The use of non-linear analysis of the primate ERG to detect retinal dysfunction.
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Biomedical subjects
Publications and source records attributed to S J Ryan.
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A standardised experimental posterior penetrating eye injury in the rhesus monkey with the vitreous-lens admixture resulted in limited fibrous ingrowth from the wound and minimal traction on the peripheral retina. Microscopically inflammation was noted in the iris, ciliary body, and as a perivascular infiltrate of the inner retina. Periretinal membranes did not occur, and cellular proliferation within the vitreous was less marked than observed after an identical wound and simulated vitreous haemorrhage in previously reported studies. The lens may be a less important stimulus to intravitreal fibroblastic proliferation than previously assumed.
This study reports the histological findings in human eyes after severe penetrating trauma. The findings confirm the high incidence of retinal detachment in eyes with severe penetrating injuries. The retina was detached in 32 out of the 34 eyes examined, with 27 having evidence of traction on the retina. These eyes were characterized histologically by intraocular cellular proliferation producing cyclitic, epiretinal, and retroretinal membranes. Intraocular cellular proliferation was discernible or established within 1 week of injury and typically resulted in a cyclitic membrane at about 6 weeks. Epiretinal and retroretinal membranes were found between 1 and 2 weeks after injury in eyes with a detached retina. The results indicate that a damaged lens, the admixture of lens material and vitreous, and the presence of vitreous haemorrhage were all factors promoting intravitreal fibroblastic proliferation. Vitreous surgery may be a rational method of treatment for these severely injured eyes by removing the stimulus and vitreous scaffold for intravitreal fibroblastic proliferation. From this series it would appear that vitrectomy should not be delayed beyond the second week of injury, by which time massive cellular ingrowth may already be under way.
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The principles and guidelines in the management of penetrating ocular injury are detailed. In the absence of definitive clinical trial or an experimental model, the rationale for pars plana vitrectomy has been presented. In addition, our recommendations as to the appropriate role and timing of pars plana vitrectomy are included.
We developed an experimental model for a posterior penetrating eye injury that resulted in traction retinal detachment in 21 rhesus monkey eyes. The standard injury was an incision through the pars plana with vitreous prolapse and incarceration; the wound was then carefully closed with microsurgical techniques. At one to two weeks after injury, detachment of the posterior vitreous occurred and detachment of the retina occurred between seven and 11 weeks. The development of retinal detachment was related to traction on the peripheral retina over the vitreous base; and to the contraction of epiretinal membranes on the peripheral and equatorial retina. Our study supports clinical observations on the importance of blood in the vitreous in the development of vitreous traction and traction retinal detachment after a posterior penetrating injury.
We performed a histologic study to support our clinical observations on the mechanisms responsible for traction retinal detachment after a penetrating injury in the rhesus monkey eye. The monkey eyes (40 eyes; 40 monkeys) were characterized by intraocular fibrosis with the formation of a cyclitic membrane and epiretinal and subretinal membranes. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had its origin mainly from the stroma of the ciliary body and choroid at the wound but probably also from the nonpigmented ciliary epithelium. A fibroblastic response was present within the vitreous as early as four days after injury, and had progressed to form a cyclitic membrane by six weeks. Epiretinal membranes were identified as early as four weeks after injury. They were most prominent over the peripheral retina anterior to the equator. It is likely that they are derived from multiple cellular sources including the fibrous ingrowth from the wound but they were also connected to the surface of the retina by bridges of tissue indicating a glial origin. The subretinal membranes appeared to be derived from both retinal pigment epithelium cells and glial cells.
Visual improvement was achieved in 62% of 100 consecutive patients with ocular trauma treated by pars plana vitrectomy. Anterior segment injuries had a better prognosis than posterior segment injuries, and retinal detachment was a poor prognostic sign. Patients undergoing vitrectomy during the two weeks after injury had a better visual prognosis than those who had delayed vitrectomy. Pars plana vitrectomy has increased the recovery rate in traumatized eyes which previously were deemed inoperable and frequently were enucleated. Most such eyes have intraocular fibrocellular proliferations, resulting in traction retinal detachments, cyclitic membranes, and phthisis, as documented in clinicopathological and experimentally produced specimens of penetrating ocular trauma. Vitrectomy can interrupt this sequence, if performed one to 14 days after injury, by removing the vitreous scaffold onto which proliferation occurs, together with the elements of hemorrhage, damaged lens, vitreous, and foreign material which may incite proliferation. We believe four to ten days after injury to be the optimal time for vitrectomy to avoid the hazards of immediate intervention, while removing damaged tissue before serious sequenlae occur.
Seven patients with chloroquine retinopathy were examined ten years after their therapy with chloroquine or hydroxychloroquine, or both, had been discontinued and an additional five patients with chloroquine retinopathy were similarly examined from two to eight years after their therapy had been discontinued. Visual acuity, visual fields, and ophthalmoscopic examinations were compared to those performed at the time therapy was discontinued. These long-term observations confirmed the previously published observations based on short-term studies that chloroquine retinopathy tends to remain stable after therapy is discontinued, although a few patients in the early stages of retinopathy may show regression and occasionally a patient with a more advanced stage of the disease may show progression.
A technique has been developed which produces an experimental posterior penetrating eye injury that reproducibly results in traction retinal detachment in rabbit eyes. The standard injury is an incision through the pars plana with vitreous prolapse and incarceration; the wound is then carefully closed with microsurgical techniques. It appears that blood in the vitreous is an essential factor in the development of vitreous traction and of traction retinal detachment. The model, which has been successfully transferred to Rhesus monkey eyes, is considered useful for further histological, electromicroscopical, electrophysiological, and ultrasound studies of posterior penetrating injuries of the eye. Our immediate goal is to assess in a controlled experiment whether pars plana vitrectomy can interrupt the sequence of events leading to traction retinal detachment after a posterior penetrating injury.
The histological findings of the wound, the vitreous, and the retina in the rabbit eye with experimental posterior penetrating injury are described. Wound healing had just begun at 3 days after injury and was well established by 9 to 12 days. It involved proliferation of cells from the episclera and from the choroid. The progression to a fibrous ingrowth from the wound occurred only in eyes with blood in the vitreous. The intravitreal fibroblastic proliferation had begen at 6 days after injury and seemed to be derived from the choroid, the nonpigmented ciliary epithelium and, posteriorly, from the optic nervehead. During the development of retinal detachment the configuration of the peripheral and posterior retina, together with the orientation of vitreous strands, suggested the presence of vitreous traction. We postulate that the presence of contractile fibroblasts (myofibroblasts) in the vitreous may provide the mechanism for vitreous traction. The retinal detachments were also characterised by epiretinal and subretinal membranes, but these were not prominent. The end-stage appearance of a soft, shrunken eye with cyclitic membrane formation and retinal detachment resembles the outcome in many human eyes after severe penetrating injuries.
A reproducible model of subretinal neovascularization has been developed, an important first step in the study of disciform macular degeneration. The methodology and clinical description of subretinal neovascularization in the primate have been provided and histopathologic and electron microscopic correlations included. This model provides a most promising and useful mechanism for the evaluation of the many different factors and hypotheses that have been proposed for the genesis of the disciform response. In humans, it probably has more relevance to the traumatically induced disciform process, particularly that after laser therapy, than to the senile degenerative process. The purpose of this investigation is to develop the animal model by which many different theories regarding the pathogenesis of the disciform response can be tested. These initial studies relate to ischemia, hemorrhage, the inflammatory response, and position in relation to the center of the vascular-free zone as factors important in the development and evolution of subretinal neovascularization.
Thirty-four severely injured eyes were operated with pars plana vitrectomy. The nine cases with involvement exclusively of the anterior segment alone were operated with success in all cases. However, the injuries of the posterior segment still reflect significant problems in that only 50 percent obtained successful visual results. This reflects, in great part, the degree of severity of the initial damage. The theoretical rationale for pars plana vitrectomy in penetrating ocular trauma is discussed. Because of the many variables from patient to patient and injury to injury, conflicting clinical impressions as to appropriate management prevail. In the abscence of a definitive clinical trial or suitable experimental model, our guidelines for the role and proper timing of pars plana vitrectomy for penetrating ocular trauma are presented.
A technique has been developed which produces an experimental posterior perforating eye injury, that reproducibly results in traction retinal detachment. The standard injury is an incision through the pars plana with vitreous prolapse and incarceration; the wound is then carefully closed with microsurgical techniques. It appears that blood in the vitreous is an essential factor in the development of vitreous traction and of traction retinal detachment. The model is considered useful for further histological, electron microscopic, electrophysiological, and ultrasonic studies of posterior perforating eye injuries. In a controlled experiment, it will be possible to assess whether pars plana vitrectomy can interrupt the sequence of events leading to traction retinal detachment after posterior perforating injury.
Eight cases of unilateral congenital cataract were operated in the first two years of life. They were treated with contact lenses fitted within the first three weeks postoperatively and with patching of the good eye. None of these eyes achieved better than 3/100 vision. This dense amblyopia would seem based on the marked refractive difference. In addition to the ocular aspects, the psychological aspects of this evaluation would indicate that such surgery and postoperative management is probably not indicated for unilateral congenital cataracts.
A 22-year-old man was seen with the ocular histoplasmosis syndrome. This case demonstrates that spontaneous or "de novo" neovascularization without prior pigmentary changes can occasionally, although rarely, give rise to the disciform macular disease process and the potential for loss of central vision. The lesion initially responded favorably to treatment with heavy argon laser photocoagulation in the parafoveal area, including the papillomacular area, but subsequent areas of neovascularization proved intractable to laser therapy.
Corneal buttons from three patients with congenital central corneal leukoma (Peters' anomaly) were examined by light and electron microscopy. All cases exhibited a central absence of Bowman's membrane and iris synechiae to the periphery of the leukoma. In the first patient, extensive keratolenticular adhesion with retrocorneal fibrous tissue filling the central defect of endothelium and Descemet's membrane implicated late anterior displacement of the normally developed lens as the cause of secondary endothelial degeneration. In the second patient, attenuated endothelium and abnormally composed Descemet's membrane indicated primary dysgenesis of the endothelium. In the third patient, the extensive defect of posterior stroma with anterior stromal disorganization and endothelial metaplasia suggested dysgenesis of both the keratocytic and endothelial mesoderm. Thus, although no unified pathogenic mechanism was consistently applicable, either primary or secondary dysgenesis of the corneal mesoderm must be responsible.