Robert Machemer

The Classification of Retinal Detachment with Proliferative Vitreoretinopathy

The term proliferative vitreoretinopathy (PVR) is proposed as a designation for the clinical condition previously known variously as massive vitreous retraction, massive preretinal retraction, or massive periretinal proliferation. This is an abnormality in which rhegmatogenous retinal detachment is complicated by proliferation of membranes on both surfaces of the detached retina and on the posterior surface of the detached vitreous gel. The new classification subdivides PVR into four stages: A, minimal; B, moderate; C, marked; and D, massive. The extent of the fixed retinal folds is subdivided to indicate the number of involved quadrants. The degree of retinal shrinkage into a funnel-like configuration is subdivided into three grades.

An updated classification of retinal detachment with proliferative vitreoretinopathy.

Abstract The Retina 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.

Treatment of Intraocular Proliferation with Intravitreal Injection of Triamcinolone Acetonide

We studied the inhibitory effect of triamcinolone acetonide on experimental intraocular proliferation. Autotransplantation of fibroblasts from rabbit rump skin into the vitreous cavity resulted in intravitreal strand formation and traction retinal detachment in 36 of 43 eyes (84%) over a period of three months. A single intravitreal injection of 1 mg of triamcinolone acetonide inhibited fibroblast growth and significantly reduced the number of retinal detachments in 15 of 44 eyes (34%). Retinal neovascularization caused by fibrous strands coming into contact with vacularized retina was also reduced by triamcinolone acetonide (31 of 43 control eyes [72%] vs eight of 44 treated eyes [18%]). Intravitreal corticosteroid therapy may be an important adjunct to the therapy of perforating injuries and massive periretinal proliferation.

Pigment Epithelial Proliferation in Human Retinal Detachment with Massive Periretinal Proliferation

Biopsy specimens from vitreous and preretinal membranes, obtained during vitreous surgery from 39 human eyes suffering from massive periretinal proliferation, were examined electron-microscopically. Analysis of the cellular membranes demonstrated mostly cells with epithelial characteristics: polarization of the cells, basal lamina formation, specialized cellular junctions, and microvilli formation. These epithelioid cells contained prominent rough endoplasmic reticulum, glycogen deposits, a multitude of cytoplasmic filaments, some resembling myofilaments, and nonmembrane bound, sometimes wedge-shaped pigment granules. Macrophages were interspersed in the membranes. There was a striking similarity of these findings to those of an experimental model of retinal detachment in owl monkeys, We concluded that most likely the described cells derived from cells of pigment epithelial origin.

The Lack of Toxicity of Intravitreally Administered Triamcinolone Acetonide

We gave one eye of each 21 rabbits an intravitreal injection of 1 mg of triamcinolone acetonide; the other eye received an injection of an equal volume of saline solution as a control. Results of slit-lamp examinations, ophthalmoscopy, intraocular pressure, electroretinography, and light electron microscopy all remained normal throughout the three-month course of the experiment, demonstrating the lack of ocular toxicity of triamcinolone acetonide in the rabbit.

Experimental Subretinal Hemorrhage in Rabbits

In order to simulate the hemorrhagic detachment stage of disciform macular degeneration, we injected fresh autologous blood into the subretinal space of albino rabbits and studied these hemorrhages clinically with the ophthalmoscope and by light and electron microscopy. One hour after injection, retinal changes were minimal and limited to occasional photoreceptor edema. At one day, there was marked damage of the photoreceptor cells characterized by edema and disintegration of the photoreceptors and pyknosis of the outer nuclear layer. Some photoreceptors had been pulled off the retina by contraction or movement of the blood clot, or both. By seven days, the photoreceptor cells were almost absent. Subretinal hemorrhage in rabbits led to irreversible retinal destruction within 24 hours. We think that the mechanism of the destruction of the overlying retina consists of a combination of a diffusion barrier by the clot, mechanical damage to the outer segments by contraction of the clot, and iron toxicity.

Inhibition of Intraocular Proliferations with Intravitreal Corticosteriods

Autotransplantation of one fourth million tissue cultured fibroblasts from rabbit rump skin into the vitreous cavity resulted in intravitreal strand formation and traction retinal detachment (27 of 47 eyes, 57%). A single intravitreal injection of 1 mg of dexamethasone alcohol inhibited fibroblast growth as judged by the significantly reduced number of retinal detachments (11 of 46 eyes, 24%). Retinal neovascularization that was observed when fibrous strands came into contact with vascularized retina (nine of 47 eyes, 19%) was also inhibited after corticosteroid application (two of 46 eyes, 4%).

Experimental and Clinical Observations of the Intraocular Toxicity of Commercial Corticosteroid Preparations

We tested the vehicles of six different commercially available depot corticosteroids (Celestone Soluspan, Depo-Medrol, Decadron, Decadron L. A., Aristocort, and Kenalog) for possible toxicity when injected intravitreally. When tested on rabbit eyes, the Celestone Soluspan and the Depo-Medrol vehicles caused remarkable retinal degeneration with preretinal membrane formation or cataracts in their standard concentrations. Three other vehicles (Decadron and Decadron L. A.) caused localized retinal degeneration in twice the standard concentration. Thus, toxic effects can be caused by preservatives or inadequate osmolarity of the vehicles alone. The development of proliferative vitreoretinopathy in some cases of injections of intraocular depot corticosteroid can be explained by retinal necrosis and repair processes caused by these vehicles.

The Clearance of Intravitreal Triamcinolone Acetonide

Since high corticosteroid levels are important in achieving inhibition of intraocular cellular proliferation, we studied the clearance of an intravitreally injected slowly dissolving corticosteroid in the rabbit eye. Triamcinolone acetonide (0.5 mg) disappeared rapidly in eyes that underwent a combined vitrectomy and lensectomy (average, 6.5 days) and more slowly in eyes that underwent vitrectomy only (average, 16.8 days) compared with unoperated normal rabbit eyes (average, 41 days). The ophthalmoscopic disappearance of the white crystals correlated well with a sensitive colorimetric test for clearance of the corticosteroid. Direct observation is therefore an accurate method of assessing the absorption of the corticosteroid. If used therapeutically, this study suggests that more frequent injections of triamcinolone acetonide would be necessary in eyes that underwent vitrectomy, compared with normal eyes.

Vitreous Surgery for Hemorrhagic and Fibrous Complications of Age-Related Macular Degeneration

We applied vitreous surgical techniques in the treatment of hemorrhagic and fibrous complications of choroidal neovascular membranes by removing subretinal scars or hemorrhage, or both, in four patients. The surgical goals were achieved in all patients. Visual acuity improved in three patients. The major complication was recurrent detachment associated with large retinotomies.