Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening.

AimTo analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG).MethodsProspective study of AIT and phaco-AIT with narrow angles of SG≤2 versus open angles ≥3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP <21 mm Hg and >20% reduction without further surgery). Exclusion criteria were missing preoperative data and <1 year follow-up.ResultsOf 671 included cases, at 1 year AIT SG≤2 (n=43) had an IOP reduction of 42% from 27.3±7.4 to 15.7±3.0 mm Hg (p<0.01) versus AIT SG≥3 (n=271) with an IOP reduction of 37% from 26.1±7.8 to 16.4±3.9 mm Hg (p<0.01). In phaco-AIT with SG≤2 (n=48), IOP was reduced 24% from 20.7±7.0 to 15.7±3.6 mm Hg (p<0.01) versus phaco-AIT with SG≥3 (n=309) with an IOP reduction of 25% from 22.6±6.4 to 17.0±3.4 mm Hg (p<0.01). There was no difference between SG≤2 and SG≥3 in reduction of IOP or medications, complications, secondary surgery and success rates (p>0.05).ConclusionsSG≤2 is not associated with worse outcomes in AIT or phaco-AIT

Impact of a glaucoma severity index on results of trabectome surgery: Larger pressure reduction in more severe glaucoma

Purpose: To stratify outcomes of trabectome-mediated ab interno trabeculectomy (AIT) by glaucoma severity using a simple and clinically useful glaucoma index. Based on prior data of trabectome after failed trabeculectomy, we hypothesized that more severe glaucoma might have a relatively more reduced facility compared to mild glaucoma and respond with a larger IOP reduction to trabecular meshwork ablation. Methods: Patients with primary open angle glaucoma who had undergone AIT without any other same session surgery and without any second eye surgery during the following 12 months were analyzed. Eyes of patients that had less than 12 months follow up or were diagnosed with neovascular glaucoma were excluded. A glaucoma index (GI) was created to capture glaucoma severity based on visual field, number of preoperative medications, and preoperative IOP. Visual field (VF) was separated into 3 categories: mild, moderate, and advanced (assigned 1,2, and 3 points, respectively). Preoperative number of medications (meds) was divided into 4 categories: ≤1, 2,3 or ≥4, and assigned with a value of 1 to 4. Baseline IOP (IOP) was divided into 3 categories: 12-18 (Group 3) and >18 (Group 4). Linear regression was used to determine if there was an association between GI group and IOP reduction after one year or age, gender, race, diagnosis, cup to disc (C/D) ratio, and Shaffer grade. Results: Out of 1340 patients, 843 were included in the analysis. The GI group distribution was GI1 = 164, GI2 = 202, GI3 = 260, and GI4 = 216. Mean IOP reduction after one year was 4.0±5.4, 6.4±5.8, 9.0±7.6,12.0±8.0 mmHg for GI groups 1 to 4, respectively. Linear regression showed that IOP reduction was associated with GI group after adjusting for age, gender, race, diagnosis, cup to disc ratio, and Shaffer grade. Each GI group increase of 1 was associated with incremental IOP reductions of 2.95±0.29 mmHg. Success rate at 12 months was 90%, 77%, 77%, and 71% for GI groups 1 to 4. The log-rank test suggested significant differences between GI groups. Conclusion: A simple glaucoma index, GI, was created to capture glaucoma severity and a relative resistance to treatment. A higher GI was associated with a larger IOP reduction in trabectome surgery. This indicates that there is a role for AIT beyond mild glaucoma and ocular hypertension

Regionally discrete aqueous humor outflow quantification using fluorescein canalograms

Purpose To visualize and quantify conventional outflow directly in its anatomic location. Methods We obtained fluorescein canalograms in six porcine whole eyes and six porcine anterior segment cultures. Eyes were perfused with a constant pressure of 15 mmHg using media containing 0.017 mg/ml fluorescein. Flow patterns were visualized using a stereo dissecting microscope equipped for fluorescent imaging. Images were captured every 30 seconds for 20 minutes for time lapse analysis. Anterior chamber cultures were imaged again on day three of culture. Canalograms were first analyzed for filling time per quadrant. We then wrote a program to automatically compute focal flow fits for each macropixel and to detect convergent perilimbal flow patterns with macropixels grouped into 3 equal-radial width rings around the cornea. A generalized additive model was used to determine fluorescence changes of individual macropixels. Results The resulting imaging algorithm deployed 1024 macropixels that were fit to determine maximum intensity and time to fill. These individual fits highlighted the focal flow function. In whole eyes, significantly faster flow was seen in the inferonasal (IN) and superonasal (SN) quadrants compared to the superotemporal (ST) and inferotemporal (IT) ones (p<0.05). In anterior chamber cultures, reduced flow on day 1 increased in all quadrants on day 3 except in IT (p<0.05). Perilimbal ring analysis uncovered convergent perilimbal flow. Conclusions An algorithm was developed that analyzes regional and circumferential outflow patterns. This algorithm found flow patterns that changed over time and differ in whole eyes and anterior segment cultures

Longer-term Baerveldt to Trabectome glaucoma surgery comparison using propensity score matching

Purpose: To apply propensity score matching to compare Baerveldt glaucoma drainage implant (BGI) to Trabectome-mediated ab interno trabeculectomy (AIT). Recent data suggests that AIT can produce results similar to BGI which is traditionally reserved for more severe glaucoma. Methods: BGI and AIT patients with at least 1 year of follow-up were included. The primary outcome measures were intraocular pressure (IOP), number of glaucoma medications, and a Glaucoma Index (GI) score. GI reflected glaucoma severity based on visual field, the number of preoperative medications, and preoperative IOP. Score matching used a genetic algorithm consisting of age, gender, type of glaucoma, concurrent phacoemulsification, baseline number of medications, and baseline IOP. Patients with neovascular glaucoma, with prior glaucoma surgery, or without a close match were excluded. Results: Of 353 patients, 30 AIT patients were matched to 29 BGI patients. Baseline characteristics including, IOP, the number of glaucoma medications, type of glaucoma, the degree of VF loss and GI were not significantly different between AIT and BGI. BGI had a preoperative IOP of 21.6 ± 6.3 mmHg compared to 21.5 ± 7.4 for AIT on 2.8 ± 1.1 medications and 2.5 ± 2.3 respectively. At 30 months, the mean IOP was 15.0 ± 3.9 mmHg for AIT versus 15.0 ± 5.7 mmHg for BGI (p > 0.05), while the number of drops was 1.5 ± 1.3 for AIT (change: p = 0.001) versus 2.4 ± 1.2 for BGI (change: p = 0.17; AIT vs BGI: 0.007). Success, defined as IOP  0.05) and 50% versus 52% at 2.5 years. Conclusions: A propensity score matched comparison of AIT and BGI demonstrated a similar IOP reduction through 1 year. AIT required fewer medications

Coarsened exact matching of phaco-trabectome to trabectome in phakic patients: Lack of additional pressure reduction from phacoemulsification

Purpose To compare intraocular pressure (IOP) after trabectome-mediated ab interno trabeculectomy surgery in phakic patients (T) and trabectome with same session phacoemulsification (PT) using Coarsened Exact Matching. Although phacoemulsification is associated with IOP reduction when performed on its own, it is not known how much it contributes in PT. Methods Subjects were divided into phakic T and PT. Exclusion criteria were follow-up for <12 months and additional glaucoma surgery. Demographics were compared by the Mann- Whitney U test and chi-squared test for continuous and categorical variables, respectively. Multiple imputation was utilized to avoid eliminating data with missing values. Groups were then matched using Coarsened Exact Matching based on age, race, type of glaucoma, baseline IOP, and number of preoperative glaucoma medications. Univariate linear regression was used to examine IOP reduction after surgery; those variables that were statistically significant were included in the final multivariate regression model. Results A total of 753 cases were included (T: 255, PT: 498). When all variables except for age were kept constant, there was an additional IOP reduction of 0.05±0.01 mmHg conferred for every yearly increment in age. Every 1 mmHg increase in baseline IOP correlated to an additional IOP reduction of 0.80±0.02 mmHg. Phacoemulsification was not found to be a statistically significant contributor to IOP when comparing T and PT (p≥0.05). T had a 21% IOP reduction to 15.9±3.5 mmHg (p<0.01) while PT had an 18% reduction to 15.5±3.6 mmHg (p<0.01). Number of medications decreased (p<0.01) in both groups from 2.4±1.2 to 1.9±1.3 and from 2.3±1.1 to 1.7±1.3, respectively. Conclusion Phacoemulsification does not make a significant contribution to postoperative IOP or number of medications when combined with trabectome surgery in phakic patients

A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient

<p>Abstract</p> <p>Background</p> <p>We examined the therapeutic potential of a proprietary <it>Croton palanostigma </it>extract (Zangrado^®) in the management of emesis and itch.</p> <p>Methods</p> <p>Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the <it>Apc</it>^<it>Min</it>mouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.</p> <p>Results</p> <p>Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the <it>Apc</it>^<it>Min</it>condition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.</p> <p>Conclusion</p> <p>Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.</p

Cyclophilin A interacts with diverse lentiviral capsids

BACKGROUND: The capsid (CA) protein of HIV-1 binds with high affinity to the host protein cyclophilin A (CypA). This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity. The closely related lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact with CypA in a yeast two-hybrid assay. RESULTS: We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA. CONCLUSION: These results demonstrate that CypA binding to lentiviruses is more widespread than previously thought and suggest that this interaction is evolutionarily important for lentiviral infection

Outcomes of ab interno trabeculectomy with the trabectome after failed trabeculectomy.

AimTo evaluate outcomes of ab interno trabeculectomy (AIT) with the trabectome following failed trabeculectomy.MethodsProspective study of AITs and phaco-AITs after a failed trabeculectomy. The indication for AIT was intraocular pressure (IOP) above target on maximally tolerated therapy, and for phaco-AIT a visually significant cataract and need to lower IOP or glaucoma medications. Outcomes included IOP, medications, complications, secondary procedures and success, defined as IOP of less than 21 mm Hg and a greater than 20% reduction from baseline without further surgery. Exclusion criteria were trabeculectomy less than 3 months prior to AIT or follow-up under 1 year.ResultsSeventy-three eyes of 73 patients with 1 year follow-up were identified. At 1 year, mean IOP in AIT significantly decreased by 28% from 23.7±5.5 mm Hg, and medications from 2.8±1.2 to 2±1.3 (n=58). In phaco-AIT, the mean IOP decreased 19% from 20±5.9 mm Hg and medications from 2.5±1.5 to 1.6±1.4 (n=15). Transient hypotony occurred in 7%, and further surgery was necessary in 18%. For AIT and phaco-AIT, the 1-year cumulative probability of success was 81% and 87%, respectively.ConclusionsBoth AIT and phaco-AIT showed a reduction in IOP and medication use after 1 year, suggesting that AIT with or without cataract surgery is a safe and effective option following failed trabeculectomy

Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening.

AimTo analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG).MethodsProspective study of AIT and phaco-AIT with narrow angles of SG≤2 versus open angles ≥3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP &lt;21 mm Hg and &gt;20% reduction without further surgery). Exclusion criteria were missing preoperative data and &lt;1 year follow-up.ResultsOf 671 included cases, at 1 year AIT SG≤2 (n=43) had an IOP reduction of 42% from 27.3±7.4 to 15.7±3.0 mm Hg (p&lt;0.01) versus AIT SG≥3 (n=271) with an IOP reduction of 37% from 26.1±7.8 to 16.4±3.9 mm Hg (p&lt;0.01). In phaco-AIT with SG≤2 (n=48), IOP was reduced 24% from 20.7±7.0 to 15.7±3.6 mm Hg (p&lt;0.01) versus phaco-AIT with SG≥3 (n=309) with an IOP reduction of 25% from 22.6±6.4 to 17.0±3.4 mm Hg (p&lt;0.01). There was no difference between SG≤2 and SG≥3 in reduction of IOP or medications, complications, secondary surgery and success rates (p&gt;0.05).ConclusionsSG≤2 is not associated with worse outcomes in AIT or phaco-AIT