, and 6 months post-laser. RESULTS: There were 18 eyes in each group. Baseline characteristics were similar in both groups. In the SLT group the mean IOP at baseline, 1, 3, and 6 months was 22.8 (SD 3.0), 20.1 (4.6), 19.3 (6.0), and 17.8 (4.8) mm Hg, respectively. In the ALT group, the mean IOP at baseline, 1, 3, and 6 months was 22.5 (3.6), 19.5 (4.7), 19.6 (5.6), and 17.7 (3.3) mm Hg, respectively. There was a greater anterior chamber reaction, 1 hour after SLT v ALT (p< 0.01). Patients with previous failed ALT had a better reduction in IOP with SLT than with repeat ALT (6.8 (2. 4) v 3.6 (1.8) mm Hg; p = 0.01). CONCLUSION: SLT appears to be equivalent to ALT in lowering IOP during the first 6 months after treatment. There is a slightly greater anterior chamber reaction 1 hour after SLT. Patients with previous failed ALT had a significantly greater drop in IOP when treated with SLT v ALT. These results need to be confirmed with a larger sample size.

Adult↗
PubMed1999

Advances in molecular genetics of glaucoma: a perspective for the clinician.

Extraordinary progress has been made over the last 5 years in improving our understanding of the molecular causes of various glaucomas. Identification of the myocilin gene and of 5 additional genetic loci that play a role in development of primary open angle glaucoma provides us with an opportunity to reclassify this complex phenotype based on underlying cause of disease. Clinicians who obtain a detailed family history from their patients and who have referred families with glaucoma to laboratory investigators are at the forefront of this revolution in molecular genetics. As a result, all clinicians will soon be poised to profit from genetic discoveries by being able to order diagnostic tests that will identify specific genetic mutations. These mutations will provide a detailed understanding of the natural history of the patient's glaucoma, as well as information for genetic counseling. Individuals at risk in the family will be able to be identified, permitting closer follow-up and earlier institution of glaucoma therapy. A new understanding of pathophysiology is developing and will provide the basis for more rational pharmacological and gene therapy approaches in the future. The hope of primary prevention for various glaucomas, once a distant dream, may become reality within our lifetimes.

Chromosomes, Human, Pair 1↗
PubMed1999

Familial occurrence of pseudoexfoliation in Canada.

BACKGROUND: Genetic factors may play an important role in pseudoexfoliation syndrome. We describe the familial occurrence of pseudoexfoliation in Canadian families. METHODS: Probands with pseudoexfoliation were referred to a tertiary care glaucoma service in Ottawa because of a family history of pseudoexfoliation or glaucoma, or both. Probands and family members who agreed to participate underwent a systematic interview and eye examination. The pseudoexfoliation status was classified as affected, suspect or unknown based on preestablished criteria for the diagnosis of pseudoexfoliation and glaucoma. RESULTS: Thirty-four members of 10 families were assessed (18 affected, 2 suspect and 14 status unknown). Six families had two or more generations with pseudoexfoliation, and four families had one generation affected. There was a predominance of females among the affected subjects (17:1), and transmission in all cases appeared to be maternal. Eight of the families were of Irish/Scottish ancestry. Nine (50%) of the affected subjects had cardiovascular disease. Affected subjects tended to be older than suspects and those whose status was unknown (mean age 77, 67 and 55 years respectively). Seven subjects were affected unilaterally and 11 bilaterally. Affected subjects had moderate angle pigmentation in both eyes (mean +2.7, where 0 = no pigment and +4 = dense homogeneous pigment). The mean intraocular pressure in both eyes was higher for the affected subjects (23.1 [standard deviation (SD) 8.6] mm Hg) than for the suspects (16.8 [SD 6.1] mm Hg) and those of unknown status (16.8 [SD 2.9] mm Hg). An enlarged cup:disc ratio was seen in the affected subjects (mean 0.62). Eleven (61%) of the affected subjects had open angles on gonioscopy, and five had occludable angles and required peripheral iridectomy. Ten (56%) of the affected subjects were classified as having glaucoma, and 14 (78%) had evidence of cataract formation in at least one eye. INTERPRETATION: Pseudoexfoliation appears to be transmitted matrilineally, which raises the possibility of mitochondrial inheritance, X-linked inheritance or autosomal inheritance with genomic imprinting. A larger study of families with pseudoexfoliation is necessary to clarify the mode of transmission and to identify the gene(s) involved in the etiology of this disorder.

Adult↗
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

Lattice corneal dystrophy type 1 in a Canadian kindred is associated with the Arg124 --> Cys mutation in the kerato-epithelin gene. sgupta@ogh.on.ca.

PURPOSE: To identify the mutation responsible for lattice corneal dystrophy type 1 in an extended Canadian kindred. METHODS: A search for a mutation in the candidate gene, kerato-epithelin, was carried out by single-strand conformation polymorphism and sequencing analyses. RESULTS: AC --> T mutation at position 417 was detected in exon 4 of the kerato-epithelin gene, which is expected to cause an Arg124 --> Cys change. This is the same nucleotide change described previously in two Swiss families with lattice corneal dystrophy type 1. CONCLUSION: Although the possibility that the three families (two previously described Swiss families and this Canadian kindred) are related has not been excluded, it appears that the unique phenotype of lattice corneal dystrophy type 1 is caused by this particular amino acid change.

Arginine↗
PubMed1998

Positive correlation between Tono-Pen intraocular pressure and central corneal thickness.

OBJECTIVE: To examine the relationship between intraocular pressure (IOP) readings taken by the Tono-Pen tonometer (Mentor O&O, Norwell, MA) and central corneal thickness (CCT). DESIGN: Prospective cross-sectional population study. PARTICIPANTS: There were 651 eyes of 332 healthy subjects. MAIN OUTCOME MEASURES: A questionnaire was given to each subject requesting information on gender, age, race, and other factors that can influence IOP. The IOP then was measured using the Tono-Pen followed by measurements of CCT using an ultrasonic pachymeter. RESULTS: The IOP was found to increase by 2.9 mmHg/100 microns CCT in males and 1.2 mmHg/100 microns in females. For males, CCT was found to be statistically significant in predicting IOP (P < 0.001 in the right and left eyes) and diabetes was of borderline significance (P = 0.012 in the right eye, P = 0.089 in the left eye). For females, CCT was of borderline significance (P = 0.064 in the right eye, P = 0.019 in the left eye). In females, a family history of glaucoma (P = 0.021 in the right eye, P = 0.022 in the left eye) and hypertension (P = 0.010 in the right eye, P = < 0.001 in the left eye) were also significant in the prediction of IOP. Race was found to be a significant predictor of CCT (P < 0.001 in both right and left eyes) for both males and females. CONCLUSION: Clinicians should be aware that, as with the Goldmann applanation tonometer, the Tono-Pen has a systematic error in IOP readings caused by its dependence on CCT. Tono-Pen IOP readings are positively correlated to CCT in males and, to a lesser extent, in females as well. The CCT measurements should be considered to ensure proper interpretation of IOP measurements in the diagnosis and management of disorders in which the CCT or IOP readings are outside normal limits.

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

Correction of intraocular pressure for changes in central corneal thickness following photorefractive keratectomy.

OBJECTIVE: To investigate the relation between measurements of intraocular pressure (IOP) and central corneal thickness (CCT) in myopic patients undergoing photorefractive keratectomy (PRK). DESIGN: Descriptive study. SETTING: University-affiliated eye care centre in Ottawa. PATIENTS: A total of 481 consecutive eyes of 318 patients with a mean preoperative refractive error of -6.50 dioptres treated with excimer PRK between March 1993 and December 1996. OUTCOME MEASURES: IOP measured by Goldmann applanation tonometry and CCT before and 3, 6, 12, 18 and 24 months after surgery. RESULTS: CCT was a significant predictor of IOP only before PRK and 6 months after PRK (p < or = 0.05). The relation between IOP and CCT suggests corrections for CCT that are not clinically significant (0.81 mm Hg [standard error (SE) 0.33 mm Hg] and 1.00 mm Hg [SE 0.38 mm Hg] per 100 microns of corneal thinning preoperatively and at 6 months respectively). On average, there was a significant decrease in IOP after PRK (0.96 mm Hg and 1.24 mm Hg at 12 and 24 months respectively) (p < 0.05). There was a significant correlation between change in IOP and change in CCT (decrease of 2.1 mm Hg per 100 microns of corneal thinning) (p < 0.05). For a given change in CCT, individual changes in IOP were variable, with increases or decreases of more than 5 mm Hg in some cases. CONCLUSIONS: There are individual differences in IOP changes following PRK. Until further data are available we propose that the change in IOP between the preoperative visit (or the fellow eye, if healthy or untreated) and the 12-month visit be used as an individual correction factor to be applied to IOP measurements in the operated eye.

Adolescent↗
PubMed1998

Topical versus intravenous administration of tranexamic acid: a comparison of intraocular and serum concentrations in the rabbit.

BACKGROUND: Tranexamic acid has been shown to greatly reduce the incidence of secondary hemorrhage when administered orally or intravenously. Topical administration of the drug should result in much lower serum concentrations, with fewer adverse effects. We performed a study to determine whether topical application of tranexamic acid would yield higher intraocular concentrations and lower serum concentrations of drug than intravenous administration. METHODS: Ten New Zealand white rabbits received 25 mg/kg of tranexamic acid intravenously every 8 hours for 3 days. Another group of 10 rabbits received one drop (0.05 mL) of commercially available tranexamic acid solution (100 mg/mL) every 8 hours for 3 days to one eye. Tranexamic acid levels in the aqueous humour, vitreous humour and serum 1 hour after administration of the last dose of drug were determined. RESULTS: Analysis of variance showed that aqueous concentrations of tranexamic acid were significantly higher with topical delivery than with intravenous administration (15 vs. 9 micrograms/mL)(p < 0.05). Serum concentrations were significantly lower following topical administration (9 vs. 19 micrograms/mL)(p < 0.01). The drug was not detected in the vitreous humour in either group. INTERPRETATION: Topical delivery of tranexamic acid may prove to be valuable in yielding therapeutic intraocular concentrations of drug in patients with hyphema while minimizing systemic toxicity.

Administration, Topical↗
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↗