Review of Longitudinal Glaucoma Progression: 5 Years after the Shaffer Lecture.

In 2013, the senior author delivered the American Academy of Ophthalmology Robert N. Shaffer Lecture entitled "Glaucoma Changes-Reality Bites." This talk focused on describing the longitudinal structure-function relationships in glaucoma progression. The study was based on a 10-year longitudinal dataset created by calibrated measurements across multiple OCT generations with corresponding visual fields (VFs). The prior held observation was that functional damage follows structural damage. The lecture posited that structure and function change at similar times, but that current measurement technology limits our ability to detect functional abnormalities and change early in glaucoma, as well as to measure structural change late in the disease. The Shaffer lecture provided evidence that structure and function change concordantly and that any apparent discordance in the relationship was due to technologic limitations to measure glaucomatous change. Furthermore, we observed 5 longitudinal relationships of concordance and discordance that can exist with structure-function interactions. Concordance: (1) structure-structure progression, (2) structure-function tipping point, (3) structural floor tipping point. Discordance: (4) functional progression in a "stable" VF with structure-function correlation, (5) functional progression with "normal" structure. In this review article, we will review longitudinal glaucoma progression studies with long-term follow-up and discuss the clinical relevance of relationships of concordance and discordance that can exist with structure-function interactions.

In-vivo effects of intraocular and intracranial pressures on the lamina cribrosa microstructure.

There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health.

Longer-term Baerveldt to Trabectome glaucoma surgery comparison using propensity score matching.

PURPOSE: To apply propensity score matching to compare Baerveldt glaucoma drainage implant (BGI) to Trabectome-mediated ab interno trabeculectomy (AIT). Recent data suggests that AIT can produce results similar to BGI which is traditionally reserved for more severe glaucoma. METHODS: BGI and AIT patients with at least 1 year of follow-up were included. The primary outcome measures were intraocular pressure (IOP), number of glaucoma medications, and a Glaucoma Index (GI) score. GI reflected glaucoma severity based on visual field, the number of preoperative medications, and preoperative IOP. Score matching used a genetic algorithm consisting of age, gender, type of glaucoma, concurrent phacoemulsification, baseline number of medications, and baseline IOP. Patients with neovascular glaucoma, with prior glaucoma surgery, or without a close match were excluded. RESULTS: Of 353 patients, 30 AIT patients were matched to 29 BGI patients. Baseline characteristics including, IOP, the number of glaucoma medications, type of glaucoma, the degree of VF loss and GI were not significantly different between AIT and BGI. BGI had a preoperative IOP of 21.6 ± 6.3 mmHg compared to 21.5 ± 7.4 for AIT on 2.8 ± 1.1 medications and 2.5 ± 2.3 respectively. At 30 months, the mean IOP was 15.0 ± 3.9 mmHg for AIT versus 15.0 ± 5.7 mmHg for BGI (p > 0.05), while the number of drops was 1.5 ± 1.3 for AIT (change: p = 0.001) versus 2.4 ± 1.2 for BGI (change: p = 0.17; AIT vs BGI: 0.007). Success, defined as IOP < 21 mmHg, < 20% reduction and no reoperation, was achieved at 1 year in 56% of AIT versus 55% of BGI (p > 0.05) and 50% versus 52% at 2.5 years. CONCLUSIONS: A propensity score matched comparison of AIT and BGI demonstrated a similar IOP reduction through 1 year. AIT required fewer medications.

Decreased Lamina Cribrosa Beam Thickness and Pore Diameter Relative to Distance From the Central Retinal Vessel Trunk.

PURPOSE: To investigate how the lamina cribrosa (LC) microstructure changes with distance from the central retinal vessel trunk (CRVT), and to determine how this change differs in glaucoma. METHODS: One hundred nineteen eyes (40 healthy, 29 glaucoma suspect, and 50 glaucoma) of 105 subjects were imaged using swept-source optical coherence tomography (OCT). The CRVT was manually delineated at the level of the anterior LC surface. A line was fit to the distribution of LC microstructural parameters and distance from CRVT to measure the gradient (change in LC microstructure per distance from the CRVT) and intercept (LC microstructure near the CRVT). A linear mixed-effects model was used to determine the effect of diagnosis on the gradient and intercept of the LC microstructure with distance from the CRVT. A Kolmogorov-Smirnov test was applied to determine the difference in distribution between the diagnostic categories. RESULTS: The percent of visible LC in all scans was 26 ± 7%. Beam thickness and pore diameter decreased with distance from the CRVT. Glaucoma eyes had a larger decrease in beam thickness (-1.132 ± 0.503 µm, P = 0.028) and pore diameter (-0.913 ± 0.259 µm, P = 0.001) compared with healthy controls per 100 µm from the CRVT. Glaucoma eyes showed increased variability in both beam thickness and pore diameter relative to the distance from the CRVT compared with healthy eyes (P < 0.05). CONCLUSIONS: These findings results demonstrate the importance of considering the anatomical location of CRVT in the assessment of the LC, as there is a relationship between the distance from the CRVT and the LC microstructure, which differs between healthy and glaucoma eyes.

Glaucoma Structural and Functional Progression in American and Korean Cohorts.

PURPOSE: To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months. METHODS: All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits. MAIN OUTCOME MEASUREMENTS: The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. RESULTS: The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 µm/year vs. -0.24 µm/year; P < 0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. CONCLUSIONS: Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.

New developments in optical coherence tomography.

PURPOSE OF REVIEW: Optical coherence tomography (OCT) has become the cornerstone technology for clinical ocular imaging in the past few years. The technology is still rapidly evolving with newly developed applications. This manuscript reviews recent innovative OCT applications for glaucoma diagnosis and management. RECENT FINDINGS: The improvements made in the technology have resulted in increased scanning speed, axial and transverse resolution, and more effective use of the OCT technology as a component of multimodal imaging tools. At the same time, the parallel evolution in novel algorithms makes it possible to efficiently analyze the increased volume of acquired data. SUMMARY: The innovative iterations of OCT technology have the potential to further improve the performance of the technology in evaluating ocular structural and functional characteristics and longitudinal changes in glaucoma.

Evaluating glaucoma damage: emerging imaging technologies.

The use of ocular imaging tools to estimate structural and functional damage in glaucoma has become a common clinical practice and a substantial focus of vision research. The evolution of the imaging technologies through increased scanning speed, penetration depth, image registration and development of multimodal devices has the potential to detect the pathology more reliably and in earlier stages. This review is focused on new ocular imaging modalities used for glaucoma diagnosis.