Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration

PURPOSE. To investigate the effects of a hereditary retinal degeneration on retinal oxygenation and determine whether it is responsible for the severe attenuation of retinal circulation in hereditary photoreceptor degenerations. METHODS. Seven adult Abyssinian cats affected by hereditary retinal degeneration were studied. Oxygen microelectrodes were used to collect spatial profiles of retinal oxygenation in anesthetized animals. A one-dimensional model of oxygen diffusion was fitted to the data to quantify photoreceptor oxygen utilization (QO 2 ). RESULTS. Photoreceptor QO 2 progressively decreased until it reached zero in the end stage of the disease. Average inner retinal oxygen tension remained within normal limits at all disease stages, despite the observed progressive retinal vessel attenuation. Light affected photoreceptors normally, decreasing QO 2 by ϳ50% at all stages of the disease. CONCLUSIONS. Loss of photoreceptor metabolism allows choroidal oxygen to reach the inner retina, attenuating the retinal circulation in this animal model of retinitis pigmentosa (RP) and probably also in human RP. As the degeneration progresses, there is a strong relationship between changes in the a-wave of the ERG and changes in rod oxidative metabolism, indicating that these two functional measures change together. 2-6 We hypothesized that the pronounced vasoconstriction results from decreased oxygen utilization by the outer retina after photoreceptor loss. Because less choroidal oxygen is used by the photoreceptors, it should reach the inner retina, where oxygen is known to cause constriction of retinal vessels. 10 Vessels do not simply constrict. Eventually they are lost in animals with photoreceptor degenerations. 6 These studies suggest not only a physiological role of oxygen, but a trophic (or antitrophic) one as well. In the present study, we further examined the hypothesis that oxygen from the choroid is responsible for attenuation of the retinal circulation, by characterizing changes in retinal oxygenation and oxidative metabolism during the progression of a feline hereditary retinal degeneration in a colony of Abyssinian cats. 3 The autosomal recessive genetic defect in this animal is not yet known, but it exhibits a slow rod-cone degeneration similar to human RP. Using measurements of intraretinal oxygen tension (PO 2 ) in these animals and our mathematical model of oxygen diffusion and utilization, 13 A preliminary report of these results has been presented (Linsenmeier RA, et al. IOVS 2000;41:ARVO Abstract 4721). METHODS Animals Eight Abyssinian cats affected by a hereditary retinal degeneration were studied. These are the same cats in which an ERG study, reported in this issue, was also performed. 13 3,13 The hematocrit from one stage 3 animal was low because of surgical complications and continued to decrease during the experiment. In this animal, the earlier choroidal PO 2 and the inner retinal PO 2 , which were in the normal range, are included in the reported data, but oxygen consumption data and later choroidal PO 2 data from this animal were not used. Electrode problems prevented data collection in one stage 2 animal. Data from animals with retinal degeneration were compared to similar data obtained from normal cats

Quality of Life Assessment of Chronic Thyroid Eye Disease (TED) Patients in the United States

TED is an orbital autoimmune disease that causes pain, dysmotility, vision-impairment, facial alterations and other debilitating sequelae. Although improvement can occur as inflammation subsides, patients often have persistent discomfort, tearing, diplopia, and facial disfigurement that includes proptosis and eyelid retraction. These sequalae can severely impact quality of life (QOL).1-3 The current survey examined QOL in 100 chronic US TED patients

A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings

Objective To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect