Stochastic Pharmacokinetic-Pharmacodynamic Modeling for Assessing the Systemic Health Risk of Perfluorooctanoate (PFOA).

A phase 1 dose-escalation trial assessed the chemotherapeutic potential of ammonium perfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer patients who failed standard therapy received weekly APFO doses (50-1200 mg) for 6 weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured predose and weekly thereafter. Several clinical measures including total cholesterol, high-density lipoproteins (HDLs), thyroid stimulating hormone (TSH), and free thyroxine (fT4), relative to PFOA concentrations were examined by: Standard statistical analyses using generalized estimating equations (GEE) and a probabilistic analysis using probability distribution functions (pdf) at various PFOA concentrations; and a 2-compartment pharmacokinetic/pharmacodynamic (PK/PD) model to directly estimate mean changes. Based on the GEE, the average rates of change in total cholesterol and fT4 associated with increasing PFOA were approximately -1.2×10-3 mmol/l/µM and 2.8×10-3 pmol/l/µM, respectively. The PK/PD model predicted more closely the trends observed in the data as well as the pdfs of biomarkers. A decline in total cholesterol was observed, with a clear transition in shape and range of the pdfs, manifested by the maximum value of the Kullback-Leibler (KL) divergence, that occurred at plasma PFOA between 420 and 565 µM (175 000-230 000 ng/ml). High-density lipoprotein was unchanged. An increase in fT4 was observed at a higher PFOA transition point, albeit TSH was unchanged. Our findings are consistent with some animal models and may motivate re-examination of the epidemiologic studies to PFOA at levels several orders of magnitude lower than this study. These observational studies have reported contrary associations, but currently understood biology does not support the existence of such conflicting effects.

Trabeculectomy surgery augmented with intra-Tenon injection of mitomycin C.

PURPOSE: To describe a novel approach to mitomycin C (MC) application during trabeculectomy surgery and to report the 1-year results of surgery using this technique. METHODS: One hundred and eight consecutive trabeculectomies and phaco-trabeculectomies using MC were performed by a single consultant surgeon, using a standardized technique. This technique involved injecting MC into the Tenon's layer during the procedure, rather than applying it directly to the under-surface of the conjunctiva. RESULTS: Preoperative mean intraocular pressure (IOP) was 23.6 +/- 5.8 mmHg. Mean IOP 12 months following surgery was 12.2 +/- 3.9 mmHg. Seventy-six eyes (70.3%) had an IOP less than 2/3 listing IOP at 12 months without the need for anti-glaucoma medication. Ninety-three eyes (86%) had an IOP <21 mmHg, 79 (73%) had an IOP <16 mmHg and 62 (57%) had an IOP <14 mmHg without anti-glaucoma medication at 12 months. Transient complications included hyphaema, bleb leak and choroidal detachment in 14.8%, 5.6% and 15.7% of cases, respectively. Hypotony (defined as IOP <7 mmHg, excluding the first day postoperatively) was seen in 21.3% of cases. At 12 months, 21 eyes (19.4%) had cystic blebs and five (4.6%) had Tenon's cysts with an IOP greater than 20 mmHg. CONCLUSION: A novel means of applying intraoperative MC is described. The 12-month outcome data show it to be an effective technique that compares favourably with others in the literature.

Aggregations of retinal pigment epithelial cells on inferior retinal blood vessels, a clinical sign of early proliferative vitreoretinopathy.

PURPOSE: To determine the relationship between 'pigment clusters' on blood vessels (BvRPE) on the inferior retina in patients with rhegmatogenous retinal detachment, and existing proliferative vitreoretinopathy (PVR). METHODS: A prospective observational non-comparative study of consecutive patients presenting with rhegmatogenous retinal detachment to a tertiary referral university department was performed. The retina was inspected preoperatively for the detection of BvRPE. A relationship with existing PVR was determined. RESULTS: A total of 103 patients were recruited, 70 men and 32 women, mean age 56.7 years, with 57 left eyes. Mean duration of follow up was 9.2 months. Nineteen patients (18.4%) had BvRPE, and 20 had RPE clusters off blood vessels (nine had both). In those with the sign of BvRPE the mean number of RPE clusters on blood vessels was 5.7 (SD 5.8). The mean number of clock hours affected was 2.32 (SD = 1.58). Eight had B grade PVR and three C grade PVR. Patients with BvRPE were more likely to have PVR grades B or C than those without the sign (P = 0.002). The mean number of operations in those with the sign was 1.32 (SD = 0.58) and was statistically similar to those without BvRPE. Visual outcome was statistically similar in those with and without the sign. CONCLUSION: Patients with rhegmatogenous retinal detachment may demonstrate 'pigment clusters' on blood vessels in the inferior retina (BvRPE). This is likely to be a specific feature found in PVR and an early sign of activation of retinal pigment epithelial cells.

Anterior and posterior vitreous cysts.

Vitreous cysts are rare structural entities of uncertain aetiology. Although most do not produce troublesome visual symptoms, they can cause diagnostic difficulties in clinical practice. Two different types are described and the possible aetiologies of congenital and acquired vitreous cysts are discussed.