Jonathan Shahar

Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin).

Purpose: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. Methods: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. Results: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. Conclusions: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Physiological and toxicological effects of cefuroxime on the albino rabbit retina.

PURPOSE Intracameral cefuroxime was found to lower the risk of endophthalmitis after cataract surgery. The purpose of this study was to evaluate the retinal toxicity of cefuroxime in a rabbit model. METHODS Twenty-two albino rabbits were divided into two cefuroxime groups: low-dose (1mg/0.1 mL, n = 9) and high dose (10 mg/0.1 mL, n = 13). The right eye of each rabbit was injected with 0.1 mL cefuroxime solution (experimental eye) and the left eye with 0.1 mL saline (control eye). Electroretinogram (ERG) responses were recorded at 3 hours, 4 days, and 1, 2, and 4 weeks after injection. After 4 weeks, the rabbits were euthanized, the eyes were enucleated, and the retinas were prepared for histologic evaluation and GFAP immunostaining. RESULTS No functional (ERG) or histologic damage was found in rabbits in the low-dose group. In the high-dose group, a significant decrease in the ERG amplitudes of the experimental eyes was seen 3 hours after injection, followed by partial recovery during 4 weeks of follow-up. Retinal histology of experimental eyes revealed marked damage. GFAP immunoreactivity in Müller cells was expressed in rabbits belonging to both groups, although it was more extensive in the high-dose group. CONCLUSIONS ERG and histologic findings indicated that a dose of 1 mg cefuroxime, administered intravitreally, was not toxic to the rabbit retina. A dose of 10 mg, injected intravitreally, induced transient physiological effects, and was toxic to the rabbit retina, as was evident by the permanent reduction in the ERG responses and by the structural damage to the retina with signs of glial activation.

Diameters of retinal blood vessels in a healthy cohort as measured by spectral domain optical coherence tomography.

Purpose: To describe a method for measuring the diameters of large retinal blood vessels by means of spectral domain optical coherence tomography. Methods: Prospective cohort study of 29 healthy subjects (58 eyes) who underwent a spectral domain optical coherence tomography examination. Two cubes of horizontal scans were placed at the superior and inferior borders of the disk to include the large temporal retinal vessels. Vessels diameters were measured, and an artery-to-vein ratio was calculated at 10 measurement points (480–1440 &mgr;m superiorly and inferiorly from the optic disk border). Results: The mean age of the study subjects was 41.45 ± 15.53 years. Patients had no ocular or systemic pathologies. The mean diameter of the retinal artery was 135.73 ± 15.64 &mgr;m and of the vein 151.32 ± 15.22 &mgr;m at the measurement point of 480 &mgr;m, with a gradual decrease to 123.01 ± 13.43 &mgr;m and 137.69 ± 13.84 &mgr;m, respectively, at 1440 &mgr;m. The artery-to-vein ratio was ∼0.9 at all points of measurement. Conclusion: This is a new noninvasive method for retinal blood vessels diameter measurement using the spectral domain optical coherence tomography imaging modality. This method may aid in evaluation of retinal and systemic vascular diseases.

Effect of Pupil Size on Biometry Measurements Using the IOLMaster

PURPOSE To evaluate the effect of pupil dilation on biometric measurements and intraocular lens power calculation using the IOLMaster (Carl Zeiss Meditec). DESIGN Prospective, observational case series. METHODS In this prospective study, 2 consecutive optical biometry measurements, before and after pupil dilation, were obtained using the IOLMaster on 318 eyes of 214 patients at the cataract presurgery clinic. The parameters compared were axial length, corneal power, cylinder, and the corresponding intraocular lens power, which was calculated using the Sanders-Retzlaff-Kraff/Theoretical formula. RESULTS This study found no statistically significant difference before and after dilation in axial length (0.005 mm; P = .476), corneal power (0.001 diopters [D]; P = .933), or calculated intraocular lens power (0.011 D; P = .609). A statistically significant difference was shown in cylinder measurements before and after dilation (0.102 D; P < .001). CONCLUSIONS This study demonstrated there is no clinically significant effect of pupil dilation on the IOLMaster measurements of axial length, corneal power, and corresponding theoretical intraocular lens power calculated using the Sanders-Retzlaff-Kraff/Theoretical formula.

Retinal toxicity of intravitreal rituximab in albino rabbits.

Purpose: To evaluate retinal toxicity of intravitreal rituximab. Methods: Twelve albino rabbits were included in the study. 1 mg/0.1 mL of rituximab was injected to the right (experimental) eye of each rabbit, and 0.1 mL of saline was injected into the left (control) eye. Electroretinogram was recorded before injection and 3 hours, 4 days, 1 week, 2 weeks and 4 weeks after injection (12 rabbits), and visual evoked potential was recorded before injection and 4 weeks after injection (10 rabbits). Histology and glial fibrillary acidic protein immunocytochemistry (12 rabbits) were performed at 4 weeks after injection. Clinical examination was conducted at all time points in all rabbits. Results: The average dark-adapted electroretinogram b-wave Vmax ratios, and the average light-adapted b-wave amplitude ratios were approximately 1, and the average log &sgr; difference was around zero throughout the follow-up period. The average visual evoked potential amplitude ratio and the average visual evoked potential implicit time difference were approximately 1 and 0, respectively. No histologic damage was seen, but glial fibrillary acidic protein was mildly expressed in 6 of 12 experimental eyes. Results of clinical examination were normal in all the eyes. Conclusion: Intravitreal injection of 1 mg rituximab does not cause functional or histologic signs of retinal toxicity in albino rabbits. Mild glial fibrillary acidic protein expression in Müller cells probably indicates a mild degree of retinal stress.