Walter H. Stern

Epidemic Postsurgical Candida Parapsilosis Endophthalmitis: Clinical Findings and Management of 15 Consecutive Cases

Fifteen cases of postoperative Candida parapsilosis endophthalmitis occurring secondary to a contaminated lot of an irrigating solution were studied. All patients underwent a vitreous tap or diagnostic and therapeutic vitrectomy. Eleven of the 15 specimens were positive for the organism. Fourteen patients were treated with pars plana vitrectomy surgery. All patients were treated with intravitreal amphotericin B and systemic amphotericin B and 5-fluorocytosine. Two clinical recurrences were successfully treated with intravitreal amphotericin B, removal of the pseudophakos, and oral ketoconazole. The intraocular lens was retained in 11 of the 14 pseudophakic patients. Final visual acuities ranged from 20/25 to no light perception with eight of 15 patients having 20/60 or better visual acuities. Measurable levels of intraocular amphotericin B were found after systemic amphotericin B administration. Two patients with totals of 20 and 30 micrograms of intravitreal amphotericin B over 48 and 96 hours, respectively, had near normal ERGs one year later. Posterior capsulotomy and vitrectomy appear to decrease amphotericin B toxicity and allow sequential intraocular injection of this drug within a short time period.

Fluorouracil therapy for proliferative vitreoretinopathy after vitrectomy.

Fluorouracil effectively inhibits epiretinal membrane formation and traction retinal detachment after vitrectomy surgery. When 0.5 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after the intraocular injection of 200,000 cultured retinal pigment epithelial cells occurred in 12 of 12 control eyes but in only six of 14 eyes treated with fluorouracil (P less than .001). Four weeks after cell injection, eight of 12 eyes treated with fluorouracil had traction retinal detachments whereas 12 of 12 control eyes did (P less than .001). The height of the traction retinal detachment four weeks after intraocular injection of 200,000 cultured retinal pigment epithelial cells was reduced 50% in eyes treated with 0.5 mg of fluorouracil every 24 hours for seven days compared to control eyes (P less than .001). When the number of injected retinal pigment epithelial cells was increased to 400,000 cells and 1.25 mg of fluorouracil was administered intraocularly every 24 hours for seven days, traction retinal detachment two weeks after injection occurred in 15 of 15 eyes in the control group but in none of ten eyes in the treated group. Four weeks after cell injection, eight of eight eyes in the control group and five of five eyes in the fluorouracil-treated group had detachments and the mean height of the detachments in the two groups was equal. Autoradiography of the epiretinal membranes in eyes injected with 200,000 cultured retinal pigment epithelial cells and labeled for two hours with tritiated thymidine showed that 0.8% of the epiretinal cell nuclei were labeled two weeks after cell injection but that no labeled cells were present in the fluorouracil-treated eyes. Tritiated thymidine labeling of epiretinal cells in the fluorouracil-treated eyes was first noted three weeks after the cell injection. The presence of tritiated thymidine labeling in the fluorouracil-treated eyes correlated with an increase in the number of epiretinal cells and an increase in the incidence of traction retinal detachment.

Ocular Toxicity of Fluorouracil after Vitrectomy

The retinal and corneal toxicity of fluorouracil in the rabbit eye after lensectomy and vitrectomy depended on both the dosage and the frequency of intraocular injection and was reversible at certain dosages. All eyes in Group 1 (1.25 mg of fluorouracil every 12 hours for four days and then every 24 hours for three days) had opaque corneas by three days; these did not clear for four weeks. Histologic studies showed loss of photoreceptor outer segments and loss of ribosomes in all the retinal cells examined. The electroretinographic b-wave decreased to 0% of the baseline value (no b-wave), and did not recover after three weeks. In Group 2 eyes (1.25 mg of fluorouracil every 24 hours for seven days), corneal opacification increased to a maximum after two weeks and gradually decreased by four weeks. The electroretinographic b-wave diminished to 9.6% of the baseline value at two weeks but later recovered to 62.5% of the baseline value at three weeks. Histologic studies showed loss of photoreceptor outer segments and ribosomes at nine days; both returned to near normal after five weeks. Clinical, electrophysiologic, and histologic studies showed no toxicity in Group 3 eyes (0.5 mg of fluorouracil every 24 hours for seven days). This dosage of fluorouracil exerts a significant antiproliferative effect on injected retinal pigment epithelial cells and is well tolerated by the rabbit eye.

Classification of Proliferative Vitreoretinopathy Used in the Silicone Study

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.

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.

The Role of Hypersensitivity Reactions to Toxoplasma Antigens in Experimental Ocular Toxoplasmosis in Nonhuman Primates

To assess the role of ocular hypersensitivity reactions to Toxoplasma antigens in previously sensitized ocular tissues, we used a nonhuman primate model of ocular toxoplasmosis. Each eye of eight monkeys was inoculated with living Toxoplasma organisms into the inner retinal layers. All eyes developed necrotizing retinochoroiditis. Healing of the lesion occurred with the formation of a retinochoroiditic scar. Four months later, Toxoplasma antigens were injected through the right internal carotid artery. Four weeks after this, Toxoplasma antigens were inoculated into the left retina. Iritis, vitritis, and retinal edema occurred in response to the administration of the antigens, but no recurrent necrotizing retinochoroiditis was produced in this model. These findings suggested that hypersensitivity to Toxoplasma antigens does not play a major role in triggering recurrences of toxoplasmic retinochoroiditis in nonhuman primates.

Postoperative Mycobacterial Endophthalmitis

We treated two sporadic cases of postoperative endophthalmitis caused by rapidly growing (Runyons 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.

Epiretinal Membrane Formation after Vitrectomy

Our experimental model of epiretinal membrane formation in the rabbit eye after lensectomy and vitrectomy provides a way of studying pharmacologic and surgical approaches to inhibiting epiretinal cellular proliferation and contraction in the eye that has undergone vitrectomy. We injected 400,000 tissue-cultured retinal pigment epithelial cells onto the retinal surface of rabbit eyes that had undergone lensectomy, vitrectomy, and fluid-gas exchange. By one week, a funnel-shaped detachment of the medullary rays had occurred in 100% of the injected eyes. Histologically, the cells formed an epiretinal membrane by six hours after injection and caused major wrinkling of the inner retina after 24 to 48 hours. The percentage of tritiated-thymidine-labeled epiretinal cells increased dramatically 24 hours after injection and then declined. Cellular membranes bridging the optic nerve, followed by growth and contraction of the epiretinal cells on the detached internal limiting membrane, were responsible for the closed funnel appearance of the medullary rays.

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 Wegeners 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.

Methods, statistical features, and baseline results of a standardized, multicentered ophthalmologic surgical trial: The silicone study

This article describes the trial design and baseline results for the Silicone Study, a multicenter, randomized surgical trial designed to compare the effectiveness of silicone fluid versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR). Design features include (1) standardization of the surgical protocol to reduce intersurgeon variability, (2) formulation of a PVR clinical classification system relevant to modern vitreoretinal surgery, and (3) creation of a photographic protocol to document PVR pathology. Statistical issues affecting the analysis of the outcome data include (1) the addition of a second group of patients with more severely diseased eyes after the trial began, (2) the change to a different long-acting gas during the course of the trial, and (3) recurrent retinal detachments that require reoperations with the randomized treatment, and, in some instances, a crossover from the randomized to the alternate treatment. Demographic and baseline ocular characteristics are presented for the two groups under study.