Brian A. Francis

Aqueous Shunts in Glaucoma: A Report by the American Academy of Ophthalmology

OBJECTIVE To provide an evidence-based summary of commercially available aqueous shunts currently used in substantial numbers (Ahmed [New World Medical, Inc., Rancho Cucamonga, CA], Baerveldt [Advanced Medical Optics, Inc., Santa Ana, CA], Krupin [Eagle Vision, Inc, Memphis, TN], Molteno [Molteno Ophthalmic Ltd., Dunedin, New Zealand]) to control intraocular pressure (IOP) in various glaucomas. METHODS Seventeen previously published randomized trials, 1 prospective nonrandomized comparative trial, 1 retrospective case-control study, 2 comprehensive literature reviews, and published English language, noncomparative case series and case reports were reviewed and graded for methodologic quality. RESULTS Aqueous shunts are used primarily after failure of medical, laser, and conventional filtering surgery to treat glaucoma and have been successful in controlling IOP in a variety of glaucomas. The principal long-term complication of anterior chamber tubes is corneal endothelial failure. The most shunt-specific delayed complication is erosion of the tube through overlying conjunctiva. There is a low incidence of this occurring with all shunts currently available, and it occurs most frequently within a few millimeters of the corneoscleral junction after anterior chamber insertion. Erosion of the equatorial plate through the conjunctival surface occurs less frequently. Clinical failure of the various devices over time occurs at a rate of approximately 10% per year, which is approximately the same as the failure rate for trabeculectomy. CONCLUSIONS Based on level I evidence, aqueous shunts seem to have benefits (IOP control, duration of benefit) comparable with those of trabeculectomy in the management of complex glaucomas (phakic or pseudophakic eyes after prior failed trabeculectomies). Level I evidence indicates that there are no advantages to the adjunctive use of antifibrotic agents or systemic corticosteroids with currently available shunts. Too few high-quality direct comparisons of various available shunts have been published to assess the relative efficacy or complication rates of specific devices beyond the implication that larger-surface-area explants provide more enduring and better IOP control. Long-term follow-up and comparative studies are encouraged.

Novel Glaucoma Procedures: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the published literature and summarize clinically relevant information about novel, or emerging, surgical techniques for the treatment of open-angle glaucoma and to describe the devices and procedures in proper context of the appropriate patient population, theoretic effects, advantages, and disadvantages. DESIGN Devices and procedures that have US Food and Drug Administration clearance or are currently in phase III clinical trials in the United States are included: the Fugo blade (Medisurg Ltd., Norristown, PA), Ex-PRESS mini glaucoma shunt (Alcon, Inc., Hunenberg, Switzerland), SOLX Gold Shunt (SOLX Ltd., Boston, MA), excimer laser trabeculotomy (AIDA, Glautec AG, Nurnberg, Germany), canaloplasty (iScience Interventional Corp., Menlo Park, CA), trabeculotomy by internal approach (Trabectome, NeoMedix, Inc., Tustin, CA), and trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA). METHODS Literature searches of the PubMed and the Cochrane Library databases were conducted up to October 2009 with no date or language restrictions. MAIN OUTCOME MEASURES These searches retrieved 192 citations, of which 23 were deemed topically relevant and rated for quality of evidence by the panel methodologist. All studies but one, which was rated as level II evidence, were rated as level III evidence. RESULTS All of the devices studied showed a statistically significant reduction in intraocular pressure and, in some cases, glaucoma medication use. The success and failure definitions varied among studies, as did the calculated rates. Various types and rates of complications were reported depending on the surgical technique. On the basis of the review of the literature and mechanism of action, the authors also summarized theoretic advantages and disadvantages of each surgery. CONCLUSIONS The novel glaucoma surgeries studied all show some promise as alternative treatments to lower intraocular pressure in the treatment of open-angle glaucoma. It is not possible to conclude whether these novel procedures are superior, equal to, or inferior to surgery such as trabeculectomy or to one another. The studies provide the basis for future comparative or randomized trials of existing glaucoma surgical techniques and other novel procedures.

Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: Initial results

PURPOSE: To provide an update of the short‐term results of combined phacoemulsification and trabeculotomy by the internal approach with a follow‐up to 21 months. SETTING: Universities and private practices in the United States. METHODS: This prospective interventional case series comprised 304 consecutive eyes with open‐angle glaucoma and cataract having combined phacoemulsification and trabeculotomy with a Trabectome (NeoMedix Inc.). The Trabectome is designed to open a direct pathway for aqueous to flow from the anterior chamber into Schlemm canal collector channels. Under gonioscopic control, bipolar cautery was applied by a purpose‐designed footplate to ablate the trabecular meshwork and inner wall of Schlemm canal. The main outcome measures were intraocular pressure (IOP), glaucoma medication use, and complications. RESULTS: The mean IOP was 20.0 mm Hg ± 6.3 (SD) preoperatively, 14.8 ± 3.5 mm Hg at 6 months, and 15.5 ± 2.9 mm Hg at 1 year. There was a corresponding drop in glaucoma medications from 2.65 ± 1.13 at baseline to 1.76 ± 1.25 at 6 months and 1.44 ± 1.29 at 1 year. Subsequent secondary glaucoma procedures were performed in 9 patients. The only frequent complication, blood reflux in 239 patients (78.4%), resolved within a few days. CONCLUSIONS: Combined phacoemulsification and trabeculotomy by the internal approach using the Trabectome lowered IOP and medication use in the majority of patients. Complications were minimal and comparable to those in an earlier series of Trabectome‐only procedures.

Ab Interno Trabeculectomy: Development of a Novel Device (trabectome™) and Surgery for Open-angle Glaucoma

Purpose:To design an instrument to selectively remove trabecular meshwork and Schlemms canal inner wall (SCIW), and demonstrate its effectiveness by histologic analysis of treated cadaveric human tissue. Methods:The design parameters of the instrument were the ability to permanently remove a segment of trabecular meshwork and Schlemms canal inner wall without causing damage to surrounding tissue, and to allow use with standard anterior segment surgical techniques and equipment via an ab interno approach. Treatment was applied to 20 segments of human corneoscleral rims. The treated areas were examined using a confocal microscope and compared with matching areas in untreated controls and simulated goniotomy. Results:The resultant instrument system surgically removes the trabecular meshwork and Schlemms canal inner wall from an anterior chamber approach. It consists of a disposable surgical handpiece with irrigation, aspiration, and electrocautery to focally ablate the target tissues. The attached console includes a high-frequency (550 KHz) electrosurgical generator and irrigation/aspiration controlled by a foot pedal. Histologic examination of specimens treated with the Trabectome™ displayed disruption of the trabecular meshwork and Schlemms canal inner wall without damage to surrounding structures. The specimens treated by simulated goniotomy displayed significant damage to the outer wall of Schlemms canal and the surrounding sclera. The controls showed no disruption or damage to any tissues. Conclusions:The Trabectome™ system is designed for performing trabeculectomy via an ab interno approach. It successfully removed sections of trabecular meshwork and Schlemms canal inner wall with less injury to the adjacent tissue compared with goniotomy knife in vitro. Theoretically, this procedure should provide direct access of aqueous humor to Schlemms canal.

Changes in axial length following trabeculectomy and glaucoma drainage device surgery

Aim: This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery. Methods: This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute. Patient population: One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma. Intervention: These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and >3 months after surgery. Main outcome measures: Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0−4 mm Hg), low (5−9), normal (10−17), and high (18 or more). Results: There was a statistically significant reduction in IOP after 3 months of −12.8 (SD 1.5) mm Hg following trabeculectomy (p<0.001), and −10.7 (1.9) mm Hg after GDD (p<0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p<0.001), of −0.15 (0.03) and −0.21 (0.04) mm (1 week), −0.18 (0.02) and −0.10 (0.02) mm (1 month), and −0.16 (0.03) and −0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p<0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (−0.39 (0.11)) that was statistically significantly lower (p<0.01) than the other trabeculectomy eyes (−0.14 (0.15)). Conclusions: There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = −199+0.006×IOP reduction+0.008×final IOP.

Ab Interno Trabeculectomy Versus Trabeculectomy for Open-Angle Glaucoma

PURPOSE To compare the effect of ab interno trabeculectomy with trabeculectomy. DESIGN Retrospective, cohort study. PARTICIPANTS A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age ≥ 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. METHODS Clinical variables were collected from patient medical records. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP ≤ 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. RESULTS Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 ± 8.6 mmHg at baseline to 15.9 ± 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 ± 10.9 mmHg at baseline to 10.2 ± 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P<0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P<0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P<0.001). CONCLUSIONS Ab interno trabeculectomy has a lower success rate than trabeculectomy. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Laser Trabeculoplasty for Open-Angle Glaucoma A Report by the American Academy of Ophthalmology

OBJECTIVE To provide an evidence-based summary of the outcomes, repeatability, and safety of laser trabeculoplasty for open-angle glaucoma. METHODS A search of the peer-reviewed literature in the PubMed and the Cochrane Library databases was conducted in June 2008 and was last repeated in March 2010 with no date or language restrictions. The search yielded 637 unique citations, of which 145 were considered to be of possible clinical relevance for further review and were included in the evidence analysis. RESULTS Level I evidence indicates an acceptable long-term efficacy of initial argon laser trabeculoplasty for open-angle glaucoma compared with initial medical treatment. Among the remaining studies, level II evidence supports the efficacy of selective laser trabeculoplasty for lowering intraocular pressure for patients with open-angle glaucoma. Level III evidence supports the efficacy of repeat use of laser trabeculoplasty. CONCLUSIONS Laser trabeculoplasty is successful in lowering intraocular pressure for patients with open-angle glaucoma. At this time, there is no literature establishing the superiority of any particular form of laser trabeculoplasty. The theories of action of laser trabeculoplasty are not elucidated fully. Further research into the differences among the lasers used in trabeculoplasty, the repeatability of the procedure, and techniques of treatment is necessary. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Baseline Risk Factors that Predict the Development of Open-Angle Glaucoma in a Population: The Los Angeles Latino Eye Study

OBJECTIVE To determine which baseline sociodemographic, lifestyle, anthropometric, clinical, and ocular risk factors predict the development of open-angle glaucoma (OAG) in an adult population. DESIGN A population-based, prospective cohort study. PARTICIPANTS A total of 3772 self-identified Latinos aged ≥40 years from Los Angeles, California, who were free of OAG at baseline. METHODS Participants from the Los Angeles Latino Eye Study had standardized study visits at baseline and 4-year follow-up with structured interviews and a comprehensive ophthalmologic examination. We defined OAG as the presence of an open angle and a glaucomatous visual field abnormality and/or evidence of glaucomatous optic nerve damage in ≥1 eye. Multivariate logistic regression with stepwise selection was performed to determine which potential baseline risk factors independently predict the development of OAG. MAIN OUTCOME MEASURES Odds ratios for various risk factors. RESULTS Over the 4-year follow-up, 87 participants developed OAG. The baseline risk factors that predict the development of OAG include older age (odds ratio [OR] per decade, 2.19; 95% confidence interval [CI], 1.74-2.75; P<0.001), higher intraocular pressure (IOP; OR per mmHg, 1.18; 95% CI, 1.10-1.26; P<0.001), longer axial length (OR per mm, 1.48; 95% CI, 1.22-1.80; P<0.001), thinner central cornea (OR per 40 μm thinner, 1.30; 95% CI, 1.00-1.70; P = 0.050), higher waist-to-hip ratio (OR per 0.05 higher, 1.21; 95% CI, 1.05-1.39; P = 0.007) and lack of vision insurance (OR, 2.08; 95% CI, 1.26-3.41; P = 0.004). CONCLUSIONS Despite a mean baseline IOP of 14 mmHg in Latinos, higher IOP is an important risk factor for developing OAG. Biometric measures suggestive of less structural support such as longer axial length and thin central corneal thickness were identified as important risk factors. Lack of health insurance reduces access to eye care and increases the burden of OAG by reducing the likelihood of early detection and treatment of OAG. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Relationship among Visual Field, Blood Flow, and Neural Structure Measurements in Glaucoma

PURPOSE To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. METHODS Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale. RESULTS Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03). CONCLUSIONS There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.

Intraocular Pressure, Central Corneal Thickness, and Prevalence of Open-Angle Glaucoma: The Los Angeles Latino Eye Study

PURPOSE To examine the relationship between the prevalence of open-angle glaucoma (OAG) and intraocular pressure (IOP) and the impact of central corneal thickness (CCT) on this relationship. DESIGN Population-based cross-sectional study. METHODS The study cohort consisted of 5,970 participants from the Los Angeles Latino Eye Study (LALES) with no history of glaucoma treatment and with complete ophthalmic examination data. The relationship between the prevalence of OAG and IOP was contrasted across persons with CCT designated as thin, normal, or thick. RESULTS Prevalence of OAG was exponentially related to IOP. When stratified by CCT, persons with thin CCT had a significantly higher prevalence of OAG than did those with normal or thick CCTs at all levels of IOP. Adjusting each IOP individually for CCT did not impact significantly the relationship between the prevalence of OAG and IOP. CONCLUSIONS These findings suggest that adjusting for the impact of CCT on IOP by correction algorithms is not necessary in a population based assessment of glaucoma prevalence; CCT, however, is an important independent risk factor for the prevalence of OAG.