Faculty Bibliography

PURPOSE/OBJECTIVE:To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. DESIGN/METHODS:Multicenter cohort study. METHODS:Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. RESULTS:A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. CONCLUSION/CONCLUSIONS:Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model.

Vascularized composite allotransplantation represents a potential shift in approaches to reconstruction of complex defects resulting from congenital differences as well as trauma and other acquired pathology. Given the highly specialized function of the eye and its unique anatomical components, vascularized composite allotransplantation of the eye is an appealing method for restoration, replacement, and reconstruction of the nonfunctioning eye. Herein, we describe conventional treatments for eye restoration and their shortcomings as well as recent research and events that have brought eye transplantation closer to a potential clinical reality. In this article, we outline some potential considerations in patient selection, donor facial tissue procurement, eye tissue implantation, surgical procedure, and potential for functional outcomes.

PURPOSE/OBJECTIVE:To 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. METHODS:This 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. RESULTS:Of 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). CONCLUSIONS:This 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.

Whole eye transplantation (WET) remains experimental. Long presumed impossible, recent scientific advances regarding WET suggest that it may become a clinical reality. However, the ethical implications of WET as an experimental therapeutic strategy remain largely unexplored. This article evaluates the ethical considerations surrounding WET as an emerging experimental treatment for vision loss. A thorough review of published literature pertaining to WET was performed; ethical issues were identified during review of the articles.

PURPOSE/OBJECTIVE: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/CONCLUSIONS:Phacoemulsification does not make a significant contribution to postoperative IOP or number of medications when combined with trabectome surgery in phakic patients.

PURPOSE:To report diagnostic accuracy of optical coherence tomography (OCT) disc variables using both time-domain (TD) and Fourier-domain (FD) OCT, and to improve the use of OCT disc variable measurements for glaucoma diagnosis through regression analyses that adjust for optic disc size and axial length-based magnification error. DESIGN:Observational, cross-sectional. PARTICIPANTS:In total, 180 normal eyes of 112 participants and 180 eyes of 138 participants with perimetric glaucoma from the Advanced Imaging for Glaucoma Study. METHODS:Diagnostic variables evaluated from TD-OCT and FD-OCT were: disc area, rim area, rim volume, optic nerve head volume, vertical cup-to-disc ratio (CDR), and horizontal CDR. These were compared with overall retinal nerve fiber layer thickness and ganglion cell complex. Regression analyses were performed that corrected for optic disc size and axial length. Area-under-receiver-operating curves (AUROC) were used to assess diagnostic accuracy before and after the adjustments. An index based on multiple logistic regression that combined optic disc variables with axial length was also explored with the aim of improving diagnostic accuracy of disc variables. MAIN OUTCOME MEASURE:Comparison of diagnostic accuracy of disc variables, as measured by AUROC. RESULTS:The unadjusted disc variables with the highest diagnostic accuracies were: rim volume for TD-OCT (AUROC=0.864) and vertical CDR (AUROC=0.874) for FD-OCT. Magnification correction significantly worsened diagnostic accuracy for rim variables, and while optic disc size adjustments partially restored diagnostic accuracy, the adjusted AUROCs were still lower. Axial length adjustments to disc variables in the form of multiple logistic regression indices led to a slight but insignificant improvement in diagnostic accuracy. CONCLUSIONS:Our various regression approaches were not able to significantly improve disc-based OCT glaucoma diagnosis. However, disc rim area and vertical CDR had very high diagnostic accuracy, and these disc variables can serve to complement additional OCT measurements for diagnosis of glaucoma.

PURPOSE/OBJECTIVE:We studied the effects of age and intraocular pressure (IOP) on retinal nerve fiber layer (NFL) and macular ganglion cell complex (GCC) thickness in normal eyes. METHODS:Data from subjects from the multicenter Advanced Imaging for Glaucoma Study (AIGS) were analyzed. The data included yearly visits from the normal subjects in the AIGS study. Fourier-domain optical coherence tomography (FD-OCT) was used to measure retinal NFL and macular GCC on each visit. Mixed effect models were used to evaluate the longitudinal effect of age and IOP on the NFL and GCC thickness. The measurements at baseline were used to examine the cross-sectional effects. RESULTS:< 0.001). There was no significant IOP effect on either GCC or NFL from either the longitudinal or cross-sectional analysis. CONCLUSIONS:Longitudinal and cross-sectional analyses provided consistent rates of approximately 0.2% per year of age-related thinning in NFL and GCC thicknesses. This is relevant in establishing criteria to detect glaucoma-related thinning (disease progression) in excess of normal aging. IOP does not seem to be a significant confounder for progression analysis. TRANSLATIONAL RELEVANCE/UNASSIGNED:This study demonstrated the relevance of advanced imaging technology in diagnosing and monitoring glaucoma disease.

We analysed all of the PubMed publications on ab-interno trabeculectomy (AIT) with the Trabectome (Neomedix, Irvine, California, USA) to determine the reduction in intraocular pressure (IOP) and medications following the procedure. For IOP outcomes, PubMed was searched for 'trabectome', 'ab interno trabeculotomy' and 'ab interno trabeculectomy' and all available papers retrieved. The meta-analysis used a random-effects model to achieve conservative estimates and assess statistical heterogeneity. To investigate complications, we included all abstracts from the American Glaucoma Society, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery and the Association for Research in Vision and Ophthalmology. The overall arithmetic mean baseline IOP for standalone Trabectome was 26.71±1.34 mm Hg and decreased by 10.5±1.9 mm Hg (39% decrease) on 0.99±0.54 fewer medications. Defining success as IOP ≤21 with a 20% decrease while avoiding reoperation, the overall average success rate after 2 years was 46±34%. For combined phacoemulsification-Trabectome, the baseline IOP of 21±1.31 mm Hg decreased by 6.24±1.98 mm Hg (27% decrease) on 0.76±0.35 fewer medications. The success rate using the same definition at 2 years was 85±7%. The weighted mean IOP difference from baseline to study endpoint was 9.77 mm Hg (95% CI 8.90 to 10.64) standalone and 6.04 mm Hg (95% CI 4.95 to 7.13) for combined cases. Despite heterogeneity, meta-analysis showed significant and consistent decrease in IOP and medications from baseline to end point in AIT and phaco-AIT. The rate of visually threatening complications was <1%. On average, trabectome lowers the IOP by approximately 31% to a final IOP near 15 mm Hg while decreasing the number of medications by less than one, with a low rate of serious complications. After 2 years, the overall average success rate is 66%.