Triamcinolone acetonide preparations: impact of crystal size on in vitro behavior.

PURPOSE: To characterize the in vitro behavior of three preparations of triamcinolone acetonide (TA). METHODS: Three preparations of TA were mixed with Balanced Salt Solution Plus: commercially available TA (Kenalog 40, Bristol-Myers Squibb, Princeton, NJ), compounded preservative-free triamcinolone acetonide (PFTA, New England Compounding Center, Framingham, MA), and triamcinolone acetonide injectable suspension (TAIS, TRIESENCE, Alcon, Inc., Fort Worth, TX). We determined the mean number of crystalline aggregates per high-power deconvolution microscopy field, largest aggregate area, and spectroscopic photometric absorption. RESULTS: Preservative-free triamcinolone acetonide had larger mean number of aggregates compared with TA (time 0 P = 0.002, 10 minutes P < 0.001) and TAIS (time 0 P < 0.001, 10 minutes P = 0.003). Aggregate size varied at both 0 and 10 minutes: TAIS > TA > PFTA. Spectroscopic photometric absorption decreased in direct correlation to aggregate size over time for all three preparations. CONCLUSION: In vitro, PFTA in Balanced Salt Solution Plus had more aggregates of smaller size than either TA or TAIS. By contrast, TAIS had much larger aggregate size than both PFTA and TA, and this increased over time. These findings correlate with the clinical observations that PFTA and TA tend to disperse throughout the vitreous, whereas TAIS tends to conglomerate and gravitate toward the most dependent portion of the eye in a globular fashion.

Lateral interactions: size does matter.

Usually a high-contrast, co-local mask increases contrast threshold (inhibition). Interestingly, a laterally displaced mask (flanker) can facilitate contrast detection (Vision Research 33 (1993) 993; 34 (1994) 73). When spatial scaling of these flanker effects was implied, stimulus bandwidth was confounded with spatial frequency (lambda(-1)). Under conditions where at lower spatial frequencies, the size (standard deviation, sigma) of the Gabor patch was smaller (sigma

Contour integration in peripheral vision reduces gradually with eccentricity.

Hess and Dakin reported that normally-sighted subjects using peripheral vision (beyond 10 degrees ) were unable to detect paths of alternating-phase Gabors embedded within randomly positioned Gabors, but could detect same-phase paths. This result led them to propose a "fundamental difference" between central and peripheral visual processing. While we were able to replicate many of their results, our normally-sighted observers could detect alternating-phase paths beyond 10 degrees. We found that path detection decreased monotonically as a function of eccentricity (0 degrees -30 degrees ) for both alternating-phase and same-phase stimuli. As with most visual functions the more difficult path detection condition (alternating-phase) declined slightly faster. The results for the normally-sighted observers could not be explained by poor fixation. Three people with substantial central vision loss (i.e. they can only use peripheral vision) could see both same- and alternating-phase stimuli with eccentric viewing of 13 degrees -17 degrees. Therefore central and peripheral vision appear to use similar visual mechanisms to perform the task, there being no fundamental difference.

Multiple myeloma recurrence with optic nerve infiltration diagnosed by vitrectomy, immunohistochemistry, and in situ hybridization.

PURPOSE: We present a case of multiple myeloma recurrence diagnosed by optic nerve infiltration. METHODS: Interventional case report with clinical, surgical, immunohistochemical, and fluorescence in situ hybridization correlation. RESULTS: A 51-year-old woman with a history of bilateral invasive ductal breast carcinoma and multiple myeloma, both in remission on maintenance bortezomib, was referred for sudden, painless loss of vision OS. Examination demonstrated anterior vitritis with severe optic disc elevation, with yellow-white thickening, peripapillary hemorrhages, and a retinal detachment inferiorly. Diagnostic vitrectomy showed CD138-positive and BRST2-negative cells. Fluorescence in situ hybridization was positive for del(13q) and p53 deletion and negative for CCND1/IGH. CONCLUSIONS: This is the first report of optic nerve infiltration of multiple myeloma as evidence of recurrence while on maintenance chemotherapy. We demonstrate that diagnostic vitrectomy and immunohistochemistry of vitreous fluid is feasible for the diagnosis of recurrent multiple myeloma.

The effect of biomicroscope illumination system on grading anterior chamber inflammation.

PURPOSE: To determine how a biomicroscope illumination system affects the grading of anterior chamber (AC) inflammation. DESIGN: Laboratory investigation. METHODS: An artificial AC was designed to replicate optically a human AC and was filled with 5-mum polystyrene beads suspended in ethanol. A high-definition video eyepiece camera recorded the moving beads. Using image processing software, the main outcomes measures determined were the average number of beads in a 1 x 1-mm field at varying widths of the slit-beam. RESULTS: The volume of light and number of beads observed increased significantly as the slit-beam widened. Additionally, 3 separate biomicroscopes of identical make and model were found to produce different levels of luminance at the same aperture dial settings, influencing the number of beads observed, with the brighter biomicroscope yielding higher bead counts. CONCLUSIONS: Ability to count beads and perhaps the ability to count inflammatory cells in an inflamed eye depend on a number of factors, including the level of illumination and width of the slit-beam. This study demonstrated that the brighter the illumination and the wider the beam, the more beads were observed. This illustrates the importance of standardizing biomicroscopy, particularly where consecutive observations are used to make clinical decisions and in cases of multicenter clinical trials where clinical data are evaluated across different facilities.

Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits.

PURPOSE: To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS: Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzyme-linked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS: After intravitreal injection in the treated eye, the mean maximum concentrations (C(max)) of bevacizumab in the iris/ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the C(max) was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the C(max) was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS: Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

Circulating anti-retinal antibodies as immune markers in age-related macular degeneration.

Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age-matched controls to detect circulating anti-retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age-matched control subjects (n = 39). The sera were analysed for anti-retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93.75%) and CNV (82.27%) were found to have a significantly (P = 0.02) higher titre of autoantibodies to the retina in comparison with controls (8.69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0.0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti-retinal immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD.