Iryna Falkenstein

Changes of intraocular pressure after intravitreal injection of bevacizumab (avastin).

Purpose: To determine changes and need to monitor intraocular pressure (IOP) following intravitreal injection of bevacizumab (Avastin). Methods: Seventy patients (122 injections) underwent an intravitreal injection of Avastin for exudative age-related macular degeneration treatment. Forty-one eyes (59%) had single injection, 29 eyes (41%) had repeated injections. IOP was measured before and after Avastin injection at 3, 10, and 15 minutes. Twenty-nine eyes were evaluated for baseline IOP changes after multiple injections. Statistical analysis was performed. Results: Baseline mean IOP was 15.17 ± 3.42 mm Hg, with range from 08 mm Hg to 23 mm Hg. Postinjection 3 minutes the IOP had risen to a mean of 36.27 ± 5.1 mm Hg and fell spontaneously to a mean of 24.56 ± 5.9 mm Hg at 10 minutes. Ten eyes (14%) needed 15 minutes to drop below 30 mm Hg. All eyes were below 30 mm Hg at 15 minutes. No significant change between multiple baseline IOP measurements was detected. Conclusion: Avastin injections caused a predictable probably volume-related rise in IOP which never occluded the central retinal artery and which spontaneously fell to below 30 mm Hg in all eyes within 15 minutes. This strong safety profile provides guidelines on monitoring IOP after Avastin injections. There was no IOP change after multiple injections.

Intravitreal properties of porous silicon photonic crystals: a potential self-reporting intraocular drug-delivery vehicle.

Aim: To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. Methods: A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. Results: No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion: The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.

Discrepancy between fluorescein angiography and optical coherence tomography in detection of macular disease.

Purpose: To compare high-resolution optical coherence tomography (OCT) and fluorescein angiography (FA) in detection of macular edema (ME) of various etiologies. Methods: In a retrospective study over a 12-month period at one retina center, data for consecutive eyes that had undergone simultaneous conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients underwent additional examination with extremely high-resolution (6-&mgr;m)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc., Toronto, Ontario, Canada). Results: Of 1,272 eyes, 1,208 (94.97%) had the finding of ME or subretinal fluid confirmed by both techniques. There were 49 eyes (3.86%) for which FA showed dye leakage in the macular area and OCT showed normal foveal contour. Of 10 eyes in this group that underwent imaging with ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and subretinal fluid, which was missed by FA. Conclusions: Both FA and high-resolution OCT are highly sensitive techniques and correlate well in detection of ME. However, there is a small chance that when performed alone they might miss existing subtle ME.

Standardized Visual Acuity Results Associated With Primary Versus Secondary Bevacizumab (avastin) Treatment For Choroidal Neovascularization In Age-related Macular Degeneration

Purpose: To compare standardized visual outcomes and macular thickness changes associated with primary and secondary bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods: Eighteen eyes received primary bevacizumab treatment; 20 eyes received pegaptanib (Macugen; Eyetech/OSI Pharmaceuticals, New York, NY) as initial treatment followed by bevacizumab therapy. Both medications were injected at 6-week intervals. Best-corrected visual acuity was measured with the ETDRS chart. Three- and 6-month data were analyzed for all eyes. Results: Mean visual acuity improvement in the primary bevacizumab treatment cohort was 1.5 ETDRS lines at 3 months (P = 0.0009) and 2.2 ETDRS lines at 6 months (P = 0.0004) compared with -0.4 ETDRS line at 3 months (P = 0.27) and 0.2 ETDRS line at 6 months (P = 0.70) in the secondary bevacizumab treatment group. Mean decrease in retinal thickness was also higher in the primary bevacizumab treatment group (90.9 &mgr;m [P = 0.0037] vs 43.8 &mgr;m [P = 0.13], respectively) than in the secondary bevacizumab treatment group (73.72 &mgr;m [P = 0.051] vs 33.0 &mgr;m [P = 0.21], respectively) at 3 months and 6 months. Conclusion: Primary bevacizumab therapy resulted in significantly greater visual improvement than secondary bevacizumab treatment at 3 months or 6 months. To our knowledge, this is the first report comparing primary bevacizumab treatment of CNV in AMD with secondary bevacizumab treatment after multiple pegaptanib injections.

Multifocal electroretinography in HIV-positive patients without infectious retinitis.

PURPOSE To evaluate early changes in the central retinal response in human immunodeficiency virus (HIV)-positive patients without infectious retinitis using multifocal electroretinography (mfERG). DESIGN Case control study. METHODS We evaluated three cohorts: HIV-negative controls and two groups of HIV-positive patients separated according to their nadir CD4 counts (>or= 100 cells/mm(3) and < 100 cells/mm(3) for a minimum of six months). mfERG first-order kernels (FOKs) and second-order kernels (SOKs) were analyzed separately by areas of rings, quadrants, and individual hexagons for each cohort. RESULTS Of 103 hexagon locations of FOK results, there were no significant differences in amplitudes of P1 and N1 across the groups (.05 < P < .50), although there was a trend for an overall reduction in the amplitudes. Similarly, latency N1 did not differ (.28 < P < .95). There were significantly delayed latencies of P1 between cohorts across 103 hexagons in both kernels. SOK results also showed significant delay in latencies of P1 and a trend of reduced P1 amplitudes across studied locations among cohorts (.24 < P < .08). CONCLUSIONS The results demonstrate widespread delay in latency in HIV-positive patients, especially in those with prolonged low (below 100 cells/mm(3)) CD4 nadir counts. These findings suggest early diffuse dysfunction of the inner retina results from severe HIV disease even in the HAART era.

Assessment of retinal function in patients with HIV without infectious retinitis by multifocal electroretinogram and automated perimetry.

Purpose: To determine if multifocal electroretinogram (mfERG) testing shows abnormalities that correspond to perimetric defects in HIV positive patients without infectious retinitis. Methods: We studied three groups of patients: HIV negative controls, HIV high CD4 nadir patients (lowest CD4 T cell count is over 100) and low CD4 nadir patients (below 100 for over 6 months). Twenty-six HIV positive eyes and 16 HIV negative control eyes were studied by mfERG. A subset of 10 eyes also underwent computerized perimetry for comparison. We analyzed mfERG by hexagons as well as by quadrants and rings. Results: Of 103 hexagon locations there was no significant difference in the amplitudes P1 and N1 (nV/degree2) between the three studied groups (p>0.05), similarly, the latencies were not different (p>0.05). All eyes with significant visual field defects at the 0.01 and 0.005 level (Humphrey pattern deviation; 24-2) were compared to mfERG amplitudes and latencies at those locations–there were no corresponding defects in mfERG data (p>0.2). Conclusion: In the era of HAART there are still demonstrable visual field defects and other evidence of damage to the retinal nerve fiber layer in HIV patients. Our mfERG studies show that the damage appears to affect the inner retina, the outer retina is spared. Further studies of inner retinal structure and function are indicated to elucidate this process.

Comparison of 4 mg versus 20 mg intravitreal triamcinolone acetonide injections

Aims: To compare the non-decanted (standard) 4 mg versus the decanted 20 mg intravitreal triamcinolone acetonide (IVTA) injections and to assess their effect on intraocular pressure (IOP). Methods: We retrospectively reviewed the records of 92 consecutive eyes, which received an intravitreal injection of either dose of triamcinolone acetonide, at a single retina centre. The change in IOP (elevation of at least 5 mm Hg from baseline or above 21 mm Hg) was analysed with a multivariate logistic analysis. The mean follow-up period in both groups was 27 weeks. A subgroup analysis comparing vitrectomised to non-vitrectomised eyes in both groups was also performed. Results: Of the 92 eyes, 46% (23 of 51) in the 4 mg group versus 30% (12 of 41) in the 20 mg group had an IOP >21 mm of Hg (p = 0.14) after a mean follow-up period of 27 weeks. The vitrectomised eyes (3 of 24) in the 20 mg group had a significantly lower rate of IVTA induced IOP elevation than the non-vitrectomised eyes (9 of 17) (p = 0.013). The IOP elevation occurred significantly earlier in the 4 mg group (vitrectomised eyes 27 (SD 43) days and non-vitrectomised eyes 61 (52) days) than in the 20 mg group (vitrectomised eyes 104 (56) days and non-vitrectomised eyes 119 (82) days), independent of the vitreous status (vitrectomised p = 0.05 and non-vitrectomised p = 0.04). The mean value of initial high IOP in the non-vitrectomised eyes was higher in the 4 mg group than in the corresponding 20 mg group (p = 0.048). Conclusion: Decanted 20 mg IVTA may not pose a significantly greater risk of IOP elevation than the 4 mg non-decanted IVTA.

Imaging vitreomacular interface abnormalities in the coronal plane by simultaneous combined scanning laser and optical coherence tomography

Aim: To describe vitreoretinal imaging of eyes with vitreomacular abnormalities using high-resolution coronal-plane optical coherence tomography (OCT) scanning combined with simultaneous scanning laser ophthalmoscope (SLO) imaging. Methods: A SLO–OCT (OTI, Canada) was used to scan 835 eyes in 736 patients with vitreomacular interface abnormalities including epiretinal membranes, macular hole, incomplete posterior vitreous detachment, vitreomacular traction syndromes and diabetic and cystoid macular oedema in a retrospective study. The longitudinal-B scan images and the transverse -C scan images in the coronal plane were used to describe vitreomacular interface abnormalities. The SLO–OCT simultaneously produces a confocal image of the retina. Results: The longitudinal “B” scan and en-face “C” scan images allowed identification of tractive forces of epiretinal membrane, contour of the hyaloid membrane and changes in inner retinal surface. A simultaneously obtained OCT scan and SLO image of the fundus offered exact co-localisation of retinal structures and vitreomacular interface abnormalities. Conclusion: Scanning the vitreomacular interface by using combined OCT and SLO enables the visualisation and better understanding of various vitreomacular interface abnormalities, due to the ability to colocalise pathology on OCT with retinal vascular landmarks and the ability to visualise pathology from a new perspective, coronal plane parallel to retinal surface.

Prefilled syringe needles versus standard removable needles for intravitreous injection.

Purpose: To investigate differences in the scleral resistance between standard disposable 27 gauge (G) needle versus the Macugen prefilled syringe needle. Methods: Observational study at one eye center. One injecting physician performed 46 intravitreous injections using standard Becton Dickinson 27 G needles and 71 intravitreous injections using Macugen needles during January to May 2005. The procedure in two patients was videotaped and analyzed frame by frame. Microphotographs of used needles were analyzed. Results: There were no complications during the injection procedure in either group. Microphotographic analysis after injection revealed 3 and 5 facets on standard 27 G needle and Macugen needles, respectively. The bevel forming the tip of the 27 G needle was steeper and longer than that of the Macugen needle. The inside diameter in the standard 27 G needle was 220 &mgr;m versus 210 &mgr;m in the Macugen needle. Conclusion: There are differences in needle design between commonly used disposable 27 G needles and 27 G Macugen needles which result in higher resistance to penetration with Macugen needle. Careful needle design is an important concern in manufacturing prefilled syringes with needles attached to them.

Intraocular Properties of a Repository Urokinase Receptor Antagonist Å36 Peptide in Rabbits

Purpose: To evaluate the intraocular properties of Å36, a peptide that directly antagonizes the cell surface urokinase receptor and so prevents pericellular urokinase plasminogen activator activity. Methods: A total of 41 rabbits were used. The toxicity study tested three doses of Å36: 1 mg/ eye, 0.3 mg/eye, and 0.1 mg/eye. At 2 and 12 weeks, eyes were evaluated by ERG and histology. Pharmacokinetics were studied in rabbit eyes with the dose of 1 mg/eye in two different formulations: a micronized preparation and a non-micronized formulation. Eyes were enucleated at months 1, 2, 3, 4, and 5. Vitreous, retina, and choroid were collected separately for active Å36 analysis. Results: We did not find ocular toxicity with low and medium doses. At the highest dose, there was a transient toxicity at 2 weeks but was not notable at 3 months. The target choroid concentration of Å36 was chosen as ≥100 nM. The micronized formulation at months 1, 2, and 3 combined, showed variable levels in the choroid giving 5/10 (50%) of the therapeutic level; the non-micronized formulation at months 4 and 5 combined, gave 6/7 (86%) of the therapeutic level, although this difference was not statistically significant. Conclusion: Å36 appears to be long lasting; the non-micronized formulation of Å36 gave concentrations above therapeutic level in the choroid at months 4 and 5. Optimization of the formulation of Å36, particularly the particle size, may result in a promising new compound for exudative age-related macular degeneration treatment.