Purpose To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans. Methods We used novel SEM and UBM techniques to visualize the anterior, intermediate and posterior vitreous zonule and their connections to the ciliary body, vitreous membrane, lens capsule and ora serrata, and to characterize their age-related changes and correlate them with loss of accommodative forward movement of the ciliary body. We injected α-chymotrypsin focally to lyse the vitreous zonule and determined the effect on movement of the accommodative apparatus in monkeys. Results The vitreous attaches to the peripheral lens capsule and the ora serrata directly. The pars plana zonule and the posterior tines of the anterior zonule are separated from the vitreous membrane except for strategically placed attachments, collectively termed “vitreous zonule,” that might modulate and smooth the forward and backward movements of the entire system. Age-dependent changes in these relationships correlated significantly with loss of accommodative amplitude. Lysis of the intermediate vitreous zonule partially restored accommodative movement. Conclusions The vitreous zonule system may help to smoothly translate to the lens the driving forces for accommodation and disaccommodation generated by the ciliary muscle, while maintaining visual focus and protecting the lens capsule and ora serrata from acute tractional forces. Stiffening of the vitreous zonular system may contribute to age-related loss of accommodation and offer a therapeutic target for presbyopia.
Our findings quantify the movements of the zonule and ciliary muscle during accommodation, and identify their age-related changes that could impact the optical change that occurs during accommodation and IOL function.
Noninferiority trials are clinical studies designed to demonstrate that an investigational drug is at least as effective as an established treatment within a predetermined margin. They are conducted, in part, because of ethical concerns of administering a placebo to veterinary patients when an established effective treatment exists. The use of noninferiority trial designs has become more common in veterinary medicine with the increasing number of established veterinary therapeutics and the desire to eliminate potential pain or distress in a placebo-controlled study. Selecting the appropriate active control and an a priori noninferiority margin between the investigational and active control drug are unique and critical design factors for noninferiority studies. Without reliable historical knowledge of the disease response in the absence of treatment and of the response to the selected active control drug, proper design and interpretation of a noninferiority trial is not possible. Despite the appeal of conducting noninferiority trials to eliminate ethical concerns of placebo-controlled studies, there are real limitations and possible ethical conundrums associated with noninferiority trials. The consequences of incorrect study conclusions because of poor noninferiority trial design need careful attention. Alternative trial designs to typical noninferiority studies exist, but these too have limitations and must also be carefully considered.
The goal was to determine the age-related changes in accommodative movements of the lens and ciliary body in rhesus monkeys. Varying levels of accommodation were stimulated via the EdingerWestphal (E-W) nucleus in 26 rhesus monkeys, aged 6-27 years, and the refractive changes were measured by coincidence refractometry. Centripetal ciliary process (CP) and lens movements were measured by computerized image analysis of goniovideographic images. Ultrasound biomicroscopy (UBM) at 50 MHz was used to visualize and measure accommodative forward movements of the ciliary body in relation to age, accommodative amplitude, and centripetal CP and lens movements. At ∼3 diopters of accommodation, the amount of centripetal lens movement required did not significantly change with age (p=0.10; n=18 monkeys); however, the amount of centripetal CP movement required significantly increased with age (p=0.01; n=18 monkeys), while the amount of forward ciliary body movement significantly decreased with age (p=0.007; n=11 monkeys). In the middle-aged animals (12-16.5 years), a greater amount of centripetal CP movement was required to induce a given level of lens movement and thereby a given level of accommodation (p=0.01), compared to the young animals (6-10 yrs). Collectively, the data suggests that, with age, the accommodative system may be attempting to compensate for the loss of forward ciliary body movement by increasing the amount of centripetal CP movement. This, in turn, would allow enough zonular relaxation to achieve the magnitude of centripetal lens movement necessary for a given amplitude of accommodation.
The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.
Purpose-To determine if repeated intramuscular ketamine in monkeys on consecutive days affects intraocular pressure (IOP), and if the ketamine-induced IOP change has any relationship to systemic dehydration and/or changes in mean arterial pressure (MAP) of the animals.Methods-Nine monkeys were studied per 4 protocols. IOP was determined hourly for 6-hrs by Goldmann tonometry under ketamine anesthesia on 3 (protocol 1) or 5 (protocols 2 and 3) consecutive days, or on alternating days 1, 3 and 5 (protocol 4). Monkeys in protocols 3 and 4, but not in protocols 1 and 2, received subcutaneous Ringer's fluids at the end of each 6-hr session on days 1-4 or 1, 3 and 5; monkeys in protocols 2 and 3 received intravenous fluid infusion throughout the experiment on day 5. In protocols 2-4, MAP was measured hourly following each IOP measurement.Results-Monkeys receiving ketamine but no Ringer's fluids in protocol 1 or 2 showed significant IOP declines on days 2-3 or 2-4. The IOP declines were greater in magnitude in protocol 1 than in protocol 2. Daily subcutaneous Ringer's fluids appeared to delay IOP declines in protocol 3. Continuous intravenous fluid infusion on day 5 variably prevented IOP declines in protocols 2 and 3. Monkeys receiving ketamine and subcutaneous fluids on alternate days in protocol 4 showed no decline in IOP. No significant relationship between IOP and MAP was observed.Conclusions-Anesthesia induced by repeated intramuscular ketamine on consecutive days may produce significant IOP declines. Systemic dehydration during the anesthesia seems to be the predominant factor contributing to the IOP reduction. However, inter-individual differences in monkeys indicate that multiple factors may be involved. This study also suggests that fluid supplementation plus alternating anesthesia with recovery days may prevent IOP reduction in monkeys resulting from daily-prolonged ketamine anesthesia.
The unpredictable course followed by severe, chronic, non-healing wounds not only restricts the daily activities of affected patients, but also impairs their quality of life (QOL). Hyperbaric oxygen therapy (HBOT) treatment for such wounds elevates tissue oxygen content, increases cellular repair functions and the probability of wound healing, and improves the patient's QOL. This was a longitudinal, prospective study, and used a purposive sampling method. A total of 15 patients receiving HBOT at a medical center were enrolled. Data were collected by questionnaire before and after HBOT. The questionnaire included basic patient characteristics, self-perceived wound severity, wound physiological indices, and a QOL scale. The overall QOL score of the subjects after HBOT was higher than before HBOT. After HBOT, there was a positive correlation between the QOL of patients with problem wounds and the scoring of the Strauss wound classification system. After HBOT, there was a negative correlation between the QOL of patients with problem wounds and their self-perceived severity of the wound. The results were then used to provide suggestions for nursing care and additional research directions in order to effectively assist patients with problem wounds receiving HBOT, with the goal of achieving an optimal QOL.
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