Leonard K. Seibold

Comparison of Retinal Nerve Fiber Layer Thickness in Normal Eyes Using Time-Domain and Spectral-Domain Optical Coherence Tomography

PURPOSE To compare retinal nerve fiber layer (RNFL) thickness measurements between 3 different spectral-domain optical coherence tomography (SD-OCT) instruments (Spectralis; Heidelberg Engineering; Cirrus; Carl Zeiss Meditec; RTVue; Optovue, Inc) and one time-domain OCT (Stratus; Carl Zeiss Meditec). DESIGN Prospective, cross-sectional study. METHODS RNFL thickness was measured on both eyes of 40 normal subjects using Stratus, Spectralis, RTVue, and Cirrus OCT on the same day. Scans were repeated 2 to 8 weeks later in the same fashion. Agreement with Stratus was evaluated for each SD-OCT and intervisit reproducibility was assessed for all machines. RESULTS Mean RNFL thickness determined by each of the 3 SD-OCT instruments was highly correlated with Stratus (r = 0.87-0.91). The mean RNFL thickness (mean ± standard deviation) was 110.1 ± 12.8 μm for Stratus, 106.6 ± 12.8 μm for Spectralis, 98.7 ± 10.9 μm for Cirrus, and 112.8 ± 13.2 μm for RTVue. The average differences between each SD-OCT and Stratus for mean RNFL thickness were all statistically significant (P ≤ .001), as were most quadrant measurements. All 4 instruments demonstrated excellent intraclass correlation coefficient values for mean RNFL thickness (0.90-0.97). However, intervisit variability was lowest for RTVue as evidenced by reproducibility values, followed by Stratus, Cirrus, and Spectralis (6.59, 8.83, 8.89, and 11.72 μm, respectively). CONCLUSIONS RNFL measurements taken with Spectralis, RTVue, and Cirrus all have excellent correlation to Stratus, with good reproducibility in normal eyes. Despite high correlations, RNFL values are significantly different between instruments and should not be used interchangeably.

Wound modulation after filtration surgery.

Filtration surgery is the standard invasive procedure for the management of intraocular pressure in advanced glaucoma. The key to a successful outcome is to modulate the normal wound healing cascade that leads to closure of the newly created aqueous outflow pathway. Antifibrotic agents such as mitomycin C and 5-fluorouracil have been increasingly used to modulate the wound healing process and increase surgical success. Although these agents have proven efficacy, they also increase the risk of complications. Efforts have centered on the identification of novel agents and techniques that can influence wound modulation without these complications. We detail new agents and methods under investigation to control wound healing after filtration surgery.

Preclinical Investigation of Ab Interno Trabeculectomy Using a Novel Dual-Blade Device

PURPOSE To evaluate the effects of a novel ab interno trabeculectomy device on human trabecular meshwork (TM). DESIGN Laboratory evaluation. METHODS The TM from human cadaveric corneal rim tissue was incised using 3 instruments: (1) novel dual-blade device; (2) microvitreoretinal (MVR) blade; and (3) Trabectome. Tissue samples underwent histologic processing and comparative analyses. Subsequently, human eye perfusion studies were performed to evaluate intraocular pressure (IOP)-lowering effects of each device. Main outcome measures were degree of TM removal by histology and IOP in a perfusion model. RESULTS The MVR blade exhibited minimal removal of TM and obvious injury to the adjacent sclera. The Trabectome removed a large portion of the central TM, but leaflets of residual tissue remained and thermal injury was noted in all samples. The dual-blade device achieved a more complete removal of TM without injury to surrounding tissues. All devices resulted in statistically significant lowering of IOP during perfusion model studies. MVR blade treatment across 170.0 ± 14.1 degrees of TM resulted in a decrease of IOP from 18.5 ± 1.9 mm Hg to 12.8 ± 2.2 mm Hg (P < .01). Trabectome treatment across 117.5 ± 12.6 degrees resulted in a decrease of IOP from 18.8 ± 1.7 mm Hg to 11.3 ± 1.0 mm Hg (P < .01). Dual-blade device treatment across 157.5 ± 26.3 degrees resulted in a decrease of IOP from 18.3 ± 3.0 mm Hg to 11.0 ± 2.2 mm Hg (P < .01). CONCLUSIONS The novel dual-blade device demonstrated a more complete removal of TM without residual TM leaflets or damage to surrounding tissues and significantly reduced IOP in a human eye perfusion model.

Minimally invasive glaucoma surgery: current implants and future innovations

Traditionally, invasive surgical management of glaucoma is recommended when medication and/or laser trabeculoplasty fail to control intraocular pressure (IOP). Filtering procedures, such as trabeculectomy and glaucoma drainage devices, are effective in lowering IOP, but they have significant associated adverse events and rates of failure. For these reasons, a new group of surgical procedures has emerged that seeks to decrease IOP with lower associated rates of complications. The acronym MIGS, usually described as minimally invasive glaucoma surgery, has been coined to describe this group of procedures. As new devices become available, MIGS procedures will help to fill the gap between conservative medical and laser therapy and invasive surgical treatment of glaucoma to offer patients an earlier and safer transition to surgical management of their disease. In this review, we define the characteristics of an ideal MIGS procedure and discuss implants currently in use or under investigation.

MRI of the Ex-PRESS stainless steel glaucoma drainage device

Aim To evaluate the magnetic properties of the Ex-PRESS stainless steel glaucoma drainage device during MRI. Design Experimental study. Methods The Ex-PRESS glaucoma drainage device (316L stainless steel) was examined for magnetic field interactions under standard 1.5, 3.0, and 4.7 T MRI scanning protocols. Testing included measurements of translational and rotational motion of the device induced by static magnetic fields. In addition, the change in the temperature of the device was measured to assess the presence of radiofrequency heating of the stainless steel device. Main outcome measures Degree of angular deflection, device displacement and rotation, and change in temperature. Results During induced torque testing, displacement did not occur under 1.5 and 3.0 T conditions, although a significant amount of displacement occurred in the 4.7 T environment. Increasing amounts of angular deflection were demonstrated at all three field strengths. We did not record significant temperature changes during brain MRI sequences at any of the three MRI strengths. Conclusions The Ex-PRESS glaucoma drainage device, manufactured from grade 316L stainless steel, does move in the presence of high magnetic fields. The clinical significance of this finding and translation to in vivo conditions are not currently known. Further studies are needed to better understand how patients might be affected by the magnetic properties of this device post implantation and how patients should be counselled in regards to safety of MRI in the early and late postoperative period.

Recent Advances in the Management of Neovascular Glaucoma

ABSTRACT The development of anti-vascular endothelial growth factor (VEGF) molecules has expanded the range of available treatment options for many ocular diseases, including neovascular glaucoma (NVG). A number of studies have explored the use of anti-VEGF agents as stand-alone or adjunctive treatment for NVG. Although no large, prospective, randomized trials have been performed to date, the growing body of knowledge suggests that anti-VEGF agents are effective at reversing iris and angle neovascularization and lowering intraocular pressure in patients with NVG. Response to a single injection is typically temporary; therefore, laser or incisional surgery is still necessary in most cases. Future research is needed to determine the optimal agent, dose, route of administration, and timing of treatment either as monotherapy or coupled with other medical and/or surgical interventions.

Tafluprost: a novel prostaglandin analog for treatment of glaucoma.

ObjectiveThe objective of this review is to evaluate the safety and efficacy of tafluprost, a fluoroprostaglandin receptor analog, for reduction of intraocular pressure in open angle glaucoma and ocular hypertension.MethodsA search of published literature was performed on the PubMed database using the search term “tafluprost.” The literature search identified 48 publications, including clinical and preclinical studies, from 2003 to 2011. From these ressults, articles available in the English language and in full text were selected and systematically reviewed by the authors.ResultsRecent studies have shown that tafluprost is an effective IOP-lowering medication. Evidence based medicine also reveals that tafluprost is safe and well-tolerated. Preservative-free tafluprost is as potent as the preserved formulation, but with fewer and milder ocular surface side effects.ConclusionSince its introduction in 2008, initial studies have demonstrated that preserved and preservative-free tafluprost formulations have proven efficacy and safety in the treatment of glaucoma and ocular hypertension. Larger studies with longer follow-up are needed to assess long-term safety, efficacy, and tolerability compared with other prostaglandin analogs used for treating glaucoma.

Acute Effects of Glaucoma Medications and Benzalkonium Chloride on Pre-adipocyte Proliferation and Adipocyte Cytotoxicity In Vitro

Purpose: To determine and compare the short-term, in vitro effect of prostaglandin analogues (PGAs), timolol, and benzalkonium chloride (BAK) on pre-adipocyte proliferation and adipocyte cytotoxicity. Methods: For the proliferation assay, human primary subcutaneous pre-adipocytes were incubated in the presence of either bimatoprost (0.015%, 0.03%, 0.06%) travoprost (0.002%, 0.004%, 0.008%), latanoprost (0.0025%, 0.005%, 0.010%), tafluprost (0.00075%, 0.0015%, 0.003%), timolol maleate (0.25%, 0.5%, 1.0%), BAK (0.005%, 0.010%, 0.015%, 0.020%, 0.040%), or control of BAK vehicle. After 72 h in culture, cell numbers were determined by fluorescent assay with CellTiter-Blue® reagent. For the cytotoxity assay, mature human adipocytes were cultured for 72 h with the same test compounds and controls. Cell numbers were again determined in the same manner through fluorescence. Results: In the proliferation assay, all four PGA medications failed to show a statistically significant difference from BAK vehicle alone (p = 0.065–0.751). Both timolol and BAK alone demonstrated near complete inhibition of pre-adipocyte proliferation at all concentrations tested (p < 0.01 for all). In the cytotoxicity assay, all four PGAs again exerted no significant effect when compared to control (p = 0.211–0.901). Timolol and BAK again displayed near complete toxicity of adipocytes at all concentrations (p < 0.01 for all). Conclusions: All four PGAs had similar and negligible short-term effects on pre-adipocyte proliferation and adipocyte toxicity in vitro. Timolol and BAK had profound cytotoxic effects on mature adipocytes and antiproliferative effects on pre-adipocytes in vitro. Further testing is needed to determine whether similar effects are present in vivo.

Ab interno trabeculectomy in the adult patient

Glaucoma is a potentially blinding disease that affects millions of people worldwide. The mainstay of treatment is lowering of intraocular pressure (IOP) through the use of medications, laser and/or incisional surgery. The trabecular meshwork (TM) is thought to be the site of significant resistance to aqueous outflow in open angle glaucoma. Theoretically, an incision through TM or TM removal should decrease this resistance and lead to a significant reduction in IOP. This approach, commonly referred to as goniotomy or trabeculotomy, has been validated in the pediatric population and has been associated with long-term IOP control. In adults, however, removal of TM tissue has been historically associated with more limited and short-lived success. More recent evidence, reveals that even adult patients may benefit significantly from removal of diseased TM tissue and can lead to a significant reduction in IOP that is long-lasting and safe. In this review, we discuss current evidence and techniques for ab interno trabeculectomy using various devices in the adult patient.

Ultrastructural Changes in Human Trabecular Meshwork Tissue after Laser Trabeculoplasty

Purpose. To compare morphologic changes in human trabecular meshwork (TM) after selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT). Design. Laboratory evaluation of ex vivo human eye TM after laser trabeculoplasty. Methods. Corneoscleral rims from human cadaver eyes were sectioned and treated with varying powers of either SLT or ALT. Specimens were examined using light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Results. TEM of SLT at all powers resulted in disrupted TM cells with cracked and extracellular pigment granules. SEM of SLT samples treated at high power revealed tissue destruction with scrolling of trabecular beams. SEM of ALT-treated tissue showed increasing destruction with exposure to higher power. The presence or absence of “champagne” bubbles during SLT did not alter the histologic findings. Conclusions. SLT-treated human TM revealed disruption of TM cells with cracked, extracellular pigment granules, particularly at higher treatment powers. Tissue scrolling was noted at very high SLT energy levels. ALT-treated tissue showed significant damage to both the superficial and deeper TM tissues in a dose-dependent fashion. Further studies are needed to guide titration of treatment power to maximize the IOP-lowering effect while minimizing both energy delivered and damage to target tissues.