Topical drug delivery devices: A review

Aqueous Angiography in Living Nonhuman Primates Shows Segmental, Pulsatile, and Dynamic Angiographic Aqueous Humor Outflow.

Author(s): Neiweem, Ashley E; Bussel, Igor I; Schuman, Joel S; Brown, Eric N; Loewen, Nils A | Abstract: PurposeTo compare intraocular pressure (IOP) reduction and to develop a predictive surgery calculator based on the results between trabectome-mediated ab interno trabeculectomy in pseudophakic patients versus phacoemulsification combined with trabectome-mediated ab interno trabeculectomy in phakic patients.MethodsThis observational surgical cohort study analyzed pseudophakic patients who received trabectome-mediated ab interno trabeculectomy (AIT) or phacoemulsification combined with AIT (phaco-AIT). Follow up for less than 12 months or neovascular glaucoma led to exclusion. Missing data was imputed by generating 5 similar but non-identical datasets. Groups were matched using Coarsened Exact Matching based on age, gender, type of glaucoma, race, preoperative number of glaucoma medications and baseline intraocular pressure (IOP). Linear regression was used to examine the outcome measures consisting of IOP and medications.ResultsOf 949 cases, 587 were included consisting of 235 AIT and 352 phaco-AIT. Baseline IOP between groups was statistically significant (p≤0.01) in linear regression models and was minimized after Coarsened Exact Matching. An increment of 1 mmHg in baseline IOP was associated with a 0.73±0.03 mmHg IOP reduction. Phaco-AIT had an IOP reduction that was only 0.73±0.32 mmHg greater than that of AIT. The resulting calculator to determine IOP reduction consisted of the formula -13.54+0.73 × (phacoemulsification yes:1, no:0) + 0.73 × (baseline IOP) + 0.59 × (secondary open angle glaucoma yes:1, no:0) + 0.03 × (age) + 0.09 × (medications).ConclusionsThis predictive calculator for minimally invasive glaucoma surgery can assist clinical decision making. Only a small additional IOP reduction was observed when phacoemulsification was added to AIT. Patients with a higher baseline IOP had a greater IOP reduction.

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Glaucoma Surgery Calculator: Limited Additive Effect of Phacoemulsification on Intraocular Pressure in Ab Interno Trabeculectomy.

Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models.

A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork.

Recently introduced microincisional glaucoma surgeries that enhance conventional outflow offer a favorable risk profile over traditional surgeries, but can be unpredictable. Two paramount challenges are the lack of an adequate training model for angle surgeries and the absence of an intraoperative quantification of surgical success. To address both, we developed an ex vivo training system and a differential, quantitative canalography method that uses slope-adjusted fluorescence intensities of two different chromophores to avoid quenching. We assessed outflow enhancement by trabecular micro-bypass (TMB) implantation or by ab interno trabeculectomy (AIT). In this porcine model, TMB resulted in an insignificant (p > 0.05) outflow increase of 13 ± 5%, 14 ± 8%, 9 ± 3%, and 24 ± 9% in the inferonasal, superonasal, superotemporal, and inferotemporal quadrant, respectively. AIT caused a 100 ± 50% (p = 0.002), 75 ± 28% (p = 0.002), 19 ± 8%, and 40 ± 21% increase in those quadrants. The direct gonioscopy and tactile feedback provided a surgical experience that was very similar to that in human patients. Despite the more narrow and discontinuous circumferential drainage elements in the pig with potential for underperformance or partial stent obstruction, unequivocal patterns of focal outflow enhancement by TMB were seen in this training model. AIT achieved extensive access to outflow pathways beyond the surgical site itself.

/pdf/differential-canalograms-detect-outflow-changes-from-26v3kuq0db.pdf

Differential Canalograms Detect Outflow Changes from Trabecular Micro-Bypass Stents and Ab Interno Trabeculectomy

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.

Pritha Sengupta

Papers

Regionally Discrete Aqueous Humor Outflow Quantification using Fluorescein Canalograms