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Biomedical subjects

K R Olsen

Publications and source records attributed to K R Olsen.

At least 19 recordsLinked to original sources

Measurement of cellular proliferation within the vitreous during experimental proliferative vitreoretinopathy.

Cellular proliferation is an important component in the pathogenesis of complex retinal detachments caused by proliferative vitreoretinopathy (PVR). We used flow cytometry to measure the proliferation of cells recovered from the vitreous cavity in an experimental model of tractional retinal detachment induced by homologous fibroblast injection. Two distinct populations of cells were detected. One population comprised smaller, dense cells representing mostly leukocytes. A second population of larger cells contained not only the injected fibroblasts but also high concentrations of host-derived cells with significant proliferative activity, whose number increased for 3 days following injection. Flow cytometry was useful for analysis of the recovered cells for concentration, morphologic features and proliferation. This technique may be applicable in the identification of patients at high risk for the development of PVR.

Animals

Tissue plasminogen activator thrombolysis during surgical evacuation of experimental subretinal hemorrhage.

To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes.

Animals

Results and complications in treated retinal breaks.

One hundred sixty-four patients (171 eyes) were treated for retinal breaks and the treatment outcomes were studied. One hundred two eyes were acutely symptomatic, 22 eyes were chronically symptomatic, and 47 eyes were asymptomatic. The reasons for further treatment in 38 of the 171 eyes (22%) included the following: (1) inadequate closure of the original break without detachment in eight eyes (5%), (2) new breaks without detachment in 15 eyes (9%), (3) an operation for retinal detachment caused by the original break in seven eyes (4%), or (4) retinal detachment caused by a new break in eight eyes (5%). Failure rates of treatment among acutely symptomatic, chronically symptomatic, and asymptomatic subgroups were not statistically significant. The risk of treatment failure was higher for aphakic and pseudophakic eyes, and in eyes with peripheral retinal abnormalities in the fellow eye. Among 38 patients with failed treatments, 20 (52%) returned for further examination within one month of initial treatment, whereas eight of the 38 patients with failed treatments (21%) returned six months or more after initial treatment. Peripheral retinal abnormalities were recognized initially in 65 of the 171 fellow eyes (38%) and subsequently developed in nine of the fellow eyes (5%) during the follow-up interval. Further treatment is often necessary after initial treatment of peripheral retinal breaks, emphasizing the need for careful long-term follow-up care.

Acute Disease

Retinal toxicity of human tissue plasminogen activator in vitrectomized rabbit eyes.

The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100 micrograms (all doses were administered in 100 microL of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100 micrograms. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25 micrograms of tissue plasminogen activator. Control eyes received 100 microL of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50 micrograms of tissue plasminogen activator, but all eyes receiving 100 micrograms demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100 micrograms of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25 micrograms of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble.

Animals

Tissue plasminogen activator treatment of experimental subretinal hemorrhage.

Previous investigators have suggested that subretinal blood damages the retina in part because of its solid fibrin meshwork. The role of fibrinolysis in facilitating the clearance of subretinal hemorrhage and preventing degeneration of the overlying retina was studied. Autologous whole blood (0.1 ml) was injected into the subretinal space of 20 rabbits. Twenty-four hours later, the animals were randomized to subretinal treatment with 2.5 micrograms of tissue plasminogen activator or a similar volume of physiologic saline. Mean subretinal hemorrhage thickness 3 days after treatment had decreased to 42% of pretreatment thickness in treated eyes and remained unchanged in control eyes (P less than 0.0005). By 7 days mean clot thickness was 9% in treated eyes and 60% in controls (P = 0.005). Light microscopy revealed severe progressive retinal degeneration in both groups. No histologic evidence of retinal toxicity was found in cat retina after subretinal injection of tissue plasminogen activator (50 micrograms/ml). Although treatment with tissue plasminogen activator accelerated the clearance of subretinal hemorrhage, it failed to prevent secondary retinal degeneration in this rabbit model.

Animals

Studies of tumor-infiltrating lymphocytes from a human choroidal melanoma.

Cell suspensions prepared enzymatically from an ocular choroidal melanoma were cultured in vitro in an effort to generate (1) melanoma tumor cell lines and (2) tumor-infiltrating lymphocytes cytotoxic for ocular melanoma cells. Even though histologic study of the tumor did not show "significant" infiltrating bone marrow-derived cells, lymphocytes were generated readily in cultures to which interleukin-2 was added. Phenotypic analysis of the cultured lymphocytes indicated that T-cells, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were present. Moreover, functional studies of the cultured lymphocytes revealed NK activity, LAK activity, and most importantly, tumor antigen-specific cytotoxic T-cell activity. It was concluded that it is possible to obtain tumor cell lines and tumor-infiltrating lymphocytes from ocular tumors, both of which would be required if cellular immunotherapy of ocular tumors is contemplated. In addition, these results indicate that ocular melanomas can express unique tumor-specific antigens and that the immune system of a patient with such an ocular tumor can perceive these tumor antigens because antigen-specific precursor cytotoxic T-cells were present in the tumor-containing eye at the time of enucleation. The theoretic and therapeutic implications of these findings are discussed.

Adult

Retinal toxicity of recombinant tissue plasminogen activator in the rabbit.

We studied the dose-dependent retinal toxicity of the available commercial preparation of human recombinant tissue plasminogen activator in the normal rabbit eye. Tissue plasminogen activator was injected into the midvitreous cavity of albino rabbits in doses (per 100 microL) of 25, 50, 75, and 100 micrograms. Control eyes received 100 microL of balanced salt solution or tissue plasminogen activator vehicle. No evidence of a retinal toxic reaction was seen in eyes receiving 25 micrograms of tissue plasminogen activator. One of four eyes injected with 50 micrograms showed loss of photoreceptor cells by light microscopy. Severe retinal damage was seen by ophthalmoscopy, electroretinography, and light microscopy in three of four eyes receiving 75 micrograms of tissue plasminogen activator and in all eyes treated with 100 micrograms of tissue plasminogen activator or equivalent vehicle. These results suggest that the commercial recombinant tissue plasminogen activator formulation has a narrow margin of safety in nonvitrectomized eyes and that a component of the vehicle is the toxic factor.

Animals

Subretinal hemorrhage management by pars plana vitrectomy and internal drainage.

We reviewed 14 consecutive cases of subretinal hemorrhage involving the macula, in which surgery to remove the hemorrhage was performed by the authors between February 1984 and January 1989. All patients underwent pars plana vitrectomy and internal subretinal hemorrhage drainage. The causes of subretinal hemorrhages in group 1 were primary rhegmatogenous retinal detachments (three eyes), complications from scleral buckling procedures (three eyes), traumatic retinal detachments (two eyes), and sickle cell retinopathy associated with anticoagulation therapy after a pulmonary embolus (one eye). Group 2 consisted of five eyes with massive subretinal hemorrhage associated with age-related macular degeneration. In group 1, recurrent postoperative retinal detachment occurred in five eyes but reattachment was achieved in eight of the nine eyes, and final visual acuities were 20/400 or better in those eight eyes. In group 2, marked subretinal fibrosis occurred in two eyes. Although three eyes had improved visual acuities, final visual acuities were 5/200 or worse in all five eyes.

Drainage

The site of operating microscope light-induced injury on the human retina.

We determined the site of the focal illumination from the Zeiss OPMI-6 operating microscope on the retina of the phakic and aphakic human cadaver eye by directly observing the illuminating element image on the posterior scleral surface of the globe. With the eye straight ahead and the operating microscope level, the focal oval area of retinal illumination was located superior to the foveola in both the phakic and aphakic eye. Tilting the operating microscope 10 degrees toward the surgeon displaced the entire illuminating element image 0.50 mm below the foveola in the phakic eye and 0.25 mm below the foveola in the aphakic eye. Rotating the eye inferiorly 10 degrees displaced the entire illuminating element image 1.0 mm below the foveola in the phakic eye and 1.25 mm below the foveola in the aphakic eye. Centering the field of view superiorly (viewing the superior limbus) paradoxically displaced the illuminating element image inferiorly, resulting in central foveal illumination. Foveal light exposure was avoided in most eye positions by tilting the microscope at least 10 degrees toward the surgeon.

Aphakia

Biodegradable mechanical retinal fixation. A pilot study.

Mechanical retinal fixation is a useful tool in the armamentarium of vitreoretinal surgeons. Unfortunately, the use of metallic retinal tacks on a permanent basic mandates a retained intraocular foreign body that poses some potential for long-range toxic effects. Herein, we report the results of our initial experience with a temporary, biodegradable mechanical retinal fixation device ("biopin") in rabbits. When compared with metallic tacks, the biopins appeared to be well tolerated intraocularly, with minimal damage detectable at the light microscopic level. Disinsertion of the biopins occurred in 46% of the eyes within two weeks and in all eyes by four weeks. Initial signs of degradation of the biopins were observed at six weeks (median) in the ensectomized/vitrectomized eyes and at 12 weeks (median) in the nonvitrectomized eyes. Differences were found in the occurrence of retinal detachment between animals that underwent lensectomy/vitrectomy with insertion of two metallic tacks and animals that underwent insertion of one biopin without vitrectomy. The biopin has a potential as a vehicle for sustained release of pharmacologic agents to inhibit directly the development of vitreoretinal proliferation, thereby retarding or preventing subsequent retinal traction and detachment.

Animals

Intravitreal tissue plasminogen activator treatment of experimental vitreous hemorrhage.

Intraocular recombinant DNA human tissue-type plasminogen activator (tPA) can promote rapid resolution of intracular fibrin clots and hyphema. The efficacy of intravitreal tPA in promoting the short-term clearance of vitreous hemorrhage was investigated. Five treatment groups with experimentally induced vitreous hemorrhage were studied. The extent of the vitreous hemorrhage was graded based on the visibility of retinal details in each quadrant. Two weeks following intravitreal tPA injection (50,000 IU), the nonvitrectomized group and gas vitrectomy groups, each of which received a single tPA injection, showed a statistically significant reduction of the vitreous hemorrhage, although this was thought to represent only a modest clinical effect. Tractional retinal detachments were noted to develop more frequently in tPA-treated eyes as compared with controls.

Animals

MR technique for localization and verification procedures in episcleral brachytherapy.

Spatial definition of an intraocular tumor and subsequent determination of the actual position of an implanted eye plaque are essential for adequate ocular brachytherapy treatment planning. However, a method for verification of the plaque placement which would provide required 3-dimensional information is not available at present. In addition, tumor localization procedures, including ultrasonography and CT techniques, cannot always offer the precision needed for 3-dimensional definition of an intraocular target. This communication describes a magnetic resonance imaging technique specifically developed for both localization and verification procedures. A 1.5 Tesla magnetic resonance scanner, spin-echo pulse sequence (echo time 30 msec, repetition time 700 msec), and commercially available surface coil were used to obtain a series of transverse, coronal, and sagittal images of a slice thickness of 3 mm. Usually, eight scans in each of the three planes were needed for adequate coverage of the orbit. The required patient set-up and data acquisition time did not exceed 40 minutes. With a data matrix size of 256 X 256 pixels and 13 cm field of view, localization and verification were accomplished with a precision of 0.5 mm. Our results suggest that the magnetic resonance imaging technique permits precise integration of diagnostic and therapeutic procedures, and in addition provides adequate data for accurate treatment planning. We conclude that magnetic resonance imaging is the preferred diagnostic technique for episcleral brachytherapy.

Brachytherapy

Predictors of scleral rupture and the role of vitrectomy in severe blunt ocular trauma.

We reviewed retrospectively 40 eyes that had received blunt trauma and had been explored for scleral rupture. Twenty-nine eyes had scleral rupture. Of these 29, ten had ruptures seen preoperatively. Nineteen had occult ruptures. The preoperative findings predictive of scleral rupture were a visual acuity of light perception or no light perception, an intraocular pressure of less than 10 mm Hg, hyphema, and chemosis. Of the 29 ruptures, 27 involved the superior hemisphere and 25 involved the anterior hemisphere of the globe. Ten of 29 eyes (34%) with scleral rupture and eight of 11 eyes (73%) without rupture achieved a final visual acuity of 5/200 or better over an average follow-up period of 6.7 months. Factors prognostic of ambulatory vision for eyes with ruptured and intact globes included an initial visual acuity of 5/200 or better, absence of scleral rupture, and a rupture length of less than 11 mm in eyes with ruptures. The vitrectomized eyes also had a better result, suggesting that early pars plana vitrectomy is of benefit in selected rupture cases.

Eye Injuries

Hypodermic stainless steel tacks and companion inserter designed for peripheral fixation of retina.

Mechanical fixation of the torn or cut edge of retina with 30-gauge hypodermic stainless steel tacks has been performed in 15 patients at the Bascom Palmer Eye Institute, Miami, and Miami Veterans Administration Medical Center with six to 18 months of follow-up. The companion tack inserter allows the surgeon to select an angle for the shaft of the tack in relation to the inserter to allow the tack to be driven perpendicularly into sclera even when the insertion is anterior to the equator. If residual detachment remains following fluid-gas exchange after preliminary placement of the retinal tacks, a given tack may be removed and reinserted to facilitate complete retinal reattachment. This utilitarian feature allows the surgeon to eliminate residual anteroposterior traction following complete membrane peeling by extending relaxing retinotomies and tacking the posterior cut edge of the retina securely between the ora serrata and the equator.

Adult

Fluorouracil therapy of intraocular Greene melanoma in the rabbit.

We evaluated the efficacy of intraocular and periocular fluorouracil treatment in an experimental iris tumor of the rabbit (Greene amelanotic melanoma). Four consecutive intravitreal injections of 1 mg of fluorouracil given twice weekly completely suppressed tumor growth in all treated eyes for six weeks if treatment was initiated 24 hours after tumor implantation. In contrast, all control eyes implanted with an equal number of Greene melanoma cells but treated with intravitreal saline developed massive tumor invasion of the iris within two weeks. Additional subconjunctival therapy following intravitreal therapy for two weeks was only slightly more effective than intravitreal therapy alone. If therapy was delayed for one week, the iris tumors became macroscopically visible and subsequent treatment with intravitreal and subconjunctival fluorouracil was of limited value in suppressing growth.

Animals