NONINFECTIOUS VITRITIS AFTER INTRAVITREAL INJECTION OF ANTI-VEGF AGENTS: Variations in Rates and Presentation by Medication.

PURPOSE: The purpose of this study was to describe and compare the rates and characteristics of noninfectious vitritis after intravitreal injection of bevacizumab (Avastin, Genentech, South San Francisco, CA), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron, Tarrytown, NY). METHODS: A retrospective case series evaluated intravitreal injections from 2006 to 2013. Cases of inflammatory response were separated into culture-positive endophthalmitis, noninfectious vitritis (not treated with intravitreal antibiotics), and indeterminate. Noninfectious cases were analyzed for rate, presentation, and clinical course. RESULTS: A total of 66,356 bevacizumab, 26,161 ranibizumab, and 8071 aflibercept injections were screened. The rates of noninfectious vitritis were 0.10% (67 cases) for bevacizumab, 0.02% (6 cases) for ranibizumab, and 0.16% (13 cases) for aflibercept. The differences were statistically significant based on Chi-square analysis (P < 0.001). Mean differences in visual decline were not significant by Kruskal-Wallis analysis (P = 0.12), but the percentage of patients with any visual decline did vary by medication according to Fisher exact test (P < 0.05). The percentage of patients with complaints of pain, blurred vision, and subjective floaters was not significantly different by medication based on Fisher exact testing (P = 0.2, P = 0.18, P = 0.16, respectively). Bevacizumab and aflibercept cases tended to present in separate chronological clusters. CONCLUSION: The results suggest a difference in rates of noninfectious vitritis for antivascular endothelial growth factor medications. Many cases tended to cluster instead of occurring at a consistent rate each year.

Characterization of sterile intraocular inflammatory responses after intravitreal bevacizumab injection.

PURPOSE: The purpose of this study was to determine the frequency and characteristics of sterile intraocular inflammation occurring after intravitreal bevacizumab (IVB) (Avastin, Genentech, South San Francisco, CA) injection and to analyze whether a repeat IVB or intravitreal ranibizumab (IVR) (Lucentis, Genentech) injection after an episode of postinjection inflammation elicits a repeat inflammatory reaction. METHODS: A retrospective case series evaluated 16,166 IVB injections administered between 2006 and 2008. Patients with postinjection inflammation were analyzed for the number of previous injections, time from prior injection to incident injection, presenting signs and symptoms, treatment, visual acuity, time from onset to resolution and recovery of vision, and whether repeat injection caused recurrent inflammation. RESULTS: The incidence of sterile intraocular inflammation after IVB injection resolving with topical antibiotics and steroids alone was 0.27% (44 of 16,166). The average number of prior IVB injections in the ipsilateral eye was 2.8 ± 0.4 with 10 cases occurring with first-time injections. The average time from injection to recovery of visual acuity was 53 ± 18 days, and from injection to resolution of inflammation was 37 ± 5 days. Thirty-six cases received subsequent IVB or intravitreal ranibizumab, and there were three episodes of recurrent inflammation with repeat IVB. The average follow-up was 17 ± 1 month. CONCLUSION: In most cases of sterile intraocular inflammation after IVB, visual acuity returned to baseline, and intraocular inflammation rarely recurred with repeat IVB or intravitreal ranibizumab.

Macular atrophy in birdshot retinochoroidopathy: an optical coherence tomography and multifocal electroretinography analysis.

PURPOSE: The purpose of this study was to evaluate macular atrophy by frequency-domain optical coherence tomography (OCT) in patients with birdshot retinochoroidopathy and to compare the resulting thickness measures with visual acuity and multifocal electroretinography (mfERG). METHODS: Measures were obtained from 14 eyes of 7 patients with birdshot retinochoroidopathy and 23 normal eyes. Optical coherence tomography-3 measures of macular thinning were related to visual acuity, mfERG response density, and time since diagnosis. Horizontal midline frequency-domain OCT scans identified which layers of the retina were primarily responsible for macular thinning. RESULTS: All eyes with a history of birdshot retinochoroidopathy for >10 years had abnormal mfERG response densities. Compared with those without anatomic thinning (n = 8), eyes with anatomic thinning (n = 6) had significantly lower visual acuity (P = 0.0006), foveal response density (P = 0.006), and overall mfERG response density (P = 0.009). Segmentation of retinal layers on frequency-domain OCT scans showed that anatomic thinning was as a result of reduction in the receptor 1 layer (REC+), the thickness of the segment extending from the proximal border of the outer plexiform layer to the Bruch membrane-choroid interface. CONCLUSION: Macular atrophy, as reflected in OCT evidence of macular thinning and mfERG evidence of macular function, occurs in patients with long-standing birdshot retinochoroidopathy. Measures of retinal layer thicknesses by frequency-domain OCT suggest that the atrophy occurs primarily in the outer retina.

Evolving trends in primary retinal detachment repair: microincisional vitrectomy and the role of OCT.

Retinal detachment repair continues to evolve toward less invasive techniques that can safely, efficiently, and consistently provide optimal outcomes. In fact, 53% of U.S. respondents to the American Society of Retinal Specialists 2013 Preferences and Trends Survey said they would perform a vitrectomy without scleral buckle to treat a retinal detachment with a superior tear, while 25% would perform pneumatic retinopexy, and 21% would use a scleral buckle with or without vitrectomy.11 Compared to in 2005, many more surgeons prefer vitrectomy-only repair, whereas fewer prefer scleral buckle. Interestingly, preferences toward pneumatic retinopexy have slightly declined, which may reflect increased confidence in vitrectomy surgery to repair a detached retina safely and efficiently as an alternative. Even complex detachments can be treated in a minimally invasive fashion with the improvements in instrumentation, trocars, and oil infusion. While trends will likely continue toward minimal invasiveness, some form of scleral buckle, vitrectomy, and pneumatic retinopexy will all persist as treatment options. OCT advancements may allow for individualized discussions of visual prognosis and surgical decision making without the need for any invasive testing.

A prospective pilot study comparing combined intravitreal ranibizumab and half-fluence photodynamic therapy with ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration.

PURPOSE: This prospective multi-center pilot study compares the use of half-fluence photodynamic therapy combined with ranibizumab with ranibizumab monotherapy for the treatment of neovascular age-related macular degeneration. METHODS: All patients presenting with untreated subfoveal neovascular age-related macular degeneration were considered for inclusion. Patients were randomized to receive either ranibizumab with half-fluence photodynamic therapy or ranibizumab alone. Patients in the ranibizumab alone group were given three consecutive monthly ranibizumab injections and were followed monthly. They were treated with ranibizumab as needed, based on clinical discretion, using vision and optical coherence tomography. Patients in the combined group were given one same-day combined ranibizumab and half-fluence (25 j/cm(2)) photodynamic therapy treatment and were treated monthly as needed. Outcomes included changes in standardized visual acuity, optical coherence tomography foveal thickness, and percentage of as-needed injections to maintenance examinations. RESULTS: Fifty-six out of 60 enrolled patients completed the twelve month primary outcome visit; this consisted of 27 patients receiving ranibizumab alone and 29 receiving combined treatment. The average age was 79.1 for the ranibizumab alone group and 79.3 for the combined group. The mean visual acuity in the ranibizumab alone group improved from 52.9 Early Treatment of Diabetic Retinopathy letters initially to 62.8 letters at twelve months. The mean visual acuity in the combined group improved from 49.2 letters to 51.8 letters at twelve months. The differences in visual acuity improvements were not statistically significant based on a two-tailed t-test (P = 0.2). Due to the presence of outliers in each group, a Mann-Whitney U test was performed to confirm the results (U = 325; P = 0.28). The mean optical coherence tomography foveal thickness improved 92.5 microns and 106.7 microns in the ranibizumab alone and the combined group, respectively. The difference was not significant based on a two-tailed t-test (P = 0.6). The ranibizumab alone group received an average of 6.8 injections, while the combined group received an average of three injections. This difference was not significant based on a chi-square test (P = 0.11). CONCLUSION: The groups appeared similar based on statistical analysis, but larger studies are needed to determine possible small differences between combination therapy and monotherapy.

Characterization of water distribution in xanthan-curdlan hydrogel complex using magnetic resonance imaging, nuclear magnetic resonance relaxometry, rheology, and scanning electron microscopy.

UNLABELLED: Xanthan-curdlan hydrogel complex (XCHC) has been shown capable of retaining moisture up to 5 freeze-thaw cycles (FTCs); however, moisture distribution in the complex in relation to the hydrogel composition and structure remains uncharacterized. In the present study, magnetic resonance imaging (MRI), nuclear magnetic resonance (NMR) relaxometry, rheology, and scanning electron microscopy (SEM) were used to examine the effect of water distribution and interaction with 2.0% aqueous solutions of xanthan, curdlan, and XCHC consisting of equal amounts of both polysaccharides. A gel structure with an indication of syneresis was clearly seen in the MR image of curdlan alone, whereas the distribution of protons throughout xanthan and XCHC samples remained homogeneous and showed no detectable syneresis. The three-dimensional network, indicated by frequency sweeps, of curdlan was responsible for curdlan's gel structure. The frequency sweep and slope of the storage modulus (G') of XCHC was significantly closer to curdlan with higher elasticity and less dependency upon angular frequency than xanthan alone. The reduction in XCHC dynamic moduli (G' and G″) compared to curdlan could be attributed to the formation of wavy layers instead of a fully cured three-dimensional structure. Addition of xanthan to curdlan restricted XCHC spin-spin relaxation time (T2) to intermediate and slower exchange regimes, namely approximately 110 and 342 ms, respectively, promoting the polymer's interaction with water while inhibiting interpolymer interactions found in curdlan. A 3rd proton pool with the slowest T2 seen in curdlan was not found in XCHC, correlating to the absence of syneresis. PRACTICAL APPLICATION: The combination of texture measurements and discrete noninvasive techniques was found capable of providing insightful understanding of water distribution in a gel system. These techniques may be applied to other hydrogel complexes. The XCHC system investigated has the potential to enhance freeze-thaw stability in frozen food products by minimizing syneresis due to undesirable temperature fluctuations during distribution and consumer application.

Tobacco biomass hydrolysate enhances coenzyme Q10 production using photosynthetic Rhodospirillum rubrum.

Coenzyme Q10 (CoQ10), a potent antioxidative dietary supplement, was produced using a photosynthetic bacteria Rhodospirillum rubrum ATCC 25852 by submerged fermentation supplemented with tobacco biomass hydrolysate (TBH) in comparison with media supplemented with hydrolysates prepared with alfalfa (ABH) or spinach (SBH). Growth medium supplemented with 20% (v/v) TBH was found favorable with regard to cell density and CoQ10 concentration. The stimulation effects on cell growth (shortened lag phase, accelerated exponential growth, and elevated final cell concentration) and CoQ10 production (enhanced specific CoQ10 content per unit cell weight) could be attributed to the presence of solanesol, the precursor of CoQ10, in the tobacco biomass. The final yield of CoQ10 reached 20.16 mg/l in the fermentation medium supplemented with 20% TBH.

Vision loss associated with the use and removal of intraocular silicone oil.

PURPOSE: To describe vision loss associated with the use or removal of silicone oil retinal tamponade. METHODS: Records were reviewed of all patients with a decrease in visual acuity of at least 3 Snellen lines from best acuity with 5000 centistoke silicone oil in place or after removal of silicone oil at a single retina-only practice between 1996 and 2006. RESULTS: Nine patients (6 men, 3 women) with a mean age of 48 years (range, 16-61) met study inclusion criteria. Seven patients lost at least three Snellen lines of vision while the silicone oil was in place. Four patients had late modest improvements in acuity when compared to their final recorded Snellen vision before silicone oil removal, however no patients exhibited visual improvement when comparing their final recorded visual acuities after oil removal with best recorded acuities under oil tamponade. Loss of the foveal depression was a consistent feature on optical coherence tomography. CONCLUSIONS: Vision loss is a possible complication of silicone oil use and removal. Late visual improvement may occur in some patients. Further research is warranted to elucidate the mechanism(s) of vision loss associated with the use or removal of silicone oil.

Effects of Ultraviolet Radiation on the Gram-positive marine bacterium Microbacterium maritypicum.

Although extensive information is available on the effect ultraviolet (UV) radiation has on Gram-negative marine bacteria, there is a scarcity of data concerning UV radiation and Gram-positive marine bacteria. The focus of this paper is on Microbacterium maritypicum, with the Gram-negative Vibrio natriegens being used as a standard of comparison. M. maritypicum exhibited growth over a NaCl range of 0-1000 mM: , with optimum growth occurring between 0 and 400 mM: NaCl. In contrast, V. natriegens grew over a NaCl span of 250-1000 mM: , with best growth being observed between 250 and 600 mM: NaCl. UV radiation experiments were done using the medium with 250 mM: NaCl. For solar (UV-A and B) radiation and log-phase cells, M. maritypicum was determined to be three times more resistant than V. natriegens. For germicidal (UV-C) radiation, the pattern of resistance of the log-phase cells to the lethal effects of the radiation was even more pronounced, with the Gram-positive bacterium being more than 12 to 13 times more resistant. Similar data to the solar and germicidal log-phase UV kill curves were obtained for stationary-phase cells of both organisms. Photoreactivation was observed for both types of cells exposed to UV-C but none for cells treated with UV-A and B. When log phase cells of M.maritypicum were grown at 0.0 and 0.6 M: NaCl and exposed to UV-C radiation, no difference in survivorship patterns was noted from that of 0.25 M: NaCl grown cells. Although this study has only focused on two marine bacteria, our results indicate that the Gram-positive M. maritypicum could have a built-in advantage for survival in some marine ecosystems.

Periocular dog bite injuries and responsible care.

PURPOSE: To report patients who received dog bite injuries to the periocular area and the incidence of repeat attacks by the biting dog and its disposition. To discuss the demographics of bite attacks, occult injuries, steps to avoid medicolegal problems, and the appropriate options for animal disposition. METHODS: Single-practice prospective case series of dog attacks on 18 victims. Patients were followed and questioned about any repeat attacks by the offending dog. RESULTS: Of 18 individuals who received dog bites to the perio-ocular area, only 2 were >12 years old. Of the 16 cases available for follow-up (4 months to 3 years; mean, 16 months), 7 of the dogs were euthanized and 1 was sent away from the family. Of the 8 remaining animals, 5 (63%) bit again. All the dogs bit family members or family friends. CONCLUSIONS: Although most dogs make wonderful pets, canine bites pose a significant public health concern, and some simple steps may be taken to protect against personal injury and legal fallout from repeat attacks.