A triad of retinal signs in Alport syndrome: The 'stair-case' fovea, choroidal thinning and peripheral schisis.

BACKGROUND: Alport syndrome is an inherited Type IV collagenopathy characterised by renal failure, hearing loss and ophthalmic manifestations such as lenticonus and dot-and-fleck retinopathy. New signs have been described which can be useful both for diagnosis and for prognosticating the risk of complications. This study examines and describes a triad comprising the unusual 'stair-case' foveal sign, together with choroidal thinning and late-stage peripheral schisis in a patient with Alport syndrome. CASE PRESENTATION: This is a case report of a 49-year-old Caucasian male with a background of X-linked Alport syndrome presenting with gradual and progressive diminution of vision in the left eye with a central blur. He had already undergone three renal allografts, was deaf and suffered from hypertension by the time of his first presentation to ophthalmology. On examination, corrected visual acuity was 6/9.5 in the right eye and 6/30 in the left eye. Optical coherence tomography imaging showed an unusual 'stair-case' sign of the fovea in both eyes, together with choroidal thinning. We postulate that an abnormal vitreomacular interface followed by vitreomacular traction and eventually separation, removing layers of the inner retina with the vitreous, led to this unusual appearance. Subsequently, this patient also developed schitic changes more peripherally in the retina which progressed over the following 5 years. CONCLUSION: The stair-case foveal sign, choroidal thinning and mid-peripheral schisis are three signs that clinicians might expect to encounter on optical coherence tomography imaging of patients with Alport syndrome. These findings can be attributed to unique mutations of collagen IV which lead to a variety of clinical phenotypes affecting basement membrane structures. Identification of these features may not only be useful diagnostically and in forecasting complications such as macular holes, but also predict mode of inheritance and likelihood of early-onset renal failure.

Contact lens prescribing in a specialist medical contact lens clinic based in an NHS hospital: an audit of changing practice.

PURPOSE: To describe the range of indications for contact lenses and the types of lenses being used in an NHS hospital-based specialist medical contact lens clinic and contrast this with information from 12 years ago. METHODS: A retrospective audit of 596 clinic attendances was performed in the contact lens clinic at the Western Eye Hospital between April 2002 and March 2003. The results were compared with a similar audit performed in 1991. We used the hospitals electronic records, and information on contact lens prescribing was obtained directly from the receipts generated by the contact lens department and the accounts department. RESULTS: We saw 392 patients with 88.5% of patients requiring 2 or less visits per year. The majority of referrals are for high myopia (28.6%) closely followed by aphakia (25.2%) and keratoconus (24.7%). This is in contrast to 1991 when 68% of referrals were for aphakia and twice as many myopes (17%) were seen as keratoconus patients (8%). A total of 560 lenses were prescribed with 68 different types of lens in use. The seven most commonly used lens types accounted for 61% of all lenses prescribed. CONCLUSIONS: Medical contact lens clinics provide a specialist service and also provide an important training resource for junior ophthalmologists. Safer cataract surgical techniques have had a significant impact on the case mix seen in our clinic, with the emphasis moving away from aphakic and myopic patients and toward the more challenging to fit eyes with keratoconus or postcorneal surgery.

Steroid-responsive HIV optic neuropathy.

A 37-year-old man with bilateral optic neuropathy who recovered on steroid treatment is described. He was subsequently found to be human immunodeficiency virus 1 (HIV-1) positive prior to the onset of his visual symptoms, and no other cause of his optic neuropathy could be found. There is some evidence that HIV itself may be a cause of symptomatic optic neuropathy. A spontaneously relapsing and remitting multiple sclerosis-like syndrome has previously been described in HIV-positive patients, and this may present with optic neuritis. A chronic optic neuritis in HIV-positive patients that is not usually symptomatically important has also been described. We review the literature related to these topics and our patient.

Granular cell tumour of the spinal cord in a patient with Rubenstein-Taybi syndrome.

A case of cervical spinal cord granular cell tumour in a patient with Rubenstein-Taybi syndrome is described. A granular cell tumour arising from the spinal cord itself has never been previously described. Complete excision of the tumour could not be achieved owing to its location. It subsequently recurred and was treated with radiotherapy. The patient made a complete recovery with no further recurrence after 2 years of follow-up.

Hypolipidaemic properties of a potent and bioavailable alkylsulphinyl-diphenylimidazole ACAT inhibitor (RP 73163) in animals fed diets low in cholesterol.

RP 73163 ((S)-2-[5-(3,5-dimethyl-l-pyrazolyl)pent-l-yl)-sulphinyl]-5, 6-diphenylimidazole) has been shown to be a potent and specific inhibitor of acyl-CoA:cholesterol acyltransferase (EC 2.3.1.26; ACAT) in vitro using the tissues of experimental animals as sources of the enzyme. The concentrations of RP 73163 required to produce 50% inhibition of ACAT activity (IC50 values) in microsomal preparations ranged from 86 nM for rat liver to 370 nM for rabbit intestine. In whole cell assays using human hepatic (HepG2), intestinal (Caco2), and monocytic (THP-1) cell lines, RP 73163 inhibited ACAT activity with IC50 values of 266, 158, and 314 nM, respectively. The addition of RP 73163 (0.03-1.0 microM) to the medium of cultured HepG2 cells produced a concentration-dependent decrease in apolipoprotein B (apoB) secretion. The compound has high systemic bioavailability. Using a bioassay, a concentration of active inhibitor equivalent to 29 microM of parent compound was present in plasma 1 hr after oral administration of RP 73163 (50 mg.kg-1). In rats that had been fed a basal diet ad libitum or starved for 18 hr prior to blood sampling, the administration of RP 73163 (50 mg.kg-1 b.i.d. for 7 days) reduced plasma triglyceride levels by 50% without affecting the concentration of cholesterol. This hypotriglyceridaemic effect was associated with reductions in plasma very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) levels. RP 73163 decreased the rate of VLDL secretion by 24% in Triton WR-1339-treated rats that had been fasted overnight but did not affect the secretion rate in animals fed ad libitum, indicating that ACAT was only important in regulating VLDL secretion under certain nutritional conditions. RP 73163 reduced the accumulation of intraperitoneally administered [3H]leucine into the plasma VLDL-apoB pool in both fed and fasted states. The results suggest that, in fed animals at least, an increase in the clearance of VLDL from the bloodstream may contribute to the hypolipidaemic activity of the compound. In rabbits with casein-induced endogenous hypercholesterolaemia, RP 73163 specifically reduced the levels of cholesterol carried by LDL. In conclusion, the hypolipidaemic actions of RP 73163, a potent and systemically bioavailable ACAT inhibitor, are consistent with a reduction in the secretion of apoB containing lipoproteins by hepatic tissue and possibly with an increase in the clearance of these particles.

RP 64477: a potent inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase with low systemic bioavailability.

RP 64477 (N-butyl-3-(p-decyloxybenzamido)-4-(methylthio)benzamide) has been shown to be a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) in intestinal, hepatic, adrenal, and arterial tissue preparations obtained from a range of animal species. Drug concentrations producing 50% inhibition of enzyme activity (IC50 values) ranged from 14-283 nM. Inhibition by RP 64477 in a rabbit intestinal enzyme preparation was shown to be non-competitive with respect to the substrate oleoyl-CoA. In whole cell assays using human intestinal (CaCo-2), hepatic HepG2) and monocytic (THP-1) cell lines, RP 64477 inhibited ACAT activity with IC50s of 113, 503, and 180 nM, respectively. RP 64477 (0.03% w/w by diet) reduced significantly cholesterol absorption in cholesterol/cholic acid-fed rats from 94+/- 8% to 65 +/- 4%. In cholesterol-fed rabbits, cholesterol absorption was reduced from 72 +/- 5% to 50 +/-5% and 44 +/- 5% at dose levels of 10 and 30 mg kg-1 b.i.d., respectively. Plasma cholesterol levels were reduced dose-dependently in both cholesterol/cholic-acid-fed rats and cholesterol-fed rabbits. Neither cholesterol absorption nor plasma cholesterol levels were reduced significantly in animals maintained on standard laboratory diets. Pharmacokinetic studies indicated that RP 64477 were very poorly absorbed following oral administration to rats. Plasma levels of drug were < 2 ng mL-1 following a dose of 2000 mg kg-1 p.o.. When radiolabelled RP 64477 was administered orally, limited absorption was indicated by the overwhelming elimination of radioactivity in the faces (96.4% of administered material) coupled with low renal clearance (0.6% of dose) and biliary excretion (0.05% of dose). In conclusion, this work shows that RP 64477 is a potent inhibitor of ACAT obtained from a range of animal species and man. Inhibition of cholesterol absorption and hypocholesterolaemic activity has been demonstrated in rats and rabbits maintained on diets supplemented with cholesterol. Pharmacokinetic studies indicate low systemic exposure to RP 64477 as a result of limited absorption of this drug.

Aortic root replacement and extraanatomic bypass for interrupted aortic arch in an adult.

We describe an unusual case of interrupted aortic arch, aneurysmal ascending aorta, and aortic regurgitation in a 24-year-old man. He presented with general malaise, weakness of his legs, and hypertension. A single-stage operation was performed in which the aortic root was replaced with concomitant extraanatomic bypass of the interrupted segment of the aortic arch. He made a full recovery and has returned to work.