The acute morphologic changes that occur at the optic nerve head induced by medical reduction of intraocular pressure.

PURPOSE: The mechanical theory of glaucoma postulates that raised intraocular pressure (IOP) causes laminar distortion resulting in damage to axons at the optic nerve head. There is some evidence that the change in morphology may occur over a short time course. The aim of this paper was to detail the acute morphologic changes at the optic nerve head when IOP was lowered with medical therapy in a clinical population. METHODS: Subjects referred to the glaucoma clinic that had a documented IOP of over 28 mm Hg, on no treatment, in one or both eyes were included. Tonometry, pachymetry, and scanning laser ophthalmoscopy were performed before and after lowering IOP with topical apraclonidine and oral acetazolamide. The significance of change in outcome variables was assessed using a paired t test allowing for dependence within subjects and, for sensitivity, with a nonparametric Wilcoxon signed-rank test. RESULTS: Data were obtained from 38 eyes of 19 patients with a mean age of 67 years. After lowering IOP for only 1 hour, there was a significant decrease in mean cup volume (mean change in volume below surface 26.8 microm3, P< or =0.001) and mean cup depth (13.8 microm, P<0.01), there being a corresponding increase in mean rim area (37.3 microm2, P<0.034). There was no statistically significant change in central corneal thickness after administration of the IOP lowering medications. CONCLUSIONS: In the present study, it was shown that acute and statistically significant alterations in optic disc morphology occur when IOP is lowered medically with a combination of topical apraclonidine and systemic acetazolamide. The technique, therefore, may be useful to further investigate subgroups of glaucomatous eyes and test etiologic hypotheses.

Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms.

Stickler syndrome due to mutations in COL2A1 is usually the result of premature termination codons and nonsense mediated decay resulting in haploinsufficiency of type II collagen. Here we present two missense mutations and one apparently silent mutation that each result in Stickler syndrome, but via different molecular mechanisms. One alters the translation initiating ATG codon. The second mutation is a unique glycine substitution in the minor collagen helix of the procollagen. To our knowledge a glycine substitution has not previously been reported in this region of fibrillar procollagens. The third mutation appears to be a silent change altering a GGC codon to GGT both for glycine, but use of a splicing reporter assay demonstrates that it results in missplicing and a shift in the reading frame.

Significant ocular findings are a feature of heritable bone dysplasias resulting from defects in type II collagen.

BACKGROUND/AIMS: The type II collagenopathies are a phenotypically diverse group of genetic skeletal disorders caused by a mutation in the gene coding for type II collagen. Reports published before the causative mutations were discovered suggest heritable bone dysplasias with skeletal malformations may be associated with a vitreoretinopathy. METHODS: A retrospective notes search of patients with a molecularly characterised type II collagenopathy chondrodysplasia who had been examined in the ophthalmology clinic was conducted. RESULTS: 13 of 14 patients had a highly abnormal vitreous appearance. One patient aged 11 presented with a total retinal detachment. Two other children aged 2 and 4 had bilateral flat multiple retinal tears on presentation. 10 of 12 patients refracted were myopic. Two patients had asymptomatic lens opacities: one associated with bilateral inferiorly subluxed lenses and the other with a zonule and lens coloboma. CONCLUSION: Heritable skeletal disorders resulting from a mutation in the gene coding for type II collagen are associated with abnormal vitreous, myopia and peripheral cataract with lens subluxation. In bone dysplasias resulting from a defect of type II collagen there is likely to be a high risk of retinal detachment with a propensity to retinal tears at a young age.

Clinical characterisation and molecular analysis of Wagner syndrome.

AIM: To detail the clinical findings in a British family with molecularly characterised Wagner syndrome. BACKGROUND: Only in the last year has the specific genetic defect in Wagner syndrome been identified, and the background literature of the molecular genetics is outlined. Clinical and laboratory findings in a second case of Wagner syndrome are included to highlight difficulties that can be encountered when identifying pathogenic mutations for disorders arising in complex genes. METHODS: Mutation screening was performed using PCR and RT-PCR. RESULTS: A heterozygous mutation was found converting the donor splice site of exon 8 of the chondroitin sulphate proteoglycan 2 (CSPG2). This is the same mutation that has been reported in the original Wagner pedigree. The main clinical features of Wagner syndrome are vitreous syneresis, thickening and incomplete separation of the posterior hyaloid membrane, chorioretinal changes accompanied by subnormal electroretinographic responses, an ectopic fovea and early-onset cataract. A clinical feature present in this family, but previously undescribed, is anterior uveitis without formation of synechiae. Wagner syndrome has a progressive course, resulting in loss of vision even in the absence of retinal detachment. CONCLUSION: On a background of considerable confusion regarding the distinction between Wagner syndrome and predominantly ocular Stickler syndrome, it is now apparent the that two conditions are both clinically and genetically distinct. This report summarises the clinical findings in Wagner syndrome and extends the phenotypic characteristics.

Risk factors for posterior vitreous detachment: a case-control study.

PURPOSE: To identify possible risk factors for the development of posterior vitreous detachment (PVD). DESIGN: Retrospective case-control study. METHODS: A total of 138 cases with PVD and 114 age-matched controls were accrued from two different sites. Demographic, medical, ocular, and lifestyle data were obtained through chart review, questionnaires, and clinical examination. A 108-item semiquantitative food frequency questionnaire was also used to estimate macro- and micronutrient intake. Univariate and multivariate regression analyses were employed to identify variables significantly associated with the main outcome measure of PVD. Subgroup analysis of gender-specific variables was performed. RESULTS: Among all patients, multivariate regression analysis demonstrated female gender (odds ratio [OR] = 2.01, P = .016), myopic refraction (OR = 4.32, P < .0005), and higher intake of vitamin B6 (OR = 2.61, P = .001) to be associated with PVD after controlling for age. In the subgroup analysis of women, menopause (OR = 18.2, P < .0005), myopic refraction (OR = 3.42, P = .01), and higher intake of vitamin B6 (OR = 3.92, P = .005) were associated with PVD. Specifically, there was a significant association between vitamin B6 and PVD amongst premenopausal women but not amongst postmenopausal women. CONCLUSIONS: An association between PVD and menopause has not been documented previously. We suspect that high estrogen levels seen in premenopausal women may be protective against PVD and that hormonal changes associated with menopause may lead to changes in the vitreous, predisposing to PVD. Higher levels of intake of vitamin B6 were also associated with the development of PVD in premenopausal women possibly through an anti-estrogen effect. These findings should be investigated further with prospective studies.