Argon laser-induced retinal herniation.
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Biomedical subjects
Publications and source records attributed to S J Ryan.
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A research committee of the Association of University Professors of Ophthalmology disseminated a survey questionnaire to determine the state of research in departments of ophthalmology across the United States. The questionnaire contained 71 questions that were designed to assess attitudes and trends within members' departments and to solicit suggestions from the membership. Of the 145 members and affiliates queried, 140 responded. While the results of the survey indicate significant diversity among departments, departmental chairpersons view research as a major priority in the goals of their departments, and they envision maintenance or expansion of research over the next decade. The survey results have been collated and serve now as the basis for this Association of University Professors position article.
In proliferative vitreoretinopathy, macrophages and retinal pigment epithelial cells are associated with microfibrillar matrix proteins in the vitreous cavity, but the contribution of this extracellular matrix to the pathophysiology is not known. We used radiolabeling techniques on cultured human retinal pigment epithelial cells to correlate the secretion of extracellular matrix proteins with macrophage-induced modulation of cell proliferation and morphologic features. Retinal pigment epithelial cells incubated in a macrophage-conditioned medium assumed fibrocytelike morphologic characteristics, grew faster, and exhibited a decreased cellular release of fibrillar and nonfibrillar matrix components. However, due to a simultaneous greater increase in cell numbers in these modulated cultures, the total production of fibrillar and nonfibrillar matrix components by the culture population was increased.
This article describes the trial design and baseline results for the Silicone Study, a multicenter, randomized surgical trial designed to compare the effectiveness of silicone fluid versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR). Design features include (1) standardization of the surgical protocol to reduce intersurgeon variability, (2) formulation of a PVR clinical classification system relevant to modern vitreoretinal surgery, and (3) creation of a photographic protocol to document PVR pathology. Statistical issues affecting the analysis of the outcome data include (1) the addition of a second group of patients with more severely diseased eyes after the trial began, (2) the change to a different long-acting gas during the course of the trial, and (3) recurrent retinal detachments that require reoperations with the randomized treatment, and, in some instances, a crossover from the randomized to the alternate treatment. Demographic and baseline ocular characteristics are presented for the two groups under study.
The disciform response of age-related macular degeneration and other diseases is determined by the development of subretinal neovascularization (SRN). Experimental animal models of SRN based on disruption of Bruch's membrane have been studied extensively during the past decade. Argon laser photocoagulation-induced SRN in primates is one such model, but this is associated with extensive retinal damage. Because the injured retina could be angiogenic, and is not present in clinical SRN, this model might be more relevant if this factor could be eliminated. The current study was conducted with the primary aim of producing a rabbit model of SRN that minimizes retinal damage. Argon laser endophotocoagulation was applied beneath the retina of albino rabbits to achieve this goal. Although argon photocoagulation does not cause clinically apparent SRN (i.e., associated with leaking and pooling of fluorescein) in the rabbit, all laser lesions produced in the current study contained microscopic SRN. A rabbit SRN model would be highly desirable as a step toward other animal models, perhaps involving nonhuman primates, which might ultimately be clinically more relevant.
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We studied 41 eyes with acute retinal detachment after penetrating ocular trauma in a retrospective cohort analysis. Pars plana vitrectomy was performed in 28 eyes, while the remaining 13 eyes had only primary repair and closure of the wound. The two groups differed in the type of trauma (more gunshot wounds in the vitrectomy group and more blunt injuries in the nonvitrectomized group). Visual success (visual acuity of 5/200 or better) was observed in 10 (37%) of the eyes treated by vitrectomy compared with one (8%) of the eyes in the nonvitrectomy group. Anatomic success was achieved in 21 (75%) of the eyes in the vitrectomy group but in only one (8%) of those in the nonvitrectomy group. Enucleation or phthisis was observed in seven (54%) of the eyes in the nonvitrectomy group compared with only five (18%) in the vitrectomy group. Significant prognostic factors for anatomic outcome in the vitrectomy group were the location of the laceration and the presence of the lens.
A retrospective survey was done of all ocular and adnexal trauma cases seen at a large metropolitan hospital during a 6-month period. By determining patient demographics, causes of the eye injuries, and extent of ocular damage, the authors hoped to delineate areas where preventive measures might decrease such trauma. Demographic and clinical data on 1132 patients were analyzed. Most patients were in the first three decades of life and were male. Blunt trauma was the most common type of injury. Assault was the most common cause and accounted for the highest number of serious injuries. Eye injuries associated with violence are difficult to prevent using conventional strategies that are usually effective in the home and workplace.
We report the successful treatment of three cases of traumatic ruptures of the globe complicated by massive choroidal hemorrhage, uveal prolapse and retinal detachment. All three of the eyes were aphakic prior to injury and all patients were age 64 or older. The presenting visual acuity in all patients was light perception. The blunt injury in each case caused a wound dehiscence at the site of previous cataract extraction. All injuries were associated with uveal prolapse. Secondary surgical intervention was performed when the hemorrhagic choroidal detachments had decreased as demonstrated by echography in the suprachoroidal space, occurring at an average of 14 days after injury. The management consisted of surgical drainage of the choroidal hemorrhage combined with vitrectomy and silicone oil injection. Successful reattachment of the retina was achieved in all cases. Postoperative epiretinal membranes formed in two cases but all were anatomically successful at six months. Final visual acuities varied from 20/70 to 1/200, visual acuity being a function of secondary contusive damage to the retina and choroid. We believe that in eyes sustaining severe blunt injuries resulting in rupture of the globe complicated by massive choroidal hemorrhage and retinal detachment, properly timed external drainage of the choroidal hemorrhage combined with pars plana vitrectomy and silicone oil injection is a useful approach.
We investigated the role of the retinal pigment epithelium (RPE) in the development of subretinal neovascularization (SRN) induced by bilateral laser photocoagulation of the retinas in monkeys. RPE function was affected by a unilateral carotid injection of sodium iodate, a selective RPE toxin, before laser photocoagulation. This caused severe RPE damage in the ipsilateral eye, but did not affect the contralateral eye. After laser photocoagulation no SRN was demonstrable clinically or histopathologically in the ipsilateral eye; in contrast, active SRN showing extensive fluorescein leakage was found in the contralateral eye. These results suggest that RPE may play a role in the development of laser-induced SRN.
Laser-induced subretinal neovascularization (SRN) in monkey retinas was investigated by immunohistochemical techniques to identify the presence and location of activated macrophages. Retinal lesions were examined 3, 8 and 14 days after intensive argon laser treatment, and the distribution of interleukin-1 (IL-1)-containing cells in the lesions was determined by the orthogonal reconstruction of serial sections. Macrophages were present in the subretinal space of day 3 and day 8 lesions. These IL-1-containing cells were distributed about the area of rupture of Bruch's membrane and were quite common in lesions taken 3 days following laser treatment. While still apparent, the number was decreased at 8 days, and none were found 14 days after laser treatment. The temporal and spatial distribution of IL-1-staining macrophages paralleled the development of SRN, suggesting a relationship between the presence of activated macrophages and the initiation of neovascularization in this model.
Macrophages are usually present in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR). Information on the kinetics of macrophages in the eye may be of help in identifying their role in this disease. To determine the half-life of macrophages in the vitreous, peritoneal macrophages were labeled by allowing them to phagocytose 141Cerium (gamma-emitter) labeled microspheres, and were then injected into the vitreous of the same rabbit from which they were obtained. The animals were sacrificed at various times post-injection and the radioactivity remaining in the vitreous was measured. Using this procedure, the half-life was found to be 4.8 days.
The early stages (1 day to 3 weeks) in the development of laser-induced choroidal subretinal neovascularization were studied in the monkey eye. Histopathology revealed that the intense laser beam disrupted the choroid/Bruch's membrane/retinal pigment epithelium (RPE) complex and initiated a repair process. Although all lesions received the same energy density, the initial choroidal wound varied among the lesions: in some, the necrotic choroid was surrounded by hemorrhagic retinal detachment with RPE denudation; in others, the necrotic choroid was surrounded only by minimal damage to the RPE monolayer. Formation of the choroidal wound was followed by an inflammatory response. Later, newly formed choroidal tissue filled the wound and continued to proliferate towards the subretinal space. RPE cells from the edges of the wound proliferated over the newly formed subretinal tissue and closed the wound. In lesions with a large area of damaged RPE, coverage of the wound was slow; fluid accumulated in the subretinal space, and the lesions demonstrated pooling of fluorescein on angiography (leaky lesions). In lesions with minimal damage to RPE monolayer, closure of the wound was rapid, and the proliferating choroidal tissue did not reach the subretinal space. There was no subretinal fluid accumulation and no pooling of fluorescein on angiography (nonleaky lesions). Our results indicate that both the amount of damage of the choroid/Bruch's membrane/RPE complex and the ability of RPE cells around the damaged area to proliferate and restore the continuity of the RPE layer determine the evolution of newly formed choroidal fibrovascular tissue into a subretinal membrane with or without pooling.
Injection of activated macrophages into the posterior vitreous of the rabbit induced vigorous fibrovascular proliferation over the optic disk and medullary rays, as demonstrated by 3H-thymidine autoradiography. One week after injection, endothelial cells and pericytes of the capillaries near the inner surface of the optic disk and rays were labeled; fibroblast-like cells, which were also labeled, migrated and formed vitreous strands. By the second week after injection, the fibrovascular tissue proliferated most actively, and traction medullary ray detachment and peripapillary retinal fold formation were observed. The cellular proliferation was accompanied by inflammatory cell infiltration. Glial cells within the optic disk, as well as retinal pigment epithelial cells beneath the detached retina, were labeled by 3H-thymidine. These results demonstrate that the fibrovascular proliferation originates from the vessel complex of the optic disk and medullary rays in this experimental model of retinal detachment.
Macrophages are fully differentiated cells that do not synthesize an extracellular matrix and do not contract; they do, however, produce substances that modify the behavior and functions of other cells, particularly those involved in the inflammatory and immune responses. Since macrophages are a ubiquitous component of periretinal membranes, we sought to determine whether they modulate proliferation and/or migration of retinal pigment epithelial (RPE) cells, functions that may be essential for the development of proliferative vitreoretinopathy (PVR). Using an in vitro assay, we found that macrophage supernatant contains factors that stimulate proliferation and migration of cultured human RPE cells. Since interleukin-1 (IL-1) is a product of activated macrophages that modulates a number of cellular functions, we also examined its effect on RPE proliferation and migration. We found that IL-1 increased migration but did not affect proliferation, and thus could not duplicate the effect of macrophage supernatant. Injection of activated macrophages into the vitreous of rabbits which had a retinal hole stimulated RPE cell proliferation in the area of the retinal hole, where the RPE cells were exposed. These findings suggest the ability of macrophages to modulate functions of RPE cells that are thought to be critical for the development of PVR. Macrophages may thus be an important part of the vitreous environment that favors the development of PVR.
Subretinal neovascularization (SRN) in the rabbit was induced by subretinal injection of vitreous without rupture of Bruch's membrane. Eight of 26 eyes developed SRN. The incidence of SRN rose from 33% to 57% in a period of 4-40 weeks. Because of the absence of any fluorescein angiographic indication of SRN, these occult new vessels were identified by light and transmission electron microscopy. Histological examination showed that these newly formed vessels are composed of continuous capillaries with the morphologic characteristics of choriocapillaris, including diaphragmed fenestrations, basement membranes, and junctional complexes. The new vessels originated from the choriocapillaris and penetrated through Bruch's membrane into the subretinal space, where they were associated with the degenerated sensory retina and proliferating glial and/or RPE cells. This experiment provides a model of SRN without breaks in Bruch's membrane.
Neovascularization and proliferation of the retinal pigment epithelium (RPE) was induced in the rabbit by subretinal injection of vitreous without rupture of Bruch's membrane. New vessels developed between the layer of RPE and photoreceptor outer segments, but were enveloped in proliferating RPE. For this reason they were occult; no fluorescein leakage was visible by angiography. The vessels were identified only by histologic examinations. Endothelial cell budding was the initial stage of vessel development, first seen two weeks after injection. The new vessels grew from the choriocapillaris, penetrated Bruch's membrane, and spread into the subretinal space, despite the absence of subretinal fluid. Fenestrations with diaphragms were found in the endothelial walls during the earliest stages of vessel formation, and were also present in the fully matured vessels. Intermediate junctional complexes were frequently observed among the endothelial cells. During maturation of these plexi, junctions changed from open to putative tight junctions. The mature vessels were ultimately completely enveloped by collagen and RPE cells. Our results show that all new vessels in this animal model have the morphologic characteristics of choriocapillaris. We assume that they leak fluorescein, as does the choriocapillaris, but that the dye has no opportunity to pool in the subretinal space and thus cannot be seen during angiography.
We have investigated the contractile properties of human and bovine retinal pigment epithelial (RPE) cells in culture. In collagen gels, RPE cells sent out processes which were able to retract the gels. In a glycerinated model of contraction, RPE cells contracted and aggregated into clusters in response to the addition of ATP to the media. This contraction was very likely mediated by contractile proteins which are arranged in circumferential microfilament bundles in RPE cells. SDS-PAGE analysis of the RPE cell cytoskeletal elements showed protein bands of 200 kD and 43 kD, probably heavy-chain myosin and actin, respectively; in human RPE, cells bands of 58 kD and 52 kd, representing intermediate filament subunits, were evident; in bovine cells the 58-kD band was observed.