Efficacy would be a quantitative change in foveal cone function and possibly distal laminar structure. FST provides a subjective photoreceptor-based outcome; OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can provide objective measures of postretinal transmission. Minimal change over a decade indicates that there is no practical value in natural history studies.
Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.
BACKGROUND: Previous studies have suggested that administration of epidural 3% 2-chloroprocaine (CP) before epidural morphine results in decreased analgesic efficacy of epidural morphine. We sought to determine whether these observations were a result of antagonism or a window period between the conclusion of surgical anesthesia for cesarean delivery and the peak onset time of epidural morphine, and whether a method to preserve the analgesic efficacy of epidural morphine exists. METHODS: Term parturients scheduled for nonemergent, unscheduled cesarean delivery with preexisting labor epidural catheters were recruited for this exploratory, randomized, single-blinded, noninferiority trial. Subjects were randomized to initial dosing to a T4 dermatome surgical anesthetic level with either 3% CP or 2% lidocaine with 1:200,000 epinephrine and sodium bicarbonate (LEB). Subsequent redosing for both groups was performed with LEB at regular intervals. Epidural morphine 3 mg was administered to both groups after delivery. Assessing the difference between the 2 groups in total opioid use for the first 24 hours after epidural morphine administration was the primary objective. The noninferiority margin of 10 oral milligram morphine equivalents was prespecified based on previous noninferiority studies. Secondary end points included time from epidural morphine administration to first rescue opioid request, numerical pain scores, nausea/vomiting, and pruritus. RESULTS: Data were analyzed for 40 parturients, 20 in each group. The median 24-hour opioid consumption for the CP group was 0 (Q 1 = 0 and Q 3 = 15.6) oral milligram morphine equivalents compared to 15 (6.3-22.5) for the LEB group. The median difference was −7.5, with a 95% confidence interval −15 to 0. Noninferiority was concluded, as the confidence interval was less than the predetermined noninferiority margin of 10 oral milligram morphine equivalents. There was no treatment effect on time to first opioid request and no statistically significant differences in pain scores or nausea, vomiting, or pruritus at all time points (4, 8, 12, and 24 hours after epidural morphine administration). CONCLUSION: While designed as an exploratory study, initial epidural dosing with 3% CP and beginning subsequent redosing with LEB within 30 minutes of the initial CP bolus provided noninferior postcesarean analgesia with epidural morphine compared to initial epidural dosing and redosing with LEB. Previous observations of decreased analgesic efficacy of epidural morphine after epidural CP were likely due to a window period that may be mitigated by redosing with lidocaine; however, larger studies are necessary to confirm these findings.
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