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Biomedical subjects

W H Stern

Publications and source records attributed to W H Stern.

At least 19 recordsLinked to original sources

Sympathetic ophthalmia associated with pars plana vitrectomy without antecedent penetrating trauma.

PURPOSE: To evaluate, describe, and categorize the clinical presentation, clinical course, histopathology, and response to therapy in patients without a history of penetrating ocular trauma who developed sympathetic ophthalmia following pars plana vitrectomy. METHODS: The records of patients without a history of trauma who underwent pars plana vitrectomy and developed sympathetic ophthalmia were retrospectively reviewed. Cases were analyzed with respect to clinical presentation, fluorescein angiographic findings, anatomic and visual outcomes, histopathology, and response to therapy. RESULTS: Eight eyes were identified. The median age at presentation was 55 years, with a range of 14 to 62 years. The time from vitrectomy to diagnosis of sympathetic ophthalmia ranged from 2 months to greater than 2 years, with a median of 7 months. Six of eight patients (75%) presented with anterior chamber reaction. All eight patients presented with a vitreous inflammatory response. The optic nerve was inflamed clinically or angiographically in four of eight cases (50%). Small yellow-white sub-retinal pigment epithelial deposits were present in four of eight cases (50%). Two eyes had lesions characterized as multifocal choroiditis. One eye had larger yellow placoid-like lesions. One eye presented with vitritis but no retinal lesions. Subretinal choroidal neovascularization was noted in the inciting eye of one patient. Vision improved in the sympathizing eye with immunosuppressive therapy in five of eight cases (62.5%). CONCLUSIONS: Sympathetic ophthalmia can be seen following pars plana vitrectomy in patients without penetrating injuries or a history of trauma. Indeed, it may be seen after successful vitrectomy for retinal detachment. Diverse clinical presentations are possible, and persistent or atypical uveitis following vitrectomy should alert the surgeon to the development of sympathetic ophthalmia.

Adolescent↗

Collagen shield heparin delivery for prevention of postoperative fibrin.

We studied collagen shield heparin delivery to the rabbit eye utilizing radiolabeled heparin as well as a fibrin inhibition assay. Radiolabeled heparin studies revealed significant tritium delivery to the cornea, aqueous, and iris, with only trace levels detectable for the lens, vitreous, and sclera. An aqueous fibrin inhibition assay revealed that a single collagen shield soaked in heparin achieved anterior chamber anticoagulant levels that paralleled the time course of the radiolabeled heparin delivery and resulted in fibrin inhibition during the 6-hour study period. Subconjunctival heparin injection did not alter baseline aqueous anticoagulant activity. No complications related to collagen shield heparin delivery were encountered. These studies suggest that a heparin-hydrated collagen shield may prevent postoperative fibrin formation in eyes at risk for this complication, including eyes undergoing surgery for the complications of proliferative diabetic retinopathy proliferative vitreoretinopathy, and glaucoma filtration surgery.

Animals↗

Pathologic observations made by retinal biopsy.

The authors report four cases in which retinal biopsy findings yielded unexpected or previously unreported diagnoses in patients with inflammatory retinitis. The tissue diagnoses included Wegener's retinal vasculitis in an immunosuppressed patient with a clinical diagnosis of cytomegalovirus retinitis, a novel viral form in the retina of a patient with cytomegalovirus retinitis, a case of acute retinal necrosis due to cytomegalovirus infection in an immunologically normal adult, and a case of ganciclovir-resistant herpes family viral retinitis. These cases illustrate the use of retinal biopsy in obtaining tissue for diagnosis and guiding treatment in selected cases of retinitis.

Acquired Immunodeficiency Syndrome↗

Retinoids and butyrate modulate fibroblast growth and contraction of collagen matrices.

Wound healing in the eye may lead to undesirable sequelae such as proliferative vitreoretinopathy and scarring of glaucoma filtering fistulas. We therefore sought to manipulate in vitro two key wound healing processes--cell proliferation and contraction of extracellular matrices--using vitamin A (VA), retinoic acid (RA), and n-butyrate (BUT). These substances modulate growth and differentiation of normal and neoplastic cells. We examined the effects of these agents on cultured rabbit fibroblast proliferation and contraction of collagen matrices. Dermal fibroblast proliferation was unaffected by VA, stimulated by RA, and inhibited by BUT. Scleral fibroblast proliferation, in contrast, was stimulated by both VA and RA. All three agents mildly inhibited fibroblast contraction of collagen matrices. We conclude that 1) VA, RA, and BUT have differential effects on rabbit fibroblast proliferation; 2) retinoid effects on fibroblast growth vary with the tissue of origin; and 3) VA, RA, and BUT modestly inhibit fibroblast contraction of extracellular matrices. This study suggests that fibroblast-mediated processes in ocular wound healing and cicatricial disease may be differentially modulated by retinoids and BUT.

Analysis of Variance↗

Ocular cicatricial disease. Drug effects in vitro on cell proliferation, contraction, and viability.

Fluoroorotate, tunicamycin, and actinomycin D exhibit optimal effects on cell contractility if cells are exposed to the drug for 72 hr, followed by 24 hr of exposure during the contractility assay. Under these conditions, fluoroorotate and tunicamycin inhibit contractility at concentrations very similar to those required to inhibit proliferation, and at higher concentrations affect cell viability. In contrast, the concentrations at which actinomycin D inhibits cell contractility and viability are very similar, and the concentration at which it inhibits cell proliferation is much lower. These results suggest that fluoroorotate and tunicamycin inhibit cell contractility by inhibiting membrane protein glycosylation. Actinomycin D, which inhibits RNA synthesis, appears to block cell contractility only by blocking cell viability, and its most potent effect inhibits only cell proliferation. Daunomycin exhibits very similar effects on cell contractility if cells are exposed to drug for 48 or 72 hr prior to the assessment of contractility, and its effects are not appreciably increased by the further inclusion of the drug for 24 hr during the contractility assay. Daunomycin also has appreciable effects on contractility if cells are exposed to the drug only for the 24 hr of the contractility assay. Similar to actinomycin D, daunomycin inhibits cell contractility and viability at similar concentrations, and inhibits cell proliferation at much lower concentrations. Moreover, daunomycin can appreciably inhibit cell viability in 24 hr of exposure. Therefore, daunomycin appears only to block cell contractility by blocking cell viability, and its most potent effect inhibits only cell proliferation.

Animals↗

The surgical management of giant retinal tears with the cannulated extrusion needle.

In 18 eyes of 17 patients, we treated retinal detachment caused by a giant retinal tear by unfolding and repositioning the retina with a cannulated extrusion needle. After pars plana vitrectomy, a fluid-gas exchange was performed with the patient in the supine position. Using the cannulated extrusion needle to drain subretinal fluid posterior to the giant retinal tear, the retinal flap was manipulated into the correct anatomic position. With this technique, 18 of 18 eyes with retinal detachment caused by a giant retinal tear were successfully reattached intraoperatively. Although eight of these eyes subsequently redetached and required additional surgical procedures, 16 of 18 eyes remain attached with a mean follow-up of 11 months.

Adult↗

Postoperative mycobacterial endophthalmitis.

We treated two sporadic cases of postoperative endophthalmitis caused by rapidly growing (Runyon's group IV) mycobacteria. Both involved intraocular lenses, one a secondary implant after intracapsular cataract extraction (Mycobacterium chelonae subspecies abscessus) and the other a primary posterior chamber lens implantation after extracapsular cataract extraction (pigment-producing member group IV). Signs of inflammation were judged severe enough to warrant diagnostic and therapeutic intervention during the fourth postoperative week in both cases. In both eyes the organism seemed to be eradicated by intravitreal amikacin in combination with vitrectomy, as well as topical, subconjunctival, and, in one case, systemic antibiotic therapy.

Aged↗

Collagen shield enhancement of topical dexamethasone penetration.

Collagen corneal shields were investigated as a vehicle for enhancing the ocular penetration of topical 0.1% dexamethasone alcohol in rabbit eyes. Four protocols were compared: a single dexamethasone drop, hourly drops, a 24-hour collagen shield presoaked in 0.1% dexamethasone, and a presoaked collagen shield followed by hourly drops. Dexamethasone concentrations in the cornea, aqueous, iris, and vitreous were measured by radioassay at six time intervals, and cumulative drug delivery over 6 hours was calculated for each tissue. Treatment with a presoaked collagen shield plus hourly drops resulted in peak and cumulative drug delivery to the cornea, aqueous, iris, and vitreous that was twofold to fourfold higher than delivery achieved with hourly drops alone. A presoaked shield by itself yielded equivalent or superior peak and cumulative drug delivery compared with a regimen of hourly drops. Collagen shields significantly enhance topical dexamethasone penetration and may be useful for maximizing the intraocular delivery of dexamethasone and for decreasing the required frequency of topical dexamethasone administration.

Animals↗

Classification of proliferative vitreoretinopathy used in the silicone study. The Silicone Study Group.

The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas with silicone oil for the surgical treatment of proliferative vitreoretinopathy (PVR). As part of the study, a topographic classification of PVR has been developed that is based on the characteristic patterns of retinal distortion produced by the contraction of proliferative membranes on the retina or within the vitreous base. This classification is used to document the extent and anatomic distribution of PVR present preoperatively and to help standardize the surgical treatment. Experience has shown that this classification facilitates the identification of these membranes and their systematic dissection, and the authors therefore suggest that it be used to augment the Retina Society classification of PVR.

Humans↗

Heparin prophylaxis for intraocular fibrin.

The authors have evaluated the use of heparin as a method to prevent postoperative intraocular fibrin clot formation in the rabbit after vitrectomy and cyclocryotherapy. In addition, they have studied the effect of a heparin infusion on intraocular bleeding after sectioning of retinal vessels. Heparin was administered by several different routes. The extent of the postoperative fibrin clot, as well as the number of days until its clearing, were recorded. A single anterior chamber injection, heparin supplementation of the infusion solution, or a single intravenous (IV) injection, all resulted in a statistically significant reduction of postoperative intraocular fibrin. Once daily subcutaneous injections alone did not produce a reduction in postoperative fibrin. No ocular bleeding complications developed postoperatively. A constant heparin intraocular infusion of 10 IU/cc did not change the bleeding time after sectioning of a retinal vessel.

Animals↗

Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye.

The authors have examined the fate of intravitreally injected liposomes in the aphakic, vitrectomized eye of the rabbit. Liposomes labelled with 125[I]-p-hydroxybenzimidylphosphatidylethanolamine were eliminated rapidly from the intraocular fluid. Nonetheless, a significant fraction of these liposomes were found to bind to various ocular tissues including the retina, iris, sclera, and cornea. Ultrastructural studies with gold colloid-loaded liposomes revealed that retinal bound liposomes were attached to the inner limiting lamina but did not penetrate to the internal cells of the retina. Epiretinal cells bound and internalized gold colloid-loaded liposomes suggesting that these cells may be very sensitive to liposome mediated drug delivery.

Animals↗

Antiproliferative and anticontractile effects of liposome encapsulated fluoroorotate.

Incorporation of fluoroorotate into liposomes increases its growth inhibitory potency for rabbit dermal fibroblasts 30-fold. The optimal lipid composition of the liposomes is dipalmitoylphosphatidylglycerol:cholesterol (67:33). Liposomes prepared by reverse phase evaporation without extrusion are the optimal liposomes for delivery. Fluoroorotate, like other RNA directed fluoropyrimidines, inhibits the contractility of rabbit dermal fibroblasts. The effect is greatest when the cells are exposed to the drug for the 48-72 hr immediately prior to measurement of cell contractility. Encapsulation of fluoroorotate increases its anticontractile potency 10-fold. The anticontractile effects of both free and encapsulated fluoroorotate on the cells last at least 12 days. Leakage studies suggest that the loss of drug from the liposomes under storage conditions will be quite low. Leakage studies also confirm that serum will accelerate the loss of drug from the liposomes and that sonicated liposomes leak much more rapidly than larger liposomes. However, the large difference between egg phosphatidylglycerol and dipalmitoylphosphatidylglycerol liposomes for drug delivery is not explained by leakage studies. These results suggest that encapsulated fluoroorotate may be a useful adjunct to surgery for treatment of proliferative vitreoretinopathy.

Animals↗