Marilyn C. Kincaid

Vancomycin Levels in the Vitreous Cavity After Intravenous Administration

PURPOSE We studied the effects of inflammation, repeated antibiotic doses, and the surgical status of the eye on penetration of vancomycin hydrochloride into the rabbit vitreous cavity after intravenous administration. METHODS We studied three anatomic states (phakic, aphakic, and aphakic, vitrectomy-treated eyes) subdividing each into inflamed and noninflamed groups. Intravenous vancomycin hydrochloride (15 mg/kg of body weight) was administered every 12 hours for 48 hours. Eyes were harvested for the assay of vitreous cavity antibiotic levels at various intervals from one to 49 hours. We determined concentrations and calculated mean values and S.E.M. RESULTS Therapeutic levels were not established in the vitreous cavity at any time period in the two phakic groups. At 25 hours, the inflamed aphakic eyes had concentrations of 5.05 +/- 1.9 micrograms/ml and the control noninflamed aphakic eyes 4.5 +/- 1.23 micrograms/ml; slight increases were found by 49 hours. Concentrations tested in the aphakic, vitrectomy-treated eyes at two, 13, 25, and 49 hours demonstrated progressive increases both in the inflamed eyes (5.4 +/- 2.4 micrograms/ml, 9.64 +/- 4.25 micrograms/ml, 9.2 +/- 3.96 micrograms/ml, 10.34 +/- 4.49 micrograms/ml) and noninflamed eyes (3.52 +/- 2.1 micrograms/ml, 5.4 +/- 1.96 micrograms/ml, 6.8 +/- 2.53 micrograms/ml, 8.7 +/- 5.44 micrograms/ml). CONCLUSIONS Vitreous vancomycin concentrations in aphakic and aphakic, vitrectomy-treated eyes after intravenous administration exceed the minimal inhibitory concentrations for the usual gram-positive pathogens that create endophthalmitis, suggesting a role for intravenous vancomycin in the treatment of bacterial endophthalmitis.

Vitreous cavity penetration of ceftazidime after intravenous administration

Purpose: Penetration of ceftazidime, a third generation cephalosporin, into the vitreous cavity after intravenous administration was investigated. Methods: Because antimicrobial penetration varies with surgical status of the eye and with inflammation, studies were conducted in phakic, aphakic, and aphakic, vitrectomized eyes in both normal and inflamed conditions. Ceftazidime 50 mg/kg was administered every 8 hours and vitreous cavity concentrations were tested at intervals from 2 to 72 hours after the initial dose. Results: No penetration was found into control phakic and aphakic eyes, but drug concentrations were detected in inflamed eyes at 24 hours. Vitreous concentrations of ceftazidime in aphakic, vitrectomized eyes reached levels well above the minimal inhibitory concentration (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in control eyes (8.5 µg/ml) and inflamed eyes (35.4 µg/ml). Inflammation and removal of the lens and vitreous significantly enhanced ceftazidime penetration at all time periods tested. Conclusion: Ceftazidime penetrates into the vitreous cavity of inflamed eyes after intravenous administration and achieves concentrations above the MIC for Pseudomonas organisms. Penetration is greatest in aphakic, vitrectomized eyes.

Vancomycin levels after intravitreal injection: Effects of inflammation and surgery

Objective: Vancomycin hydrochloride for intraocular injection is the drug of choice for the treatment of suspected gram‐positive endophthalmitis. To study its intraocular pharmacokinetics, we injected vancomycin into the vitreous cavity of phakic, aphakic, and aphakic‐vitrectomized rabbit eyes and determined its rate of clearance. Inflamed eyes were compared to control eyes in each group. Methods: Three groups of eyes were prepared. The eyes in Group 1 were phakic, the eyes in Group 2 had the lens removed, and the eyes in Group 3 had both the lens and central vitreous removed. Each group was subdivided into a control group and a group made inflamed by injection of heat‐killed Staphylococcus epidermidis. Vancomycin hydrochloride 1 mg in 0.1 cc of diluent was injected into the midvitreous cavity and samples obtained at 2 or 3, 8, 24, and 48 hours after injection. Vancomycin concentrations were measured and clearance rates were calculated for each of the groups. Results: Vancomycin was cleared substantially faster from aphakic‐vitrectomized eyes (half‐life 9.0 hours) and aphakic eyes (half‐life 8.9 hours) than phakic eyes (half‐life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group. Conclusions: Clearance of vancomycin from the phakic eye is prolonged compared to that of beta‐lactam antibiotics, an important pharmacokinetic advantage in treating endophthalmitis. Its clearance from aphakic‐vitrectomized eyes is dramatically faster than from phakic eyes and is similar to that of other antimicrobial agents.

Orbital solitary fibrous tumor: radiographic and histopathologic correlations.

OBJECTIVE To correlate the clinicopathologic and radiographic features characteristic of orbital solitary fibrous tumor (SFT). METHODS The diagnostic features and clinical outcome of seven adults with orbital SFT are retrospectively outlined. Orbital imaging was performed by ultrasonography, computed tomography, or magnetic resonance imaging. Some cases were imaged by multiple modalities. Histopathologic examination of each tumor specimen included standard light and immunohistochemical stains. RESULTS Heterogeneous internal composition was better appreciated on magnetic resonance imaging than on computed tomography. All cases undergoing magnetic resonance imaging showed T1 isointensity and T2 hypointensity relative to gray matter. Strong, generalized immunohistochemical reactivity to vimentin and CD34 validated the diagnosis of SFT and differentiated the specimens from other spindle cell neoplasms. After complete tumor resection, our patients remain tumor free with postoperative intervals of 15 to 45 months. CONCLUSIONS Solitary fibrous tumor has now been reported in 26 orbits. No physical finding is pathognomonic, but several imaging traits are highly characteristic. Intralesional image heterogeneity and a predominantly low T2 signal intensity are distinctive of SFT. Complete tumor resection and immunohistologic specimen evaluation are emphasized. Clinicians should consider the diagnosis of SFT when confronted with an adult patient having an orbital soft tissue mass demonstrating the distinctive magnetic resonance imaging findings.

Recurrent corneal erosion: pathology of corneal puncture.

Despite conventional therapy, some patients continue to have episodes of erosion. Recent literature suggests the efficacy of corneal puncture, which is thought to induce adherence of the epithelium and basement membrane to the anterior stroma. We performed multiple corneal punctures with 23-, 25-, 27-, and 30-gauge needles on one patient who underwent penetrating keratoplasty 7 weeks later. We found that an insertion depth of 0.1 mm was sufficient to cause the production of new basement membrane and fibrocytic reaction in the anterior stroma. Analysis of the pathologic specimen supports the use of the larger 23- and 25-gauge needles, and cautions against the use of small gauge needles, especially 30-gauge, for this procedure.

Aminoglycoside levels in the rabbit vitreous cavity after intravenous administration

PURPOSE To determine the penetration of gentamicin and amikacin into the rabbit vitreous cavity after their intravenous administration. METHODS Gentamicin (1.6 mg/kg every 8 hours) and amikacin (6 mg/kg every 12 hours) were administered intravenously to 25 rabbits that had previously had the lens and vitreous removed from 43 eyes. For each drug, ocular inflammation was induced in one group of eyes by injection of heat-killed Staphylococcus epidermidis, while the other group was maintained as a control. Samples from the vitreous cavity were taken at regular intervals for 72 hours after beginning the intravenous medications and were analyzed for drug concentrations. RESULTS The maximum intravitreal concentration +/- SD achieved for gentamicin was 1.8 +/- 0.5 microgram/ml. The maximum intravitreal concentration for amikacin was 8.5 +/- 3.2 micrograms/ml. Inflamed eyes demonstrated higher concentrations than did those without inflammation. CONCLUSIONS In a rabbit model with conditions optimized to enhance penetration of antimicrobials into the vitreous cavity after intravenous administration, neither gentamicin nor amikacin penetrated sufficiently to reach potentially therapeutic concentrations consistently for either Pseudomonas or S epidermidis organisms.

Intraocular injection of ceftazidime: Effects of inflammation and surgery

Objective: The clearance of ceftazidime from the rabbit vitreous cavity after injection into phakic, aphakic, and aphakic vitrectomized rabbit eyes was assessed and the duration of concentrations above the minimal inhibitory concentrations for target gram‐negative bacteria was determined. To determine the effect of inflammation on the intraocular pharmacokinetics of ceftazidime, each anatomic group was subdivided into inflamed and control eyes. Methods: Ceftazidime (2.25 mg) was into the vitreous cavity of inflamed and control rabbit eyes and its concentration was assayed 2, 8, 24, and 48 hours later. The half‐life for each of the anatomic groups was calculated. Results: The half‐life of ceftazidime in control phakic eyes was 13.8 hours. In aphakic eyes the half‐life was 11.8 hours and in the aphakic vitrectomized eyes the half‐life was 4.7 hours. Inflammation slightly shortened the half‐life in phakic (10.1 hours) and aphakic (8.7 hours) eyes. The half‐life in aphakic vitrectomized inflamed eyes was 5.1 hours. Conclusion: Vitrectomy and lensectomy significantly shorten the half‐life of ceftazidime after intravitreal injection. Inflammation increases clearance to a small degree in phakic and aphakic eyes.

Invasive squamous cell carcinoma arising from asymptomatic choristomatous cysts of the orbit: Two cases and a review of the literature

BACKGROUND Epithelial choristomatous cysts are common orbital lesions, the most frequent of which are dermoid or epidermoid tumors. Massive enlargement or extraorbital extension of these benign lesions may occur. Malignant transformation of the epithelial lining of epidermoid cysts is rarely reported. METHODS Two patients are presented in whom the epithelial lining of a previously asymptomatic choristomatous cyst of the orbit underwent malignant transformation to produce invasive squamous cell carcinoma. The unusual origin and clinical presentation of the lesions caused a delay in the diagnosis and therapy in both patients. Metastatic workup was negative in both patients, who underwent resection of their tumors via orbital exenteration with craniofacial resection. Reported cases of malignant transformation in analogous choristomatous cysts elsewhere in the cranium are reviewed. RESULTS One patient is alive and well without recurrent disease 40 months postoperatively. The second patient died of a pulmonary embolus 2 months postoperatively. Autopsy showed no residual tumor. Overall, only 3 of 18 reported patients with epidermoid choristoma of the head and orbit with malignant transformation were alive when reported. CONCLUSIONS Malignant squamous metaplasia is believed to be a rare complication of orbital dermoid or epidermoid cysts, with only two previously reported cases. However, malignant transformation is relatively frequent in analogous epidermoid cysts found elsewhere in the cranial vault, especially after incomplete excision. These reports encourage the complete removal of epithelial choristomas of the orbit.

Diffuse malignant change in a ciliochoroidal melanocytoma in a patient of mixed racial background.

A 69-year-old man of mixed racial background was discovered to have a large, deeply pigmented mass in his left eye with a history of rapid growth during the previous 6 months. The eye was enucleated, and histopathological examination revealed an epithelioid malignant melanoma arising from a melanocytoma.

Histological and radiological analyses of hydroxyapatite orbital implants in rabbits.

Summary To date, only anectodal clinical data exist pertaining to the histological changes of hydroxyapatite within an enucleated socket. This study was conducted to determine the histological and radiological changes in a coralline hydroxyapatite sphere placed into the central socket, in a controlled fashion. Rabbits underwent simple enucleation with implantation of an autologous sclera-wrapped hydroxyapatite spheres with extraocular muscle reattachment. Preoperatively, the mineral density of each sphere was determined using quantitative computed tomography (CT) that was repeated 2− and 6 weeks postoperatively. The implants were harvested at 2− and 6 weeks and submitted for light and electron microscopic analysis. The results demonstrated a uniform influx of fibrovascular tissue that did not reach the center of the implant, even at 6 weeks. A marked mixed-cell inflammatory response was noted at the interface between the fibrovascular tissue and the hydroxyapatite. Giant cells were noted only at the scierai windows. This study demonstrated that the early response to hydroxyapatite implants was fibrovascular ingrowth with mixed-cell inflammation. These histological observations correlated with findings observed with quantitative CT. Quantitative CT appears to be an ideal modality for observing the early temporal tissue density changes in hydroxyapatite implants.