Intact Vitreous Research Articles

Radiotherapy-induced alterations in vitreous humor: A new potential critical structure

Vitreous humor (VH) is not considered as a critical structure in the radiotherapy planning process. In the present study, an experimental animal model was performed to examine the effects of radiotherapy on VH.The right eyes of twelve New Zealand rabbits were irradiated to 60 Gy in 3 fractions in accordance with the scheme used in the treatment of uveal melanoma in our clinic, and contralateral (left) eyes were considered as control. Weekly ophthalmologic examination was performed after irradiation, for three months. At the end of the third month, enucleation and vitreous collection were conducted. The vitreous samples were subjected to metabolomic analyses, ELISA analyses, viscosity measurements, and electron microscopic examination.In control and experimental vitreous samples, 275 different metabolites were identified, and 34 were found to differ significantly between groups. In multivariate analyzes, a clear distinction was observed between control and irradiated vitreous samples. Pathway analysis revealed that nine pathways were affected, and these pathways were mainly related to amino acid metabolism. A significant decrease was observed in the expressions of type II, V, and XI collagens in protein level in the ELISA. There was a non-significant decrease in type IX collagen and viscosity. Electron microscopic examination revealed disrupted collagen fibrillar ultra-structure and dispersed collagen fragments in the experimental vitreous.An intact vitreous is essential for a healthy eye. In this study, we observed that radiation causes changes in the vitreous that may have long-term consequences.

Vitreous VEGF Clearance Is Increased after Vitrectomy

Purpose. Pars plana vitrectomy (PPV) has been reported to reduce macular thickness and improve visual acuity in patients with diabetic macular edema (ME). The hypothesis for the study was that after PPV, clearance is accelerated and VEGF concentrations are reduced. To test this hypothesis, hVEGF(165) injections were performed in rabbit eyes, with and without PPV, and vitreous VEGF levels were measured as a function of time. Methods. The PPV group rabbits had a bilateral 25-gauge PPV, and in the no-PPV group, rabbits had intact vitreous. Intravitreal injections of hVEGF(165) were performed, and the animals were euthanatized at time points up to 7 days. The vitreous was isolated and an enzyme-linked immunosorbent assay was used to measure the VEGF levels. Pharmacokinetic parameters were determined in a noncompartmental analysis approach. Results. Mean vitreous VEGF levels decreased more rapidly in eyes subjected to PPV than in no-PPV eyes. The vitreous VEGF half-life (t([)(1/2)(])) in PPV eyes was 10 times shorter than that in normal eyes. In addition, mean clearance and mean area under the curve (AUC) increased and decreased, respectively, in eyes that underwent PPV. Conclusions. VEGF clearance is increased after PPV. Reducing VEGF concentrations in the vitreous post-PPV may partially explain the improvement in macular thickness in some patients with ME. Unexpectedly, the half-life of VEGF in the vitreous, even in no-PPV eyes, was <3 hours, whereas compounds of similar molecular weight typically have longer vitreous half-lives. The back of the eye may be uniquely adapted with rapid-clearance mechanisms to regulate vitreous VEGF levels. Further study is suggested.

Posterior vertical capsulotomy with optic entrapment of the intraocular lens in congenital cataracts—prevention of capsule opacification

To present a modified surgical technique for preventing posterior capsule opacification (PCO) in children with congenital cataracts and to evaluate its long-term efficacy. Department of Ophthalmology, Medical University of Southern Africa, Medunsa, South Africa. Anterior and posterior vertical capsulotomy, with optic entrapment of the intraocular lens (IOL) by maintaining the anterior hyaloid, was performed in 68 cataractous eyes of children aged 2 months to 8 years (mean 3 years, 1 month). The posterior capsule was evaluated for at least 5 years for secondary opacification, IOL position, pigmentary deposits on the IOL optic, and the presence of synechias. Sixty-eight eyes maintained a clear visual axis for 5 to 12 years (mean 9 years, 1 month) postoperatively. No secondary procedure was necessary. In all eyes, the IOL remained well centered and entrapped. Posterior capsulotomy with optic entrapment of the IOL proved to be a safe and efficient surgical procedure for preventing PCO in children with congenital cataracts. Uniting the anterior and posterior capsule in front of the IOL limits the proliferation and migration of Elschnig pearls. An intact anterior hyaloid does not induce capsule opacification in association with optic entrapment; therefore, a vitrectomy is not indicated even in infants under age 5 years. Clear visual axis, centered IOL, and intact vitreous were achieved in this series; this enables a promising long-term prognosis for binocular visual development, especially because surgery was performed early.

OFLOXACIN PENETRATION INTO THE EYE AFTER INTRAVENOUS AND TOPICAL ADMINISTRATION

Purpose: To determine the aqueous and vitreous fluid penetration of ofloxacin after a combined topical and single intravenous dose protocol before vitrectomy surgery. Materials and Methods: Before undergoing vitrectomy surgery, patients were given two drops of ofloxacin 0.3% topically and a single intravenous dose of ofloxacin 400 mg. Aqueous (mean, 43 minutes) and vitreous (mean, 53 minutes) fluid samples were collected at the start of the surgical procedure. The samples were analyzed for ofloxacin penetration. Results: The mean aqueous fluid concentration was 1.083 μg/mL ± 0.406. The mean ± SD vitreous fluid concentration in nondiabetic patients with intact vitreous was 0.352 μg/mL ± 0.301. Vitreous levels obtained more than 50 minutes after administration (0.414 μg/mL ± 0.336) were generally higher than those obtained after less than 50 minutes (P = 0.12). Eyes with prior vitrectomies achieved better ofloxacin penetration (0.984 μ/g/mL ± 0.680) than did nonvitrectomized eyes. Conclusion: Ofloxacin achieved measurable aqueous fluid penetration after topical and intravenous administration. Aqueous levels were above the minimum inhibitory concentration for most ocular pathogens. Vitreous levels were adequate in vitrectomized eyes to achieve inhibitory concentrations against many common ocular pathogens. Combined preoperative topical and a single dose of intravenous ofloxacin may provide inhibitory aqueous and vitreous antibiotic levels in vitrectomized eyes in cases where intravitreal antibiotics are not considered and oral administration is not practical. RETINA 17:535-539, 1997

Ofloxacin penetration into the eye after intravenous and topical administration

To determine the aqueous and vitreous fluid penetration of ofloxacin after a combined topical and single intravenous dose protocol before vitrectomy surgery. Before undergoing vitrectomy surgery, patients were given two drops of ofloxacin 0.3% topically and a single intravenous dose of ofloxacin 400 mg. Aqueous (mean, 43 minutes) and vitreous (mean, 53 minutes) fluid samples were collected at the start of the surgical procedure. The samples were analyzed for ofloxacin penetration. The mean aqueous fluid concentration was 1.083 micrograms/mL +/- 0.406. The mean +/- SD vitreous fluid concentration in nondiabetic patients with intact vitreous was 0.352 microgram/mL +/- 0.301. Vitreous levels obtained more than 50 minutes after administration (0.414 microgram/mL +/- 0.336) were generally higher than those obtained after less than 50 minutes (P = 0.12). Eyes with prior vitrectomies achieved better ofloxacin penetration (0.984 microgram/mL +/- 0.680) than did nonvitrectomized eyes. Ofloxacin achieved measurable aqueous fluid penetration after topical and intravenous administration. Aqueous levels were above the minimum inhibitory concentration for most ocular pathogens. Vitreous levels were adequate in vitrectomized eyes to achieve inhibitory concentrations against many common ocular pathogens. Combined preoperative topical and a single dose of intravenous ofloxacin may provide inhibitory aqueous and vitreous antibiotic levels in vitrectomized eyes in cases where intravitreal antibiotics are not considered and oral administration is not practical.

Treatment of experimental vitreous hemorrhage with tissue plasminogen activator

Tissue plasminogen activator(tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of hyphema. Intravitreal injection of tPA can promote rapid lysis of experimental intravitreal fibrin clots. The purpose of this study was to investigate the efficacy of intravitreal tPA injection for the treatment of vitreous hemorrhage in normal phakic non-vitrectomized rabbit eyes. Vitreous hemorrhages were produced by intravitreal injections of 0.05 ml of autologous whole blood in 25 rabbit eyes with intact vitreous. The injection of 25 or 100 micrograms of tPA in 15 eyes resulted in the clearance of vitreous hemorrhage in 99 +/- 19 or 34 +/- 6.5 days, respectively. This was significantly faster than in the control eyes in which the clearance was not seen until 131 +/- 17 days later. No tractional retinal detachment was observed.

Panretinal photocoagulation aggravates experimental proliferative vitreoretinopathy

The effects of panretinal photocoagulation (PRP) on intravitreal proliferation were evaluated in an experimental model for proliferative vitreoretinopathy (PVR). Thirty-three pigmented rabbits underwent argon laser PRP in one eye. Cultured fibroblasts (2 x 10(5) or 4 x 10(5) cells) were implanted into the intact vitreous of both eyes of each animal either 3 days after PRP (when acute laser lesions were present) or 4 weeks after PRP (scarred laser lesions). PVR was assessed by indirect ophthalmoscopy for 4-8 weeks. Histological examination included staining with monoclonal antibodies against glial fibrillary acidic protein (GFAP). In both groups significantly more severe stages of PVR developed after PRP than in the controls. Total retinal detachments ensued in 13 photocoagulated eyes versus five controls. PRP induced invasion of macrophages, proliferation of retinal pigment epithelium and a conspicuous Müller cell response, enhancing intraocular inflammation, which stimulated intravitreal proliferation and aggravated PVR.

Naka-Rushton equation parameters in electroretinogram analysis of daunomycin effects on retinal function

Intraocular daunomycin may inhibit intravitreal cellular proliferation in proliferative vitreoretinopathy after rhegmatogenous retinal detachments and retinal reattachment surgery. Doses of 15 nmol or more have shown histological retinal toxicity when injected into the intact vitreous of rabbit eyes. We injected 30, 20, 10 and 0 nmol doses of daunomycin into rabbit eyes with gas-compressed vitreous to better simulate the clinical conditions in which it would be used. We then evaluated effects on retinal function by examining scotopic b-wave amplitudes, measured for a four log unit set of intensities. We used the three independent parameters Rmax, log K, and n of the Naka-Rushton equation to measure changes in retinal function. All three doses of daunomycin failed to measurably depress retinal function (i.e., there were no dose-related losses of Rmax, log K or n) in this experimental model. We used this approach to monitor alterations in retinal function since it can show selective changes in each parameter. This selectivity is an advantage over monitoring retinal function with single intensities or comparisons limited solely to electroretinogram amplitudes.

Prediction of the Kinetics of Disappearance of Sulfur Hexafluoride and Perfluoropropane Intraocular Gas Bubbles

Intravitreal gases are useful in treating complicated retinal detachments by providing internal tamponade of retinal breaks. The geometry of the intraocular gas bubble and the kinetics of intraocular gas absorption determine the geometry and duration of internal tamponade of the retinal break. The authors derived a mathematical relationship based on a geometric model of the rabbit eye which allows calculation of the volume of an intraocular gas bubble from its observed meniscus height. When compared with actual measured bubble volumes, this technique was found to provide an accurate, noninvasive method for determining true intraocular gas volumes. Using this model, the absorption of nonexpansile concentrations of sulfur hexafluoride (SF6) and perfluoropropane (C3F8) were found to obey first-order kinetics. Both gases were found to have an intraocular half-life two to three times shorter in aphakic rabbit eyes after total vitrectomy than in phakic rabbit eyes with intact vitreous.

Treatment of Experimental Intravitreal Fibrin with Tissue Plasminogen Activator

We produced experimental intravitreal fibrin clots in rabbits that had previous gas compression of the vitreous or intact vitreous. Twenty-four hours after production of fibrin, the eyes were injected with 25 micrograms of tissue plasminogen activator or physiologic irrigation solution. In the gas compression group (n = 11), all tissue plasminogen activator-treated eyes cleared within six hours of injection; complete clearing was not seen until six days in the physiologic irrigation solution-treated eyes (n = 9). A similar response was seen in the intact vitreous group. No evidence of toxicity was observed as measured by slit-lamp biomicroscopy, intraocular pressure, corneal thickness, electroretinography, or histopathologic examination.

A refined experimental model for proliferative vitreoretinopathy

Animal models of proliferative vitreoretinopathy (PVR) in which the intact vitreous is injected with large numbers of tissue cultured fibroblasts do not accurately represent the disease as it is found in humans. A refined model of PVR is presented, in which the vitreous is compressed and partially detached using intravitreally injected perfluorpropane, followed by injection of 25,000 homologous fibroblasts. Proliferation occurred on the retinal surface, causing retinal detachments with the same frequency as models using greater numbers of cells.

The Effect of Triamcinolone Acetonide on a Refined Experimental Model of Proliferative Vitreoretinopathy

Animal models of proliferative vitreoretinopathy in which the intact vitreous body is injected with large numbers of fibroblasts do not resemble the human situation. Using a refined rabbit model of proliferative vitreoretinopathy in which the vitreous is compressed and partially detached from the retinal surface and small amounts of tissue-cultured homologous fibroblasts (25,000) are scattered over the vascularized part of the retina, we reevaluated the effect of intravitreally injected triamcinolone acetonide. We found that 2 mg of the corticosteroid reduced the incidence of retinal detachments from 90% to 56%. The effect was less than in previous models with intact vitreous. Large doses of the corticosteroid had no additional effect on the reduction of retinal detachments, indicating an optimal dosage of 2 mg. The effect of the corticosteroid on neovascularization was considerable; with 8 mg it could almost be prevented (reduction from 74% to 8%).