Intraocular Pressure Fluctuation: Is It Important?

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma. Previous prospective, randomized, long-term studies have demonstrated the strength of IOP reduction in slowing the progression of disease. It is well known that IOP is not a fixed value but fluctuates considerably over time. Although there have been some studies on IOP fluctuation and the progression of glaucoma, whether IOP fluctuation is an independent risk factor for glaucomatous damage and disease progression remains controversial. In this article, we reviewed the definition of IOP fluctuation, and both the evidence and the speculation for and against the effect of IOP fluctuation on glaucoma progression. Although conclusions seem to vary from study to study, we considered that different studies examined different groups of patients, at different stages of disease, and at different IOP levels. Our conclusion is that these apparently disparate results are not conflicting, but rather can be viewed as complementary. In clinical care, we recommend the consideration of IOP "modulation" rather than just IOP "reduction" when glaucoma patients are treated. Quality-based IOP control may be more effective than quantity-based IOP reduction to prevent or retard disease progression

Prevalence and spatial concordance of visual field deterioration in fellow eyes of glaucoma patients.

PurposeTo examine the prevalence of visual field deterioration in contralateral eyes of patients with worsening open-angle glaucoma and to evaluate the spatial concordance of visual field deterioration between both eyes.MethodsOne hundred sixteen open-angle glaucoma patients who underwent 8 or more visual field examinations over ≥ 6 years of follow-up were included. The rates of the fast and slow components of visual field decay for each of 52 visual field test locations were calculated with point-wise exponential regression analysis. The spatial concordance of visual field deterioration in contralateral eyes was evaluated with a concordance ratio (calculated as the number of overlapping locations divided by the total number of deteriorating locations) and by comparing the rate of decay in corresponding modified glaucoma hemifield test clusters.ResultsThe average visual field mean deviation (± standard deviation [SD]) was -8.5 (± 6.4) dB and the mean (± SD) follow-up time was 9.0 (± 1.6) years. Sixty-three patients had mild damage, 23 had moderate damage, and 30 had severe damage. The mean concordance ratio (± SD) was 0.46 (± 0.32) for the mild group, 0.33 (± 0.27) for the moderate group, and 0.35 (± 0.21) for the severe group. Thirty-one patients (27%) had deterioration in concordant locations (p < 0.05). Visual field deterioration was greater in the superior hemifield than the inferior hemifield (p < 0.05) when evaluated with both the concordance ratio and modified glaucoma hemifield test cluster analysis methods.ConclusionsThere is only fair spatial concordance with regard to visual field deterioration between the both eyes of an individual. We conclude that testing algorithms taking advantage of inter-eye spatial concordance would not be particularly advantageous in the early detection of glaucomatous deterioration

The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in Normal and Glaucoma Subjects.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P < 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P > 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH

Comparative lipid profiling dataset of the inflammation-induced optic nerve regeneration.

In adult mammals, retinal ganglion cells (RGCs) fail to regenerate following damage. As a result, RGCs die after acute injury and in progressive degenerative diseases such as glaucoma; this can lead to permanent vision loss and, eventually, blindness. Lipids are crucial for the development and maintenance of cell membranes, myelin sheaths, and cellular signaling pathways, however, little is known about their role in axon injury and repair. Studies examining changes to the lipidome during optic nerve (ON) regeneration could greatly inform treatment strategies, yet these are largely lacking. Experimental animal models of ON regeneration have facilitated the exploration of the molecular determinants that affect RGC axon regeneration. Here, we analyzed lipid profiles of the ON and retina in an ON crush rat model using liquid chromatography-mass spectrometry. Furthermore, we investigated lipidome changes after ON crush followed by intravitreal treatment with Zymosan, a yeast cell wall derivative known to enhance RGC regeneration. This data is available at the NIH Common Fund's Metabolomics Data Repository and Coordinating Center (supported by NIH grant, U01-DK097430) website, the Metabolomics Workbench, http://www.metabolomicsworkbench.org, where it has been assigned Project ID: PR000661. The data can be accessed directly via it's Project DOI: doi: 10.21,228/M87D53

Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR).

PurposeThe study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma.MethodsWe studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway-Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions.ResultsThe mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64.ConclusionsSmoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR.Translational relevanceThe application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions

Cataract surgery in eyes with filtered primary angle closure glaucoma.

PurposeTo evaluate the effect of cataract surgery on intraocular pressure (IOP) in filtered eyes with primary angle closure glaucoma (PACG).MethodsIn this prospective interventional case series, 37 previously filtered eyes from 37 PACG patients with mean age of 62.1±10.4 years were consecutively enrolled. All patients had visually significant cataracts and phacoemulsification was performed at least 12 months after trabeculectomy. Visual acuity, IOP and the number of glaucoma medications were recorded preoperatively, and 1, 3, 6 and 12 months after surgery. Anterior chamber (AC) depth was measured preoperatively and 3 months after cataract surgery with A-scan ultrasonography. The main outcome measure was IOP at 12 months.ResultsIOP was decreased significantly from 18.16±5.91 mmHg at baseline to 15.37±2.90 mmHg at final follow-up (P<0.01). The mean number of glaucoma medications was significantly decreased from 1.81±0.24 to 0.86±1.00 (P=0.001) at 1 year postoperatively. At final follow up, 36 (97.2%) eyes and 32 (86.4%) eyes had IOP≤21 and IOP≤18 mmHg, respectively; 14 (37.8%) eyes and 9 (24.3%) eyes had IOP≤21 and IOP≤18 mmHg without medications, respectively. The magnitude of IOP reduction was correlated with higher preoperative IOP (r=0.85, P<0.001), shallower preoperative AC depth (r=-0.38, P=0.01) and greater changes in AC depth (r=-0.39, P=0.01).ConclusionCataract surgery reduces IOP and the number of glaucoma medications in previously filtered PACG eyes. This reduction seems to be greater in patients with higher preoperative IOP and shallower anterior chambers

Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure.

PurposeWe used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).MethodsSeventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.ResultsAverage mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).ConclusionsAlthough tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP

Peripapillary and macular choroidal thickness in glaucoma.

PurposeTo compare choroidal thickness (CT) between individuals with and without glaucomatous damage and to explore the association of peripapillary and submacular CT with glaucoma severity using spectral domain optical coherence tomography (SD-OCT).MethodsNinety-one eyes of 20 normal subjects and 43 glaucoma patients from the UCLA SD-OCT Imaging Study were enrolled. Imaging was performed using Cirrus HD-OCT. Choroidal thickness was measured at four predetermined points in the macular and peripapillary regions, and compared between glaucoma and control groups before and after adjusting for potential confounding variables.ResultsThe average (± standard deviation) mean deviation (MD) on visual fields was -0.3 (±2.0) dB in controls and -3.5 (±3.5) dB in glaucoma patients. Age, axial length and their interaction were the most significant factors affecting CT on multivariate analysis. Adjusted average CT (corrected for age, axial length, their interaction, gender and lens status) however, was not different between glaucoma patients and the control group (P=0.083) except in the temporal parafoveal region (P=0.037); nor was choroidal thickness related to glaucoma severity (r=-0.187, P=0.176 for correlation with MD, r=-0.151, P=0.275 for correlation with average nerve fiber layer thickness).ConclusionsChoroidal thickness of the macular and peripapillary regions is not decreased in glaucoma. Anatomical measurements with SD-OCT do not support the possible influence of the choroid on the pathophysiology of glaucoma

Vertical Macular Asymmetry Measures Derived From SD-OCT for Detection of Early Glaucoma.

PurposeTo test the hypothesis that vertical asymmetry in macular ganglion cell/inner plexiform layer (GCIPL) thickness can improve detection of early glaucoma.MethodsSixty-nine normal eyes and 101 glaucoma eyes had macular imaging with spectral-domain optical coherence tomography (OCT; 200 × 200 cube). The resulting GCIPL thickness matrix was grouped into a 20 × 20 superpixel array and superior superpixels were compared to their inferior counterparts. A global asymmetry index (AI) was defined as the grand mean of the asymmetry ratios. To measure local asymmetry, the corresponding thickness measurements of three rows above and below the horizontal raphe were compared individually and in combinations. Global and local AIs were compared to the best-performing GCIPL thickness parameters with area under the receiver operating curves (AUC) and sensitivity/specificities.ResultsAge or axial length did not influence AIs in normal subjects (P ≥ 0.08). Global and local AIs were significantly higher in the glaucoma group compared to normal eyes. Minimum (AUC = 0.962, 95% confidence interval [CI]: 0.936-0.989) and inferotemporal thickness (AUC = 0.944, 95% CI: 0.910-0.977; P = 0.122) performed best for detection of early glaucoma. The AUC for global AI was 0.851 (95% CI: 0.792-0.909) compared to 0.916 (95% CI: 0.874-0.958) for the best local AI. Combining minimum or inferotemporal GCIPL thickness and the best local AI led to higher partial AUCs (0.088 and 0.085, 90% specificity, P = 0.120 and 0.130, respectively) than GCIPL thickness measures.ConclusionsMacular vertical thickness asymmetry measures did not perform better than sectoral or minimum GCIPL thickness for detection of early glaucoma. Combining local asymmetry parameters with the best sectoral GCIPL thickness measures enhanced this task

Comparison of Outcomes between Endoscopic and Transcleral Cyclophotocoagulation.

Importance: Traditionally cyclophotocoagulation has been reserved as a treatment of last resort for eyes with advanced stage glaucoma, but increasingly it is offered to eyes with less severe disease. Endoscopic approaches in particular are utilized in increasing numbers of patients despite only a small number of publications on its results. Objective: The purpose of this study was to compare the efficacy and safety of endoscopic and transcleral cyclophotocoagulation (ECP and TCP) procedures in eyes with refractory glaucomas. Design, Setting, and Participants: A chart review was performed on consecutive patients who underwent ECP and TCP at a tertiary ophthalmology care center between January 2000 and December 2010. Cases with fewer than 3 months of follow-up or that had concurrent pressure reducing procedures were excluded. The main outcome measures examined were intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), additional glaucoma procedure required, and complications. Main Outcomes and Measures: Forty-two eyes (42 patients) that underwent ECP and forty-four eyes (44 patients) that underwent TCP were identified. The TCP group had a statistically higher mean age (71.2 ± 16.7 vs. 58.1 ± 22.9 years, respectively), larger proportion of neovascular glaucoma (40.9% vs. 16.7%), worse initial BCVA (logMAR 2.86 vs. 1.81), and higher preoperative IOP (45.3 vs. 26.6 mmHg) than the ECP group. At 12 months follow-up, the mean IOP difference between groups was not statistically significant, although the change in IOP from baseline to 12 months was greater for the TCP group (p = 0.006). The rates of progression to no light perception (NLP) and phthisis bulbi were significantly higher amongst TCP eyes than ECP eyes (27.2% vs. 4.8%, p = 0.017, and 20.5% vs. 0%, p = 0.003, respectively). Of these eyes that progressed, a majority had neovascular glaucoma (NVG). Corneal decompensation was the most frequent complication following ECP (11.9%). Conclusions and Relevance: In patients with preoperative BCVA of 20/400 or better, overall complication rates (cystoid macular edema, exudative retinal detachment, inflammation, cornea decompensation) were higher after ECP than with TCP. In refractory glaucomas in a real world setting (not a trial), TCP was more frequently used in ischemic eyes. TCP was associated with a higher rate of progression to phthisis bulbi and loss of light perception than ECP. However, ECP was associated with a clinically significant rate of corneal decompensation. These outcomes likely were related to the severity of underlying ocular diseases found in these eyes