Brian C. Stagg

Anterior chamber intraocular lens, sutured posterior chamber intraocular lens, or glued intraocular lens: where do we stand?

Purpose of review To review the recent literature addressing the surgical approaches to intraocular lens (IOL) fixation in the setting of inadequate capsular support. Recent findings Lack of capsular support is a commonly encountered problem facing the anterior segment surgeon. Recent reports suggest that visual outcomes are generally good with modern IOLs and surgical approaches. More recently described techniques include sutureless scleral fixation and intraocular endoscopy-guided suture placement. Summary Many clinical circumstances require extracapsular IOL fixation and multiple options exist in the setting of inadequate capsular support. Ultimately, there are many factors that must be considered in selecting an appropriate surgical approach. These include ocular history as well as the skill, experience, and comfort level of the individual surgeon. The myriad of options that now exist for IOL fixation increases the likelihood that patients with a wide variety of pathologic states will attain their best possible visual outcome.

Targeted intraceptor nanoparticle therapy reduces angiogenesis and fibrosis in primate and murine macular degeneration

Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.

Promotion of Wellness and Mental Health Awareness Among Physicians in Training: Perspective of a National, Multispecialty Panel of Residents and Fellows

BACKGROUND Physicians in training are at high risk for depression, and physicians in practice have a substantially elevated risk of suicide compared to the general population. The graduate medical education community is currently mobilizing efforts to improve resident wellness. OBJECTIVE We sought to provide a trainee perspective on current resources to support resident wellness and resources that need to be developed to ensure an optimal learning environment. METHODS The ACGME Council of Review Committee Residents, a 29-member multispecialty group of residents and fellows, conducted an appreciative inquiry exercise to (1) identify existing resources to address resident wellness; (2) envision the ideal learning environment to promote wellness; and (3) determine how the existing infrastructure could be modified to approach the ideal. The information was aggregated to identify consensus themes from group discussion. RESULTS National policy on resident wellness should (1) increase awareness of the stress of residency and destigmatize depression in trainees; (2) develop systems to identify and treat depression in trainees in a confidential way to reduce barriers to accessing help; (3) enhance mentoring by senior peers and faculty; (4) promote a supportive culture; and (5) encourage additional study of the problem to deepen our understanding of the issue. CONCLUSIONS A multispecialty, national panel of trainees identified actionable goals to broaden efforts in programs and sponsoring institutions to promote resident wellness and mental health awareness. Engagement of all stakeholders within the graduate medical education community will be critical to developing a comprehensive solution to this important issue.

Nanoparticle-Mediated Delivery of shRNA.VEGF-A Plasmids Regresses Corneal Neovascularization

PURPOSE To determine the efficacy of a plasmid containing a small hairpin RNA expression cassette (pSEC.shRNA) against VEGF-A-loaded poly(lactic co-glycolic acid) nanoparticles (PLGA NPs) in the sustained regression of murine corneal neovascularization. METHODS PLGA nanoparticles were loaded with pSEC.shRNA.VEGF-A plasmids using the double emulsion-solvent evaporation method. KNV was induced in BALB/c mice by mechanical-alkali injury. Four weeks after induction of KNV, the mice were randomly divided to receive one of four treatments intrastromally: pSEC.shRNA.VEGF-A PLGA NPs (2 μg plasmid); naked pSEC.shRNA.VEGF-A plasmid only (2 μg plasmid); control blank PLGA NPs (equivalent dry weight of NPs); and vehicle. Two and five days after intervention, corneas were harvested to determine VEGF-A gene and protein expression using reverse transcriptase polymerase chain reaction and ELISA, respectively. Four weeks after intervention, corneas were photographed, mice sacrificed, and the corneal whole mounts were immunostained for CD31 (panendothelial cell marker). Immunofluorescence microscopy was performed and the neovascular area was quantitated. RESULTS VEGF-A mRNA (49.6 ± 12.4 vs. 82.9 ± 6.0%, P < 0.01) and protein (4.0 ± 5.2 vs. 20.0 ± 7.5 ρg VEGF-A/mg total protein, P < 0.05) expression were significantly reduced in pSEC.shRNA.VEGF-A PLGA NP-treated corneas as compared with control blank NP. The pSEC.shRNA.VEGF-A PLGA NP-treated corneas showed significant regression in the mean fractional areas of KNV (0.125 ± 0.042; 12.5%, P <0.01) compared with both naked plasmid only (0.283 ± 0.004; 28.3%) and control (blank NPs = 0.555 ± 0.072, 55.5%) at 4 weeks post-treatment. CONCLUSIONS The pSEC.shRNA.VEGF-A-loaded PLGA NPs are an effective, nonviral, nontoxic, and sustainable form of gene therapy for the regression of murine KNV.

Optimum on-time duty cycle for micropulse technology

Purpose To evaluate the optimum on time for the most efficient removal of lens fragments using micropulsed ultrasound (US). Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Twenty porcine lens nuclei were soaked in formalin for 2 hours and then divided into 2.0 mm cubes. Using an US machine with a 0.9 mm bent and a 30‐degree bevel tip, the on time was varied every millisecond (ms) from 2 ms to 10 ms with the off time kept constant at 10 ms. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. Results The most efficient phacoemulsification was achieved with an on time of 6 ms. On times shorter than 6 ms were significantly less efficient (R2 = .82, P=.04). Greater on times did not result in a significant difference in efficiency (R2 = .03, P=.78) but did appear to have more chatter events when comparing 9 to 10 ms with 2 to 8 ms (P<.0001). Conclusions With micropulsed longitudinal US, a 6 ms on time was equally as efficient as longer on times, while shorter on times (2 to 5 ms) had decreased efficiency. At 9 ms and 10 ms on time, significantly more chatter was noted. Therefore, to maximize phacoemulsification, an on‐time setting of 6 ms is recommended. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Determining optimal ultrasound off time with micropulse longitudinal phacoemulsification

Purpose To evaluate the optimum off time for the most efficient removal of lens fragments using micropulse ultrasound (US). Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Porcine lens nuclei were soaked in formalin for 2 hours and then cut into 2.0 mm cubes using the Signature US machine with a bent 0.9 mm phaco tip with a 30‐degree bevel. The on time was 7 milliseconds (ms), and the off time was varied from 2 to 20 ms in 2 ms steps. Phacoemulsification efficiency (time for fragment removal) and chatter (number of times the fragment bounced from the tip) were measured. Results A nonsignificant linear increase in efficiency was observed with 2 to 6 ms of off time (R2 = .87, P = .24). A significant linear decrease in efficiency was observed with 6 to 20 ms (R2 = .74, P = .006). Conclusions With micropulse longitudinal US, 6 to 7 ms of off time was as efficient as shorter off times; longer off times (8 to 20 ms) showed decreased efficiency. Chatter was minimal and statistically similar throughout. To maximize phacoemulsification US efficiency, an off‐time setting of 6 ms is recommended. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Phacoemulsification efficiency with a radiused phaco tip

Purpose To evaluate radiused and nonradiused phacoemulsification tips to determine which tip is more efficient in removal of lens fragments using 3 ultrasound (US) modalities. Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Porcine lens nuclei were formalin‐soaked for 2 hours or 3 hours and then divided into 2.0 mm cubes. Thirty‐degree, 0.9 mm beveled radiused tips and nonradiused tips were used with torsional, transverse, and micropulsed US modalities. Bent tips were used with torsional and transversal US, and straight tips were used with micropulsed US. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. Results The mean phacoemulsification efficiency was statistically significantly decreased (increased time for removal) with the radiused tip compared with the nonradiused tip for torsional US only (2‐hour soaked lenses: 2.14 seconds ± 1.94 [SD] versus 1.18 ± 0.69 seconds [P < .05]; 3‐hour soaked lenses: 5.07 ± 4.2 seconds versus 2.52 ± 1.99 seconds [P < .05]). There was no difference in chatter results. Conclusion The radiused tip showed decreased efficiency with torsional US only. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Effect of phaco tip diameter on efficiency and chatter.

Purpose To evaluate 3 phacoemulsification tips of different sizes and determine which size is most efficient in lens fragment removal using 3 ultrasound (US) approaches. Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Porcine lens nuclei were formalin‐soaked for 2 hours then divided into 2.0 mm cubes; 1.1 mm, 0.9 mm, and 0.7 mm phaco tips were used with torsional and micropulsed US. The 1.1 mm tips were unavailable for torsional US, so 0.9 mm and 0.7 mm tips were used. Efficiency (amount of time for lens removal) and chatter (number of lens‐fragment repulsions from the tip) were determined. Results The mean phacoemulsification efficiency was highest with the 0.9 mm tip for all US variations. There were statistically significant differences between the 0.9 mm and 0.7 mm tips with micropulsed US (0.8 seconds ± 0.29 [SD] versus 1.4 ± 0.93 seconds; P=.0112) and transversal US (0.8 ± 0.17 seconds versus 1.4 ± 0.89 seconds; P=.0065). There was no significant difference between 0.9 mm and 0.7 mm tips with torsional US or between the 1.1 mm and 0.9 mm tips with micropulsed or transversal US; however, trends were identical, with 0.9 mm tips performing better than 0.7 mm and 1.1 mm tips. Conclusion With all 3 systems, the 0.9 mm tip was most efficient, with the fewest outliers and smallest standard deviation. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Determining Optimal Torsional Ultrasound Power for Cataract Surgery With Automatic Longitudinal Pulses at Maximum Vacuum Ex Vivo

PURPOSE To determine the optimal longitudinal power settings for Infiniti OZil Intelligent Phaco (IP) at varying torsional amplitude settings; and to test the hypothesis that increasing longitudinal power is more important at lower torsional amplitudes to achieve efficient phacoemulsification. DESIGN Laboratory investigation. METHODS setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. procedure: Individual porcine nuclei were fixed in formalin, then cut into 2.0 mm cubes. Lens cube phacoemulsification was done using OZil IP at 60%, 80%, and 100% torsional amplitude with 0%, 10%, 20%, 30%, 50%, 75%, or 100% longitudinal power. All experiments were done using a 20 gauge 0.9 mm bent reverse bevel phaco tip at constant vacuum (550 mm Hg), aspiration rate (40 mL/min), and bottle height (50 cm). main outcome measure: Complete lens particle phacoemulsification (efficiency). RESULTS Linear regression analysis showed a significant increase in efficiency with increasing longitudinal power at 60% torsional amplitude (R(2) = 0.7269, P = .01) and 80% torsional amplitude (R(2) = 0.6995, P = .02) but not at 100% amplitude (R(2) = 0.3053, P = .2). Baseline comparison of 60% or 80% vs 100% torsional amplitude without longitudinal power showed increased efficiency at 100% (P = .0004). Increasing longitudinal power to 20% abolished the efficiency difference between 80% vs 100% amplitudes. In contrast, 75% longitudinal power abolished the efficiency difference between 60% vs 100% torsional amplitudes. CONCLUSIONS Results suggest that longitudinal power becomes more critical at increasing phacoemulsification efficiencies at torsional amplitudes less than 100%. Increasing longitudinal power does not further increase efficiency at maximal torsional amplitudes.

The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration

PURPOSE To evaluate serum soluble Flt-1 (sFlt-1) in age-related macular degeneration (AMD) patients. DESIGN Case-control study. METHODS Study involved 56 non-AMD participants, 53 early AMD patients, and 97 neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS. RESULTS Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8 ± 2.9 pg/mL (± standard error of the mean), 88.2 ± 2.6 pg/mL, and 79.9 ± 2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, P < .01). For each 10-point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decrease by 27.8%, odds ratio (OR) = 0.722 (95% confidence interval [CI]: 0.588-0.888, P = .002) and 27.0%, OR = 0.730 (95% CI: 0.594-0.898, P = .003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD. CONCLUSIONS Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD.