Ocular toxicity of intravitreal vidarabine solubilized in dimethyl sulfoxide.

Intravitreal injections of the antiviral drug vidarabine in doses of 10, 50, 100, and 200 micrograms dissolved in 100% dimethyl sulfoxide (DMSO) were administered to the eyes of 12 Dutch and New Zealand pigmented rabbits to determine ocular toxicity. The eyes were examined one week, one month, and two months after inoculation with slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and histopathologic examination with light and electron microscopy. No permanent damage to ocular tissue was found at a vidarabine concentration of 100 micrograms/mL. The antiviral activity and the toxicity of the vidarabine dissolved in DMSO were tested in vitro on herpes simplex virus type 1-infected rabbit corneal fibroblast monolayers. Vidarabine dissolved in DMSO was found to possess in vitro antiviral activity against herpes simplex virus type 1. Our results suggest that the intravitreal administration of vidarabine dissolved in DMSO may be a safe and effective means of drug therapy.

The ocular effects of gases when injected into the anterior chamber of rabbit eyes.

We studied the toxic effects of sulfur hexafluoride and perfluoropropane in comparison with air, balanced salt solution, hyaluronate sodium, and aqueous humor in a rabbit model. Sixty normal pigmented rabbits were studied during a period of 4 weeks. The variables studied were slit-lamp biomicroscopic examination of the anterior segment, intraocular pressure as measured by pneumotonometry, corneal thickness and endothelial cell count as measured by specular microscopy, lens opacity by Scheimpflug photography, and light and transmission electron microscopy. All three gases were more toxic to the cornea and lens than were balanced salt solution, hyaluronate, and aqueous humor. However, 15% perfluoropropane and 50% sulfur hexafluoride were no more toxic to the eye than air was. Therefore, this study suggests that nonexpansile mixtures of perfluoropropane and sulfur hexafluoride may be beneficial and relatively safe in re-forming persistently flat anterior chambers in situations where the use of air is being considered.

Glaucoma-inducing mechanisms in eyes with retinoblastoma.

A total of 149 eyes with retinoblastomas were examined histopathologically to determine the types and frequencies of mechanisms inducing glaucoma. The most common mechanism was iris neovascularization with secondary peripheral anterior synechiae formation. In such cases, the tumor was almost always located at the posterior pole with involvement of central retinal vessels and with growth of a highly vascularized tumor mass into the vitreous. The second most common mechanism was massive exudative retinal detachment causing pupillary block and angle closure. In such cases, tumor growth was present within and under the retina. The third most common mechanism was a combination of the aforementioned mechanisms. Uveitis and/or necrotic tumor tissue in the anterior chamber as the sole mechanism inducing glaucoma was infrequently seen.

Moxalactam retinal toxicity.

Moxalactam disodium is a new third-generation semisynthetic, broad-spectrum, cephalosporin-like antibiotic for parenteral administration. Topical, subconjunctival, and intravenous administration provide poor concentration in the vitreous. To determine its toxicity in intravitreal administration, we injected comparative doses directly into the vitreous cavity of 21 rabbits. With doses of 1.25 mg or less there was no toxic damage to the retina. With a dose of 2.5 mg, early degeneration of photoreceptors was seen after three months. With higher doses (5 and 10 mg) there were major histopathologic and electroretinographic changes. These results suggest the feasibility of employing moxalactam in the treatment of acute, severe, fulminant bacterial endophthalmitis.

Ocular manifestations of focal dermal hypoplasia syndrome.

Although 40 percent of patients with the focal dermal hypoplasia syndrome have ocular abnormalities, to our knowledge, only one case of this condition has been previously described in the ophthalmic literature. Two additional cases are presented, and the systemic and ocular findings are reviewed.

A report of iris neovascularization: an indication for carotid endarterectomy.

The combined use of goniophotocoagulation and carotid endarterectomy may be an important mode of treatment of iris neovascularization caused by carotid insufficiency. Carotid operation alone in cases of iris neovascularization has not been successful in controlling the concomitant or ensuing neovascular glaucoma. When more severe symptoms of carotid occlusion occur, such as transient ischemic attacks or visual loss, it may be too late to reverse the damage of neovascular glaucoma. In this case report, early detection of the iris neovascularization, goniophotocoagulation, and carotid operation were successful in the prevention of neovascular glaucoma and blindness.

Essential thrombocythemia and central retinal vein occlusion with neovascular glaucoma.

PURPOSE: We report a case of unilateral central retinal vein occlusion resulting from essential thrombocythemia, a rare myeloproliferative disorder with abnormally increased platelet count. METHODS: A 59-year-old man had central retinal vein occlusion in the left eye as the initial sign of essential thrombocythemia. He later developed neovascular glaucoma and optic disk neovascularization. RESULTS: Laser panretinal photocoagulation, goniophotocoagulation, glaucoma medications, and control of the platelet count were effective treatment. CONCLUSIONS: Early thrombocythemia is associated with systemic and ocular thrombotic and embolic complications. Early diagnosis, recognition of ocular complications, and appropriate treatment were crucial in controlling central retinal vein occlusion and ocular neovascularization associated with essential thrombocythemia.

Foveal hypoplasia and bilateral 360-degree peripheral retinal rosettes.

A 24-year-old woman had bilateral pendular nystagmus, foveal hypoplasia, 360-degree peripheral retinal rosettes, and hypoplastic ora serrata of nongenetic origin. Kinetic perimetry revealed a generalized constriction of the field. Flicker perimetry revealed general depression of the critical flicker frequencies in the entire field. A slight increase of the threshold for light sensitivity after dark adaptation was noted from 10 to 30 degrees. Haidinger brush phenomenon was abnormal. Color vision was normal. The electroretinogram revealed mild abnormalities in the photopic flicker response. The visual-evoked response, recorded by local macular stimulation, was abnormal. The relationship of foveal hypoplasia to peripheral retinal rosettes in this case may have been caused by an intercurrent infection during the late stages of embryogenesis.

Intraorbital air simulating an intraocular foreign body.

PURPOSE: To present an ultrasonographic finding that simulated an intraocular foreign body after repair of a ruptured globe. METHOD: Case report. An ultrasonogram of a post-trauma eye was correlated with a computed tomographic scan. RESULTS: B-scan ultrasonography was performed on an eye after repair of a corneoscleral laceration. The ultrasonogram showed a highly reflective echo source suggestive of a foreign body; however, an orbital computed tomographic scan demonstrated that the lesion was intraorbital air. CONCLUSION: Although a highly reflective echo source in the presence of a ruptured globe may suggest a foreign body, the presence of orbital air should also be considered when interpreting ultrasonograms used in the preoperative and postoperative management of globe trauma.

Transscleral iontophoresis of foscarnet.

Current local treatments of cytomegalovirus retinopathy may result in serious intraocular complications. Using an animal model, we investigated transscleral iontophoresis as a technique for delivery of foscarnet to the vitreous. Using a probe tip surface area of 0.19 mm2, a current of 1 mA, and a duration of ten minutes, transscleral iontophoresis of 0.5 ml of a 24-mg/ml foscarnet solution was administered to 72 normal rabbits. Vitreous aspiration was performed at 12 intervals (15 minutes, 30 minutes, and one, two, four, eight, 16, 24, 32, 40, 48, and 60 hours) after iontophoresis, and samples were analyzed by high-performance liquid chromatography to determine the vitreous pharmacokinetics of foscarnet. A peak foscarnet concentration of 200 +/- 31 microM (mean +/- standard deviation) was attained four hours after iontophoresis and was well below the concentration reported to cause retinal toxicity. Therapeutic levels were maintained until 60 hours after iontophoresis. The elimination half-life was approximately 24 hours. No toxic effects to anterior chamber structures were observed by biomicroscopy. Transscleral iontophoresis of foscarnet may provide an effective and safe technique for local treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome.

Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia.

From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia.

Ocular iontophoretic supplementation of intravenous foscarnet therapy.

PURPOSE: Reactivation of cytomegalovirus retinopathy during intravenous antiviral therapy is usually treated with higher doses of drug. We sought to determine whether ocular iontophoresis increases the intravitreal foscarnet concentration attained by intravenous injection. METHODS: We injected foscarnet (120 mg/kg or 180 mg/kg) intravenously into 24 rabbits and determined the time of maximal concentrations in serum and vitreous humor. We injected the same doses into 24 additional rabbits and administered ocular foscarnet iontophoresis one hour later. Vitreous humor concentrations were assayed at one, four, eight, 24, 60, and 120 hours after iontophoresis and compared with those from injection alone. RESULTS: Maximum serum and vitreous humor concentrations were achieved one hour after each intravenous dose. Maximum vitreous humor concentrations were achieved four hours after 120 mg/kg intravenous doses plus iontophoresis and eight hours after 180-mg/kg intravenous doses plus iontophoresis. Vitreous humor levels were significantly higher in eyes receiving intravenous foscarnet (120 mg/kg, P < .0001; 180 mg/kg, P < .0001) plus ocular Foscarnet iontophoresis than in those receiving intravenous foscarnet alone. Vitreous humor foscarnet levels in eyes receiving 120 mg/kg intravenously did not differ significantly from those in the group receiving 180 mg/kg intravenously (P < .1). The intravenous dose did not significantly affect vitreous humor levels after iontophoresis (P < .1). Vitreous concentrations fell below therapeutic levels (25 microM) in all eyes 60 hours after intravenous foscarnet and ocular foscarnet iontophoresis. CONCLUSIONS: Ocular iontophoresis significantly increased intravitreous foscarnet concentrations above those attained by intravenous injection alone and may be an effective alternative to increasing the intravenous drug dose in patients with reactivated cytomegalovirus retinopathy.

Localisation of macrophage lysosomal enzyme in experimental toxoplasma retinitis.

Rabbit retinal tissue experimentally infected with Toxoplasma gondii was processed for the lysosomal enzyme aryl sulphatase. Abundant lysosomal activity was found in lysosomal bodies of the infected macrophages. There appeared to be a lack of fusion of the lysosomal bodies with the phagosomes containing the organisms. Examination of the majority of macrophage vacuoles containing trophozoites failed to show consistently lead sulphide deposition for aryl sulphatase activity. By light microscopy 83% of 115 macrophage vacuoles containing the trophozoites of T. gondii showed an absence of lysosomal enzyme activity; 7% of the vacuole containing the trophozoites were found to contain lysosomal enzyme activity. In the remaining 10% of the vacuoles containing the trophozoites of T. gondii the presence or absence of lysosomal enzyme activity could not be determined with certainty. The frequent absence of lysosomal enzyme activity within the phagosomes containing T. gondii organisms may be related to the parasite's ability to multiply and encyst in an intracellular locus. The abundant lysosomal enzyme activity in the lysosomal bodies within the cytoplasm of the infected macrophages may contribute to the cellular destruction of surrounding tissues when infected macrophages burst open owing to proliferation of the trophozoites.

Pars plana incisions of four patients: histopathology and electron microscopy.

The pathology of pars plana incisions of four patients is described: three with light microscopy and one with light and electron microscopy. Two eyes were removed because of choroidal melanoma, immediately and 8 days after vitrectomy and transvitreous retinal biopsy. Considerable disruption of tissues surrounding the pars plana incisions was observed. Vitreous was incarcerated in the wounds, which healed with granulation tissue. One eye was examined 4 months after vitrectomy for diabetic retinopathy and a failed pars plana filtering operation. It contained fibrovascular ingrowth from all the incisions, infiltrating the vitreous base with granulation tissue and causing vitreous haemorrhage and retinal detachment. One eye was removed 1 year after vitrectomy for anterior hyaloidal fibrovascular proliferation and early phthisis. The wound had fibrous ingrowth histologically and evidence of active fibroplasia.

Experimental Toxoplasma retinitis: a light and electron microscopical study.

In a light and electron microscopical study of the morphological lesions of acute experimental Toxoplasma retinitis in the rabbit, produced by intravitreal inoculation with RH strain T gondii, all layers of the retina were found to be infected with the parasite. The Bruch membrane appeared to be a relatively impermeable barrier to invasion by the parasite. The underlying choroid showed an inflammatory cellular infiltrate but was free of organisms. Evidence of lateral spread of infection between the layers of the retinal tissue was observed. Examples of glial cell infection were also seen. Trophozoities may enter the brain by spreading along contiguous glial cell elements of the optic nerve; retinal tissue destruction occurs by direct invasion of cells by trophozoites. In other areas, tissue destruction by inflammatory cells occurred in the absence of organisms and may indicate an immunologically induced process of tissue destruction.

Pharmacodynamics of subconjunctival gentamicin after experimental cataract operations and traumatic lacerations.

We addressed the concern whether retinal toxicity could occur with subconjunctival gentamicin injections after cataract operations or traumatic corneoscleral lacerations. The lacerations were created along the superior limbus of rabbit eyes and the lenses removed. We sutured the right eyes to mimic a cataract operation and the left eyes remained unsutured to mimic a traumatic corneoscleral laceration. Vitreous humor samples were obtained at 1, 2, 4, 8 and 12 hours after the subconjunctival injection, but in no case did vitreal concentration approach retinotoxic levels (> 133 micrograms/ml).

Determination of ocular toxicity in multiple applications of foscarnet iontophoresis.

This is the first study of multiple applications of drug iontophoresis in the eye. We repeated ocular foscarnet iontophoresis in 10 eyes of 10 rabbits every third day at the same paralimbal site for a total of seven applications over a period of 21 days to determine the efficacy and toxicity of multiple applications of ocular foscarnet iontophoresis. Mean vitreous human foscarnet concentration of 189 +/- 50.6 microM (SD) was achieved four hours after the seventh consecutive iontophoretic application over a period of twenty-one days. These levels were within the therapeutic range (25-800 microM) for the treatment of CMV retinitis and comparable to the intravitreal foscarnet concentrations achieved in eyes treated with a only a single application of ocular iontophoresis. Electroretinography (ERG) and Slit-lamp biomicroscopy responses revealed no evidence of ocular toxicity. Indirect ophthalmoscopy of the retinas and gross examinations of the calottes revealed a single, small burn in the retina and choroid corresponding to the application site of the iontophoresis probe similar to the lesion resulting from a single application of iontophoresis. Light and electron microscopy revealed local tissue injury and fibrosis at the iontophoresis site, but adjacent areas were unaffected.

High dose intramuscular methylprednisolone in experimental Staphylococcus aureus endophthalmitis.

We attempted to determine whether treatment using intramuscular methylprednisolone plus intravitreal vancomycin decreased ocular inflammation and preserved retinal function better in experimental Staphylococcus aureus (S. aureus) endophthalmitis than treatment with intravitreal vancomycin alone. Sixteen rabbits received intravitreal inoculations in both eyes with S. aureus and the rabbits were divided into two groups (group I and group II) of eight rabbits each. Group I rabbits were treated with one injection of intravitreal vancomycin in each eye at either 24, 36, 48 or 72 hours after bacterial inoculation followed by seven consecutive days of high dose intramuscular methylprednisolone (30 mg/kg per day). Group II rabbits were treated with only one intravitreal injection of vancomycin in each eye at equivalent time intervals as in Group I. Clinical evaluations of ocular inflammation were performed by slit-lamp biomicroscopy and indirect ophthalmoscopy. Electroretinography (ERG) was performed eight days after bacterial inoculation to assess retinal function in all eyes. The combination of intramuscular methylprednisolone and intravitreal vancomycin resulted in a degree of ocular inflammation equal to eyes treated with intravitreal vancomycin alone at all treatment intervals. ERG responses were not significantly different in either group. A single intravitreal injection of vancomycin plus daily intramuscular methylprednisolone for seven days were found neither to decrease ocular inflammation nor preserve retinal function better than a single intravitreal injection of vancomycin in our experimental model of S. aureus endophthalmitis.

Ocular toxicity of iontophoretic foscarnet in rabbits.

Transscleral iontophoresis of foscarnet is a noninvasive drug delivery system for the local treatment of cytomegalovirus (CMV) retinopathy. We determined the retinotoxic effects of transscleral iontophoresis of foscarnet. Slit-lamp biomicroscopy revealed no toxic effects for any of the treated eyes. Indirect ophthalmoscopy showed retinal and choroidal burns 1-3 mm in diameter at the site of iontophoresis in both foscarnet-treated eyes and saline-treated control eyes. Light and electron microscopy revealed focal retinal, retinal pigment epithelial, and choroidal necrosis at the site of iontophoresis but no abnormalities elsewhere. Ganzfeld electroretinographic studies revealed no response differences between foscarnet-treated eyes vs. controls.