Faculty Bibliography

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.

Trabecular bypass was first used as a surgical treatment for glaucoma more than 100 years ago and aims to circumvent the trabecular meshwork, thought to be the main site of aqueous humor outflow resistance. The emerging field of microinvasive glaucoma surgery has brought a new ab interno trabecular microbypass stent through the U.S. Food and Drug Administration-approval process, and data from long-term randomized prospective trials have shown the safety and intraocular pressure-lowering value of trabecular microbypass. This review discusses the historical evolution of trabecular microbypass and describes new and forthcoming surgical options along with available clinical safety and efficacy data. FINANCIAL DISCLOSURE: Proprietary or commercial disclosures are listed after the references.

PURPOSE: To highlight changing features over time within a single static image through the auto-alignment and subtraction of serial optic nerve photographs. METHODS: Subtraction maps were generated from auto-aligned (EyeIC, Narbeth, PA) baseline and follow-up images using Adobe Photoshop software. They demonstrated progressive retinal nerve fibre layer (RNFL) defects, optic disc haemorrhage (DH), neuroretinal rim loss (RL) and peripapillary atrophy (PPA). A masked glaucoma specialist identified features of progression on subtraction map first, then assessed feature strength by comparison with original images using alternation flicker. Control images with no progression and parallax-only images (as determined by flicker) were included. RESULTS: Eighty eyes of 67 patients were used to generate subtraction maps that detected glaucoma progression in 87% of DH (n = 28, sensitivity (Se) 82%, specificity (Sp) 98%) and 84% of PPA (n = 30, Se 80%, Sp 98%) cases. The lowest rate of detection was seen with RL at 67% (n = 31, Se 65%, Sp 100%). The subtraction technique was most sensitive for detecting parallax (n = 39, Se 98%, Sp 94%). Features of glaucoma progression appeared equally strong in flicker and subtraction images, but parallax was often enhanced on subtraction maps. Among control images selected for absence of features of glaucomatous change (n = 9) in original flicker images, no features were detected on subtraction maps. CONCLUSIONS: Auto-alignment and subtraction of serial optic nerve photographs reliably detects features of glaucoma progression with a single static image. Parallax identification may also be facilitated. Auto-alignment and subtraction of serial optic nerve photographs may prove especially useful in education and printed publications when dynamic imaging is not feasible.

PURPOSE: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with >/=8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<-0.02 decibels [dB]/year), moderate (-0.02 to -0.65 dB/year), or fast (>/=-0.65 dB/year) progression. To determine whether graders' assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. METHODS: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). MAIN OUTCOME MEASURES: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. RESULTS: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P = 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P< 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs. -0.29 dB/year; 95% confidence interval [CI], 0.03-0.48); P = 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P = 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1-4.5; P = 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7-83.6; P< 0.001) and DH (OR, 4.6; 95% CI, 1.5-15.5; P< 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. CONCLUSIONS: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.

Glaucoma is a progressive optic neuropathy characterized by functional visual loss and underlying optic nerve deterioration. Optic nerve imaging, achieved using photography and scanning ophthalmic laser diagnostic imaging techniques, is an important aspect of glaucoma diagnosis and management. Alternation flicker is a technique in which serial optic nerve photographs, typically taken one or more years apart, are aligned and alternated in order to allow the observer to easily detect change over time. Alternation flicker has been shown to improve several aspects of optic nerve evaluation and has been demonstrated to correlate with traditional glaucoma risk factors, with some limitations. In this review, we consider the literature with respect to flicker for the evaluation and monitoring of glaucomatous optic neuropathy

Purpose: Optic disc haemorrhages are associated with active glaucomatous neurodegeneration and ongoing visual field loss. We sought to determine whether automated alternation flicker enhances the detection of disc haemorrhages in serial images from patients with glaucoma when compared to side-by-side photographic evaluation and single-image display. Methods: Serial sets of optic nerve photographs of 394 eyes from 234 patients followed for glaucoma at the authors' institutions were included in this study. Eyes with disc haemorrhages were graded for difficulty level and randomized along with nondisc haemorrhage control images into one of three presentation groups (automated alternation flicker, side-by-side or single image). Seven graders viewed all images and assessed for the presence or absence of disc haemorrhages. Results: The sensitivity of automated alternation flicker for disc haemorrhage detection (0.878) was higher than side-by-side (0.705; p = 0.002) and single photographs (0.757; p = 0.01). There was no specificity difference between pairs of presentation groups (all p >/= 0.7). Conclusion: Automated alternation flicker was a more sensitive method for disc haemorrhage detection than the current clinical standards and may have an important role in the management of glaucoma

PURPOSE: To measure accuracy and speed for detection of vascular progression in retinopathy of prematurity (ROP) from serial images. Two strategies are compared: static side-by-side presentation and dynamic flickering of superimposed image pairs. DESIGN: Prospective comparative study. METHODS: Fifteen de-identified, wide-angle retinal image pairs were taken from infants who eventually developed plus disease. Image pairs representing vascular disease progression were taken >/=1 week apart, and control images without progression were taken on the same day. Dynamic flickering pairs were created by digital image registration. Ten experts independently reviewed each image pair on a secure website using both strategies, and were asked to identify progression or state that images were identical. Accuracy and speed were measured, using examination date and ophthalmoscopic findings as a reference standard. RESULTS: Using static images, experts were accurate in a mean (%) +/- standard deviation (SD) of 11.4 of 15 (76%) +/- 1.7 image pairs. Using dynamic flickering images, experts were accurate in a mean (%) +/- SD of 11.3 of 15 (75%) +/- 1.7 image pairs. There was no significant difference in accuracy between these strategies (P = .420). Diagnostic speed was faster using dynamic flickering (24.7 +/- 8.3 seconds) vs static side-by-side images (40.3 +/- 18.3 seconds) (P = .002). Experts reported higher confidence when interpreting dynamic flickering images (P = .001). CONCLUSIONS: Retinal imaging provides objective documentation of vascular appearance, with potentially improved ability to recognize ROP progression compared to standard ophthalmoscopy. Speed of identifying vascular progression was faster by review of dynamic flickering image pairs than by static side-by-side images, although there was no difference in accuracy.

Aims To evaluate corneal hysteresis (CH) and intraocular pressure (IOP) before and after IOP lowering with prostaglandin analogue (PGA) therapy in medication-naive eyes. Methods In this retrospective study, we included records from 57 consecutive patients with open angle glaucoma who were initiated on PGA. Patients underwent ocular response analyser measurement with IOP assessment at baseline (untreated) and at follow-up (treated). Results Median follow-up time between IOP measurements was 1.4 (range 0.4-13.5) months. IOP was reduced by 3.2 mm Hg (18.8%) from 17.0 to 13.8 mm Hg (p<0.001). CH increased by 0.5 mm Hg (5.2%) from 9.7 to 10.2 mm Hg (p=0.02). Baseline CH (but not baseline central corneal thickness) was a significant predictor of the magnitude of IOP reduction, with patients in the lowest quartile of CH (mean 7.0 mm Hg) experiencing a 29.0% reduction in IOP while those in the highest CH quartile (mean 11.9 mm Hg) experienced a 7.6% reduction in IOP (p=0.006). A multivariate analysis controlling for baseline IOP demonstrated that baseline CH independently predicted the magnitude of IOP reduction with PGA therapy in both per cent (ss=3.5, p=0.01) and absolute (ss=0.6, p=0.02) terms. Conclusion Although CH is influenced by IOP, baseline CH is independently associated with the magnitude of IOP reduction with PGA therapy

As choroidal changes have been suggested in glaucoma, we examined peripapillary choroidal thickness (CT) in patients with and without primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT). We collected measurements retrospectively on 70 eyes of 70 patients consecutively undergoing SD-OCT. POAG (n = 31) and suspect eyes (n = 39) had two reliable and repeatable Humphrey 24-2 visual fields with glaucoma hemifield test outside or within normal limits, respectively. A 360-degree peripapillary scan was performed using the standard protocol for retinal nerve fiber layer (RNFL) assessment. Using provided software, two independent masked investigators manually segmented CT as the area of visible choroidal vasculature. Agreement between investigators was determined using Lin's concordance correlation coefficient (CCC). A single masked observer determined clock hours of parapapillary atrophy (PPA) and the presence of ssPPA for each optic nerve quadrant. Correlation between RNFL and CT was assessed; two-sample t-tests were used to determine differences in RNFL and CT between POAG and suspect eyes; and linear regression was used to model changes in RNFL and CT. We found that independent measurements of CT by two observers were highly correlated (Lin's CCC for global CT; rho(c) = 0.93, p < 0.001). RNFL and CT measurements were not significantly correlated for any peripapillary location (|r| </= 0.15, p >/= 0.22). Global CT (ss = -1.94, 95% confidence interval [CI] -2.76, -1.13) but not RNFL thickness (ss = -0.18, 95% CI -0.58, 0.22) decreased significantly with age. Compared to suspect eyes, eyes with POAG had significantly thinner RNFL measurements at all locations (p </= 0.005) but CT measurements did not differ between groups for any location (p >/= 0.13). Adjusting for glaucoma status and age, total (ss = 3.15 95% CI -0.24, 6.53) and ss clock hours of PPA (ss = 1.33, 95% CI -1.72, 4.38) were not significantly associated with global CT; the spatial distribution of PPA was not associated with underlying CT, though PPA was graded subjectively and may have been subject to spatial mismatch with a singular peripapillary eccentricity on SD-OCT. We conclude that eyes with POAG did not demonstrate reduced CT nor was there a correlation between RNFL and CT maps. This study does not support the use of CT assessment in glaucoma diagnosis or management