OPA1 increases the risk of normal but not high tension glaucoma.

BACKGROUND: Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma. METHODS: 137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c-->t and IVS8+32t-->c) and exon 4 (c.473A-->G) of the OPA1 gene were genotyped in the study group. In addition, the entire OPA1 coding region was sequenced in 24 individuals with the CT/TT compound genotype using standard BigDye chemistries. RESULTS: There was no difference in either allele or genotype frequency for the IVS8+32t-->c single-nucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c-->t and the risk of developing NTG (OR=2.04, 95% CI=1.10 to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at IVS8+4 and IVS8+32 with NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001). CONCLUSIONS: The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.

Nurse prescribing in glaucoma.

AIMS/PURPOSE: To investigate a nurse-led assessment clinic of new referrals of possible glaucoma. To determine the potential for nurse prescribing. To review the background literature about nurse prescribing. METHODS: Audit of the outcomes of patients attending the nurse-led glaucoma assessment clinic during two defined periods (169 patients). An audit of all patients started on timolol or latanoprost treatment by a nurse following a protocol. RESULTS: A total of 46 patients were commenced on treatment at the clinic, 31 on timolol, 14 on latanoprost, and one on brimonidine. Four of these had the treatment stopped at the review clinic in order to reassess the diagnosis. Four patients in the timolol group developed side effects requiring a change in medication, but these could not have been predicted from their past medical history. Nine patients had treatment changed or added to because the intraocular pressure was felt to be inadequately controlled. During the two 3-month audits, a further 11 patients were commenced on treatment for glaucoma at the review clinic. CONCLUSIONS: Initial data from this clinic suggest that nurses possess the diagnostic skills necessary to prescribe for new glaucoma patients. The legal and administrative frame works are developing for more nurses to be able to prescribe. With the newer prostaglandin treatments for glaucoma being available, nurses may usefully and safely be able to prescribe first-line treatments for glaucoma.

Apparent glaucomatous visual field defects caused by dermatochalasis.

We have studied the effects of dermatochalasis on Humphrey automated perimetry of the central 24 degrees visual field. Fifteen visual fields of 9 ocular hypertensive patients (18 eyes) were found to be incongruous with their apparently healthy optic discs. Examination revealed dermatochalasis, which was felt to be responsible for the field defects. This was confirmed by reversal of the defects on repeating the field test (programme 24-2) with the redundant upper lid skin taped up, or in 2 cases following blepharoplasty. The defects always involved the superior visual field. The deepest and largest defects were sited in the supero-temporal quadrant in 13 of the 15 affected fields and the supero-nasal quadrant in 2 fields. The most common pattern was a temporally skewed defect which reflected the tendency of the loose upper lid skin to be greater in extent temporally than nasally. In 7 fields the supero-temporal defect extended to fuse with the blind spot, mimicking a superior arcuate scotoma. Temporal extension of the field defects below the horizontal meridian occurred in 5 fields. In cases where visual field testing was repeated without taping up the lid inter-test fluctuation in scotoma size and depth was observed, although the position of scotomas when present within the visual field remained constant. We conclude that dermatochalasis has the potential to confound diagnostic automated visual field testing for glaucoma.

Retinal venous sheathing and the blood-retinal barrier in multiple sclerosis.

OBJECTIVE: To assess the temporal relations among retinal appearance, disruption of the blood-retinal barrier, clinical subgroup, disease course, and disruption of the blood-brain barrier in multiple sclerosis. DESIGN: A 6-month prospective study involving monthly clinical ocular examinations, color fundus photography, fundus fluorescein angiograms, and magnetic resonance brain scans with gadolinium-diethylenetriamine-pentaacetic acid (Gd-DPTA) enhancement. SETTING: University-based ophthalmology and neurology departments. PATIENTS: Twenty-three patients with relapsing-remitting, primary-progressive, or secondary-progressive multiple sclerosis. RESULTS: Retinal venous sheathing was seen in six patients. The appearances observed included focal venous sheathing, diffuse venous sheathing, sheathing centered on sites of arteriovenous crossover, and focal perivenous hemorrhage. Arteriolar sheathing was also observed in one patient. Venous leakage on fundus fluorescein angiogram was detected in three patients, all of whom also had sheathing. The following three patterns of disruption of the blood-retinal barrier were seen on fundus fluorescein angiogram: focal leakage, extensive leakage, and very late wall staining. In one patient, the leakage was transitory. No correlations were observed between ophthalmologic features and multiple sclerosis clinical subgroup, disease course, or the number of new (Gd-DTPA-enhancing) lesions on magnetic resonance imaging. CONCLUSIONS: Disruption of the blood-retinal barrier, like the more frequent disruption of the blood-brain barrier seen on magnetic resonance imaging, is often unrelated to clinical neurologic relapses and occurs with apparently similar frequency in different patients independent of clinical disease course.

Determining progressive visual field loss in serial Humphrey visual fields.

PURPOSE: To evaluate the three commercially available computerized statistical algorithms for determining progression of glaucomatous field loss in serial Humphrey fields. METHODS: Serial Humphrey fields of 102 ocular hypertensive and glaucomatous eyes were analyzed by linear regression analysis of Statpac, glaucoma change probability and Progressor Programme, and the results compared with a retrospectively determined clinical outcome. RESULTS: Linear regression analysis of Statpac identified progression in 11 field series, glaucoma change probability identified progression in 23 field series, and Progressor Programme identified progression in 27 field series. Clinical outcome identified much less-progression than any of the three algorithms, determining that only seven eyes showed deterioration. There was a wide variation of results from analysis of the same group of field series by the three different algorithms. In contrast to the other two algorithms, which detected progression in similar percentages of both ocular hypertension and glaucoma field series. Progressor Programme detected progression predominantly in glaucoma field series. CONCLUSIONS: There was a high degree of variability among the three different algorithms for determining visual field progression, and none of them correlated well with clinical impression.

Chronic granulomatous anterior uveitis associated with multiple sclerosis.

A retrospective review is presented of the medical records of seven female patients with uveitis associated with definite multiple sclerosis. Six of the patients had severe bilateral chronic granulomatous anterior uveitis, which in four cases resulted in extensive posterior synechiae and scarring of the peripupillary iris. One patient had bilateral intermediate uveitis with unilateral posterior synechiae. Severe chronic granulomatous anterior uveitis associated with multiple sclerosis has a predilection for women, can precede neurological symptoms and can be controlled with topical steroids.

The prevalence of diabetic retinopathy and maculopathy and their risk factors in the non-insulin-treated diabetic patients of an English town.

A total population study of the ocular status of all known non-insulin-treated diabetic patients resident in the English town of Melton Mowbray has been conducted. The population prevalence of non-insulin-treated diabetes in the town was 6.7/1000. There were 215 patients in the target population, with 65% of the resident survivors participating in the study. Further data on ocular status were gathered from hospital records, bringing the total percentage for whom some information on ocular status was available to 74%. Corrected Snellen acuity was 6/12 or better in 76% of patients and the over-all prevalence rate for any diabetic retinopathy was 52%, for proliferative retinopathy was 4%, and for maculopathy requiring treatment was 10%. In a multivariate analysis, risk factors for retinopathy and/or maculopathy included longer diabetic duration, female sex, higher blood pressure, the use of anti-hypertensive drugs and cigarette smoking.

The preparation and characterisation of 111In-labelled 791T/36 monoclonal antibody for tumour immunoscintigraphy.

The anti-human tumour monoclonal antibody 791T/36 was conjugated to the cyclic dianhydride of DTPA and radio-labelled with 111In. The labelling method proved to be both simple and reliable and would be suitable for routine clinical use. Subsequent characterisation of this radio-pharmaceutical in vitro and in tumour-bearing hosts gave a strong indication as to its suitability for clinical tumour localisation studies.