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Biomedical subjects

R Machemer

Publications and source records attributed to R Machemer.

At least 37 records · Page 2Linked to original sources

Retinal separation, retinotomy, and macular relocation: I. Experimental studies in the rabbit eye.

An animal model in the rabbit eye was utilized to study mobilization and relocation of the fovea as a potentially beneficial surgical approach to age-related macular disease. After lentectomy and vitrectomy, the retina was completely separated from the pigment epithelium by means of infusion into the subretinal space. A 360 degrees peripheral retinotomy was performed. The retina was rotated up to 60 degrees around the optic nerve as axis and reattached. Scanning and transmission electron microscopy revealed the relative intactness of outer segments and pigment epithelium after this procedure, both acutely and 3 days following reattachment.

Animals↗

Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration?

Three cases of age-related maculopathy with severe and recent massive submacular hemorrhage were treated by performing complete vitrectomy. A total retinal detachment was created by infusion of fluid underneath the retina, followed by a peripheral circumferential retinotomy. This allowed access to the subretinal space for removal of blood and membranes and, more importantly, permitted rotation of the retina with relocation of the fovea. Rotations between 30 degrees and 80 degrees were achieved. One patient with 5 months' follow-up had a visual improvement from 1/200 to 20/80 and excyclorotation of images. The other two patients developed proliferative vitreoretinopathy after initially successful rotation. Their retinas were reattached after surgical removal of the membranes and silicone oil tamponade, but visual function remained low. The rationale for this treatment is that relocating the fovea to an area where pigment epithelium is less diseased than in the central area may allow for recovery of some useful vision.

Aged↗

Ocular toxicity of daunomycin: effects of subdivided doses on the rabbit retina after vitreous gas compression.

Daunomycin is a potent antiproliferative agent which has been shown to prevent experimental proliferative vitreoretinopathy. However, toxic effects on the rabbit retina have been reported even for the lowest effective doses. In a previous report we demonstrated that subdivided doses rather than single doses of daunomycin improves the efficacy in prevention of experimental proliferative vitreoretinopathy. To evaluate whether dose subdivision would also have an alleviating effect on drug toxicity, we administered 15 nmol daunomycin in doses of 10 nmol and 5 nmol 4 h apart into the vitreous cavity of rabbit eyes which had previously undergone vitreous gas compression. All contralateral eyes received sham treatment. Simultaneous electroretinographic recordings from both eyes on days 0, 3, 7, and 14 demonstrated a significant b-wave decline in drug-exposed eyes. Morphological studies on these eyes revealed no retinal damage. Our findings suggest that dose subdivision does not eliminate the retinal toxicity of daunomycin.

Animals↗

The effects of intravitreal triamcinolone acetonide on experimental pre-retinal neovascularization.

Corticosteroids, alone or in combination with other drugs, have been shown to inhibit angiogenesis. The purpose of this study was to evaluate the efficacy of triamcinolone acetonide in a new model of preretinal neovascularization. Rabbit eyes were treated with intravitreal triamcinolone acetonide 24 h before partial liquefaction of the posterior vitreous with hyaluronidase and injection of 250,000 homologous tissue-cultured dermal fibroblasts. Triamcinolone acetonide effectively inhibited new vessel growth in treated eyes. Only 14% of the treated eyes developed new blood vessels compared to 100% of sham-injected control eyes (P < 0.001). These results suggest that intravitreal triamcinolone acetonide might be effective in inhibiting new vessel growth in patients with inflammatory retinal neovascularization, such as that associated with sarcoidosis or other uveitic syndromes.

Animals↗

Aclacinomycin A in the treatment of experimental proliferative vitreoretinopathy. Efficacy and toxicity in the rabbit eye.

PURPOSE: Aclacinomycin A is an oligosaccharide anthracycline that, by contrast with daunomycin, lacks carcinogenicity. The authors evaluated the efficacy of aclacinomycin A in prevention of experimental proliferative vitreoretinopathy (PVR) and its toxicity on the rabbit retina. METHODS: Dutch-belted rabbit were used to create a model for traction retinal detachment. Seven to 10 days after vitreous gas compression, 25,000 homologous fibroblasts were injected into the vitreous cavity. Subsequently, the eyes received either sham injections or doses of 6, 30, or 60 nmol of aclacinomycin A, respectively. The fundus findings were documented on days 7, 14, and 28 after the fibroblast injection. The toxicity studies were conducted according to the same protocol as was used for the efficacy evaluation but without the fibroblast injection. Simultaneous electroretinograms were recorded on days 0, 3, 7, and 14 from the right eyes that were injected with 30 or 60 nmol of aclacinomycin A and the left eyes that were sham injected. Morphologic studies were conducted on the eyes enucleated on days 3, 7, and 14 after drug exposure. RESULTS: Intraocular administration of 30 nmol of aclacinomycin A on day 2 after fibroblast injection resulted in a detachment rate of 37.5% (controls, 100%; P < 0.01, by Fisher's exact test). Administration of 60 nmol of aclacinomycin A 3 days after fibroblast injection resulted in a detachment rate of 26.7% (controls, 100%; P < 0.0001). Six nanomoles of aclacinomycin A 3 days after fibroblast injection had no effect. No electroretinogram changes were present in eyes treated with 30 nmol of aclacinomycin A. Such recordings from eyes exposed to 60 nmol of aclacinomycin A demonstrated decreased a- and b-waves on day 3; these completely recovered by day 7. Morphologic studies of these eyes revealed no damage to the retina. CONCLUSIONS: These results suggest that aclacinomycin A should be considered an alternative to daunomycin for treatment of human PVR because, in addition to its lack of carcinogenicity, it shows good efficacy and causes less retinal toxicity.

Aclarubicin↗

Retinal oxygenation and laser treatment in patients with diabetic retinopathy.

The oxygen tension in the preretinal vitreous cavity was measured in human patients undergoing vitreous operations for proliferative diabetic retinopathy. The oxygen tension was significantly higher (P = .004) over areas of retina that had been treated with panretinal photocoagulation than it was over untreated areas in the same retina. This confirmed previous results in animals that showed that panretinal photocoagulation increases the inner retinal oxygen tension. We concluded that panretinal photocoagulation improves the oxygen supply to the inner retina and thereby minimizes the influence of retinal ischemia in diabetic retinopathy.

Blood Pressure↗

The lack of an effect of intraocular steroids on irradiated fibroblasts in experimental proliferative vitreoretinopathy.

Contraction of intraocular membranes is an important event in the development of proliferative vitreoretinopathy (PVR). When sufficient numbers of cells are present in the vitreous cavity, the retina usually detaches as a result of the contractive force generated by these cells. Steroids reduce the occurrence of retinal detachments in rabbit models of PVR by inhibiting the proliferation of injected fibroblasts. In this study, we used non-proliferative, irradiated cells to determine a possible effect of steroids on preretinal membrane contraction in PVR. We found no clinical difference between steroid treated eyes and sham-treated control eyes. Surgical reduction of the contractile tissue and medical therapy to prevent reproliferation are necessary in order to treat PVR effectively.

Animals↗

Pigment epithelial repair.

We studied the repair of large, surgically induced retinal pigment epithelial defects in rabbit eyes for up to 28 days. Ophthalmoscopically, the pigment epithelium surrounding the defect became less pigmented and scattered pale foci appeared. The margin remained distinct for 28 days and the defect was subsequently covered by a variable lacework of pigmentation. Angiographically, the acute defect was hyperfluorescent and leaked heavily, but within 7 days fluorescein leakage had ceased. Histology, transmission and scanning electron microscopy, and autoradiography for the study of cells in division revealed that the pigment epithelium surrounding the defect became pleomorphic after 1 day, began to proliferate within 3 days, and covered the defect within 7 days. Subsequently, many cells became pigmented and some were fibrocyte-like. The cells within the healing defect appeared to have derived from the pigment epithelium. Our findings suggest that similar processes occur in large human defects such as pigment epithelial rips.

Animals↗

Scleral buckling surgery for stage 4B retinopathy of prematurity.

Results of scleral buckling in 15 consecutive eyes of 13 infants with stage 4B retinopathy of prematurity (ROP) were reviewed. Ten of 15 retinas achieved macular reattachment with a single scleral buckling procedure. Four of 15 retinas unable to be attached by scleral buckling were reattached after the addition of a single vitreous operation. One of 15 retinas was unable to be reattached despite both a scleral buckling and a single vitreous procedure. Despite macular attachment in all except one eye, visual results were disappointing. Fix and follow visual acuity was present in 3 eyes, light perception in 11 eyes, and no light perception in 1 eye. Average follow-up was 10 months. Possible causes for poor visual outcomes despite retinal reattachment include retinal abnormalities as a result of detachment and amblyopia.

Female↗

An updated classification of retinal detachment with proliferative vitreoretinopathy.

The Retinal Society classification on proliferative vitreoretinopathy of 1983 has been updated to accommodate major progress in understanding of this disease. There are three grades describing increasing severity of the disease. Posterior and anterior location of the proliferations have been emphasized. A more detailed description of posterior and anterior contractions has been made possible by adding contraction types such as focal, diffuse, subretinal, circumferential contraction, and anterior displacement. The extent of the abnormality has been detailed by using clock hours instead of quadrants.

Eye Diseases↗

Light damage in detached retina.

We injected homologous fibroblasts over the retinal vascular wing in five rabbits to induce a tractional retinal detachment. Eleven days later, a focal area of detachment was exposed to 30 minutes of visible light by an intraocular fiberoptic probe. Histologic damage to the detached retina exposed to light was demonstrated. The outer retina was affected most severely.

Animals↗

Daunorubicin treatment in a refined experimental model of proliferative vitreoretinopathy.

A condition similar to proliferative vitreoretinopathy (PVR) in man can be produced by injecting 25,000 homologous dermal fibroblasts into rabbit eyes following gas compression of the vitreous. Daunorubicin (15 nmol) was effective in preventing retinal detachment in this model when injected simultaneously with the fibroblasts or in two doses (10 nmol followed by 5 nmol 4 h later) on the 3rd day after fibroblast injection. A single dose of 15 nmol on the 3rd day was not effective in preventing retinal detachment. These results suggest that daunorubicin may be clinically useful in preventing PVR when given by injection both at the time of vitrectomy as well as later, when protein exudation and pigment clumps in the vitreous cavity herald the onset of PVR.

Animals↗

Experimental traction retinal detachment in the cat.

We developed a reproducible model of traction retinal detachment (TRD) in the cat eye by creating a serous retinal detachment and then injecting 2.5 x 10(5) kitten dermal fibroblasts into the vitreous cavity at the site of a retinal wound. Serous detachments were produced by exposing an area of retina to focused light after intravenous injection of rose bengal (a photosensitizing dye). TRD developed rapidly within the first 2 weeks after fibroblast injection, accompanied by the formation of vitreoretinal strands and, to a lesser degree, epiretinal and/or subretinal proliferation. Histopathology demonstrated fibroblasts within the vitreous or along the posterior hyaloid face. Focal deposits of fibroblasts were occasionally found on the inner surface of the retina and/or in the subretinal space. Fibroblast proliferation was confirmed by uptake of radiolabeled thymidine. Deposition of collagen was noted at as early as 3 days after fibroblast injection. Neovascularization was not observed. Control eyes that did not receive fibroblasts showed resolution of serous detachment without retinal traction. In all eyes, retinal degeneration and thinning were seen in the area of previous photodynamic treatment. In this model of TRD, anteroposterior traction (due to vitreous strands) predominates, as is observed in experimental posterior penetrating ocular injury induced by intravitreal blood injection, which also results in vitreous strand formation. Our model, however, enables clinical assessment of TRD in the cat without the media opacification produced by vitreous blood.

Animals↗

An experimental model of preretinal neovascularization in the rabbit.

Although progressive retinal neovascularization is a potentially blinding complication of several diseases, there are no good animal models. The authors developed a consistent model of preretinal neovascularization in the rabbit by partially digesting the posterior vitreous with repeated injection and aspiration of 1 IU of hyaluronidase before injection of 250,000 homologous dermal fibroblasts. The evolution of the new preretinal vessels was monitored by indirect ophthalmoscopy, fundus photography, and fluorescein angiography. A grading system was devised using fundus photographs and fluorescein angiograms to describe the progression of new vessel growth and the extent of fluorescein leakage. Ninety-five percent of the eyes had vascular enlargement and hyperemia but no fluorescein leakage by day 1. Fifteen percent of the eyes had clinically evident new preretinal vessels, and 32% had severe fluorescein leakage by day 7. Ninety-five percent of the eyes had definite neovascularization by day 14. Severe fluorescein leakage peaked at day 14 (55% of the eyes) and decreased thereafter. Involution or atrophy of the vessels occurred in all eyes by day 42. This model will be useful for studying the pathogenesis of preretinal neovascularization and evaluating potential treatments for its prevention.

Animals↗

Clinical and histologic effects of extreme intraocular hypothermia.

Rabbit eyes in which vitrectomy was performed underwent three hours of hypothermic perfusion with either 22 C or 2 C lactated Ringer's solution. Clinical, electroretinographic, fluorescein angiographic, histologic, and ultrastructural examinations were performed. No changes were noted in eyes cooled with 22 C fluid. Reversible lens opacities, equivocal electroretinographic changes, and subclinical retinal detachments were found in the eyes cooled with 2 C fluid. Extreme cooling of eyes is not advisable, although temperatures of 22 C are well tolerated.

Animals↗