Mechanisms of Subretinal Fluid Resorption in the Cat Eye

Small, non-rhegmatogenous retinal detachments (blebs) were made in cat eyes by injecting fluid into the subretinal space, and the time course of fluid resorption was monitored. Blebs made with Hanks' solution over the pigmented RPE resorbed 22% faster than those over the tapetum. Blebs made with a non-ionic solution (isotonic sucrose) took 43% longer to resorb than those made with Hanks' solution, and blebs containing 3 X 10~3 M sodium cyanide took 32% longer than controls. These results suggest that active ionic transport is involved in the absorption of subretinal fluid in the cat, as it is in the rabbit. Oncotic pressure in the choroid may also contribute to resorption, because blebs made with autologous serum took roughly 3 times longer to resorb than those made with non-proteinaceous Hanks' solution. The retinal vascular system does not appear to contribute, since the resorption time was similar for Hanks' blebs made under normal retina and those made under ischemic retina (produced by occluding retinal branch arteries with argon laser photocoagulation or endodiathermy). Invest Ophthalmol Vis Sci 27: [1560][1561][1562][1563] 1986 In our previous studies on subretinal fluid resorption in the rabbit, we found that both metabolic activity of the retinal pigment epithelium (RPE) and choroidal oncotic pressure contribute to the resorption of fluid from under experimental non-rhegmatogenous retinal detachments. We suspect that similar mechanisms exist in the human eye, judging by the fact that subretinal fluid can be absorbed very quickly from under a rhegmatogenous retinal detachment after sealing the retinal break. However, the human eye differs from the rabbit eye in that it has an intrinsic retinal vasculature which leaks fluid in various pathological conditions and, in theory, could also help to resorb fluid. In this paper, we report on the mechanisms of subretinal fluid resorption in an animal which has an intrinsic retinal vasculature, the cat. Our primary concerns were whether metabolic transport was involved and whether the intrinsic retinal vessels contributed to the removal of fluid. Materials and Methods These investigations adhered to the ARVO Resolution on the Use of Animals in Research. Cats weigh- ing 2.1-5.8 kg were anesthetized with 35 mg/kg pentobarbital administered intraperitonealy. The pupils were dilated with two drops of 1% cyclopentolate and 10% phenylephrine. The outer canthus was incised, and some of the lateral orbital bone removed to expose the temporal scleral surface, in which a 3 mm slit was made meridionally 5 mm posterior to the limbus. The basic technique for making detachments was identical to that used for rabbits

Recovery of retinal adhesion after enzymatic perturbation of the interphotoreceptor matrix. Invest Ophthalmol Vis Sci.

The retina adheres to the retinal pigment epithelium (RPE) and becomes detached only when forced by vitreous traction or fluid pressure in the subretinal space. Current evidence suggests that retinal adhesiveness depends on several complementary, and possibly interactive, systems, 1 including anatomic interdigitation between photoreceptor outer segments and RPE microvilli, Recent work has shown that the molecular constituents of the IPM are not distributed homogeneously. There is evidence that domains of IPM glycoconjugates exist and are associated with both rod and cone photoreceptor cells and with the apical surface of the RPE. 10 Domains of IPM associated with cone photoreceptors, termed "cone matrix sheaths," are composed of aqueous-insoluble proteoglycans containing chondroitin 6-sulfate and O-glycosidically linked oligosaccharides that bind peanut agglutinin (PNA). ' 11 By contrast, the oligosaccharides associated with rod photoreceptor-associated IPM proteoglycans appear to have terminal sialic acid residues that prevent the binding of PNA. 101213 Although the precise function of most IPM constituents is unknown, recent studies provide evidence that some aqueous-insoluble proteoglycans participate in retinal adhesion. 16 For example, we demonstrated recently 9 that retinal adhesion is weakened significantly by exposure of the IPM to specific degrading enzymes in vivo. Neuraminidase type X and chondroitinase ABC both weakened adhesion, but each affected the matrix differently, as shown by lectin cytochemistry and immunocytochemistry. These experiments provided evidence that IPM glycoconjugates participate in retinal adhesion, but they raised questions about which components are critical in the adhesive process and whether reestablishment of their normal distribution is associated with restoration of retinal adhesiveness. In this study, we investigated the recovery of retinal adhesion after enzyme treatment, relative to the recovery of the normal distribution of PNA-binding glycoconjugates in the IPM. We also evaluated, by electroretinography (ERG) and light microscopy, whether long-term retinal or RPE damage results from enzyme treatment

Interleukin(IL)-1/IL-6-inhibitor-associated drug reaction with eosinophilia and systemic symptoms (DReSS) in systemic inflammatory illnesses.

BACKGROUND: After introducing interleukin(IL)-1/IL-6 inhibitors, some Still and Still-like patients developed unusual often fatal pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: We sought to facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not-stopping IL-1/IL-6-inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6-inhibitors to 37 cases not-stopping these drugs. RESULTS: Before reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease onset age for reaction cases with pre-existing cardiothoracic comorbidities. After reaction began, increased rates of pulmonary complications and macrophage activation syndrome (MAS), differentiated drug-reaction cases from drug-tolerant controls (p=4.7x10 CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6-inhibitors significantly improved outcomes

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. Methods: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. Results: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. Discussion: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal