Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Objective assessment of visual acuity: a refined model for analyzing the sweep VEP.

PURPOSE: The aim of this study was to develop a simple and reliable method for the objective assessment of visual acuity by optimizing the stimulus used in commercially available systems and by improving the methods of evaluation using a nonlinear function, the modified Ricker model. METHODS: Subjective visual acuity in the normal subjects was measured with Snellen targets, best-corrected, and in some cases also uncorrected and with plus lenses (+ 1 D, + 2 D, + 3 D). In patients, subjective visual acuity was measured best-corrected using the Freiburg Visual Acuity Test. Sweep VEP recordings to 11 spatial frequencies, with check sizes in logarithmically equidistant steps (0.6, 0.9, 1.4, 2.1, 3.3, 4.9, 7.3, 10.4, 18.2, 24.4, and 36.5 cpd), were obtained from 56 healthy subjects aged between 17 and 69 years (mean 42.5 ± 15.3 SD years) and 20 patients with diseases of the lens (n = 6), retina (n = 8) or optic nerve (n = 6). The results were fit by a multiple linear regression (2nd-order polynomial) or a nonlinear regression (modified Ricker model) and parameters compared (limiting spatial frequency (sflimiting) and the spatial frequency of the vertex (sfvertex) of the parabola for the 2nd-order polynomial fitting, and the maximal spatial frequency (sfmax), and the spatial frequency where the amplitude is 2 dB higher than the level of noise (sfthreshold) for the modified Ricker model. RESULTS: Recording with 11 spatial frequencies allows a more accurate determination of acuities above 1.0 logMAR. Tuning curves fitted to the results show that compared to the normal 2nd-order polynomial analysis, the modified Ricker model is able to describe closely the amplitudes of the sweep VEP in relation to the spatial frequencies of the presented checkerboards. In patients with a visual acuity better than about 0.5 (decimal), the predicted acuities based on the different parameters show a good match of the predicted visual acuities based on the models established in healthy volunteers to the subjective visual acuities. However, for lower visual acuities, both models tend to overestimate the visual acuity (up to ~ 0.4 logMAR), especially in patients suffering from AMD. CONCLUSIONS: Both models, the 2nd-order polynomial and the modified Ricker model performed equally well in the prediction of the visual acuity based on the amplitudes recorded using the sweep VEP. However, the modified Ricker model does not require the exclusion of data points from the fit, as necessary when fitting the 2nd-order polynomial model making it more reliable and robust against outliers, and, in addition, provides a measure for the noise of the recorded results.

Sonographic Assessment of Optic Disc Cupping and its Diagnostic Performance in Glaucoma.

PURPOSE: The purpose of this study was to assess the optic cup diameter sonographically in glaucoma patients and in the normal population and correlate it with their photographic parameters to propose a cut-off value as a predictive index of glaucoma. METHODS: A total of 95/50 primary open-angle glaucoma and 87/44 control patients with clear media underwent visual field assessment, fundus photography, and B-scan ultrasound. Photographic vertical cup diameter (PVCD) of cases and controls were recorded after magnification correction using the Bengtsson formula. Sonographic vertical cup diameter (SVCD) was measured in the vertical transverse position. RESULTS: The mean SVCD was 1.13±0.23 mm in glaucoma and 0.72±0.25 mm in controls (P=0.001). The mean PVCD was 1.024±0.199 mm in glaucoma and 0.636±0.217 mm in controls (P=0.001). A strong correlation between PVCD and SVCD in both groups was found (correlation coefficient r=0.857; P=0.001; glaucoma and r=0.795; P=0.001; control). SVCD had a positive correlation with vertical cup disc ratio (r=0.675; P=0.001 in glaucoma patients) and (r=0.797; P=0.001 in controls) cup area (r=0.798; P=0.001; glaucoma) and (r=0.727, P=0.001; control) a negative correlation with vertical neuroretinal rim diameter (r=-0.5187; P=0.000; glaucoma patients) and (r=-0.699; P=0.001; controls). No correlation of SVCD was found with severity of field grade changes. The receiving operative curve analysis was performed, and Youden's optimal cut-off method was used to find a cut-off value for SVCD, which came out to be 1.06, with 65.3% (95% confidence interval, 54.8-74.7) sensitivity and 94.3% (95% confidence interval, 87.1-97.1) specificity. CONCLUSIONS: The sonographic evaluation of the optic cup is a reliable noninvasive procedure and a potentially useful tool in the assessment of nonviewable suspected glaucomatous cups.

Assessment of Glaucomatous Damage After Boston Keratoprosthesis Implantation Based on Digital Planimetric Quantification of Visual Fields and Optic Nerve Head Imaging.

PURPOSE: To investigate glaucomatous damage in Boston keratoprosthesis type I (KPro) patients through structural analysis of the optic nerve head and digital planimetric quantification of Goldmann visual fields, a novel method of monitoring perimetric changes in KPro patients. METHODS: Records of patients undergoing KPro implantation from 2007 to 2015 at a single institution were reviewed. Parameters related to glaucoma status and KPro outcomes were analyzed. RESULTS: Twenty-two eyes from 21 patients met inclusion criteria, with mean follow-up of 49.4 months (range 15-90). Mean results for the following parameters before KPro implantation and at last follow-up were (pre-KPro; at last follow-up): best-corrected visual acuity (2.07; 0.70 logMAR), number of glaucoma medications (1.14; 1.05), intraocular pressure (IOP) (18.4; 18.4 mm Hg), vertical cup-to-disc ratio (C/D) (0.48; 0.50), and horizontal C/D (0.52; 0.52). IOP-lowering procedures were performed pre-KPro (5/22), concurrently with KPro (10/22), post-KPro (6/22), or never (6/22). An increase in C/D ≥0.1 and loss of V4e isopter area >30% occurred in 22.7% and 12.5%, respectively. Development of post-KPro glaucoma, progression of preexisting or post-KPro glaucoma, and no glaucoma development as evidenced by an objective assessment of structural and functional parameters were seen in 2/22 (9.1%), 7/22 (31.8%), and 6/22 (27.3%) eyes, respectively. CONCLUSIONS: Clinicians should strive to vigilantly monitor for glaucoma despite the inherent difficulties in tonometry, optic nerve visualization and imaging, and visual field testing in KPro patients. Meticulous glaucoma surveillance with structural and functional testing combined with earlier IOP-lowering surgical intervention may result in decreased rates of glaucomatous vision loss in KPro patients.

The ganglion cell complex as an useful tool in glaucoma assessment.

Glaucoma is known as an optic neuropathy prone to progression that determines characteristic not only structural (loss of the ganglion cells as well as their axons) but also functional defects (visual field loss). Objective: To evaluate the possibility of applying ganglion cell complex analysis (GCC) in patients who associate ocular hypertension with tilted disc and marked peripapillary atrophy. Methods: In order to evaluate its components, GCC can be investigated using the Optical Coherence Tomography (OCT) revealing: ganglion cell layer (cells bodies), inner plexiform layer (dendrites and synapses), and nerve fiber layer (axons). Our study included 196 eyes divided into 3 groups: 52 diagnosed with primary open angle glaucoma (POAG), 63 with ocular hypertension (OH), and 81 healthy (normal) eyes (NE). All eyes were submitted to a complete ophthalmologic checkup that involved advanced optic nerve and GCC evaluation. Results: A positive statistically significant correlation was identified between the GCC thickness and the RNFL in all three categories taken into account: R=0,6, p<0,0001 for glaucoma group, R=0,66, p<0,0001 for OH group and R=0,46, p<0,0001 for normal group. Conclusions: GCC has been proved useful for the assessment of the retinal nerve fiber layer (RNFL) in eyes with OH that associate tilted disc or peripapillary atrophy where the optic disc edges might not be certainly determined by the OCT.

Methimazole-induced liver injury overshadowed by methylprednisolone pulse therapy: Case report.

RATIONALE: Treatment choices are limited, when deciding how to manage thyrotoxicosis and moderate to severe Graves ophthalmopathy (GO) with suspected optic nerve damage in patients with elevated liver transaminase levels. The situation become even more complicated, if methimazole induced hepatotoxicity is suspected and intravenous methylprednisolone is co-administrated. PATIENT CONCERNS: A 74-year-old woman presented with spontaneous retro-bulbar pain, eyelid swelling and inconstant diplopia. DIAGNOSES: Thyrotoxicosis and severe GO with suspected optic nerve damage and drug induced liver injury (DILI). INTERVENTIONS: Intravenous methylprednisolone pulse therapy was administered to treat GO and methimazole was continued for thyrotoxicosis. Dose of methimazole was reduced after exclusion of concurrent infection and active liver disease. OUTCOMES: The GO symptoms (eyelid swelling, sight loss, proptosis, retro-bulbar pain, diplopia) markedly decreased after the treatment course. Liver transaminases spontaneously returned to normal ranges and remained normal during the next 12 months until the Graves' disease until the treatment was completed. LESSONS: 1. The interaction of methimazole and methylprednisolone may result in DILI. 2. In a patient without concomitant liver diseases MP can be continued if the methimazole dose is reduced if no other treatment options are available.

Assessment of the retinal posterior pole in dominant optic atrophy by spectral-domain optical coherence tomography and microperimetry.

BACKGROUND: To assess posterior pole (PP) retinal structure in patients with genetically confirmed autosomal dominant optic atrophy (ADOA) using new spectral domain optical coherence tomography (SD-OCT) segmentation technology. To analyze retinal PP thickness in relation to retinal sensitivity data from microperimetry (MP) in ADOA patients. METHODS AND FINDINGS: This prospective cross-sectional study included 11 patients with ADOA and 11 age-matched healthy subjects. All participants underwent both a "Posterior Pole" and "peripapillary RNFL (pRNFL)" scanning protocol using SD-OCT. Functional mapping of the PP was also performed using MP. A customized program was implemented in order to achieve accurate superimposition of MP sensitivity map onto SD-OCT map. The thickness of the PP different retinal layers and pRNFL was obtained and measured for each eye. Mean retinal sensitivity values and fixation stability were obtained and compared between ADOA patients and healthy subjects. Correlation analysis was performed on a point-to-point basis to evaluate the association between mean thickness and retinal sensitivity of each retinal layer. Total retinal thickness (TRT), Retinal Nerve Fiber Layer (RNFL), Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL), Inner Nuclear Layer (INL) and Inner Retinal Layers (IRL) at the posterior pole as well as pRNFL were significantly thinner in ADOA patients (P < 0.0001). On the contrary, the Outer Plexiform Layer (OPL) and the Outer Nuclear Layer (ONL) were significantly thicker in the ADOA group (P < 0.001). No significant differences were found in Retinal Pigment Epithelium (RPE) and Outer Retinal Layers (ORL) thickness between ADOA and controls. The average PP retinal sensitivity was significantly reduced in ADOA patients compared with controls (P < 0.001), as measured by microperimeter Nidek MP-1 (MP1). Fixation stability was significantly worse in the ADOA group (P = 0.01). The most severe sensitivity defects in ADOA patients were found at the level of the papillo-macular bundle (PMB). CONCLUSIONS: Inner retinal layers showed pathological changes in ADOA patients. In addition, the whole retinal PP (not only the PMB) was significantly altered in ADOA, both in terms of retinal thickness and sensitivity.

Assessment of Optic Pathway Structure and Function in Patients With Compression of the Optic Chiasm: A Correlation With Optical Coherence Tomography.

PURPOSE: The purpose of this study was to investigate correlations between retinal fiber thickness measured by optical coherence tomography (OCT) and anterograde functional and structural differences in the optic pathway of patients with compression of the optic chiasm. Our hypothesis was that loss of visual acuity caused by chronic compressive pathologies may lead to an irreversible decline in vision because of permanent neurodegeneration of the optic radiations and visual cortex. METHODS: Quantitative OCT, functional magnetic resonance imaging (MRI) and diffusion tensor MRI measurements were made in 17 patients being surgically treated for chiasmal compression. RESULTS: In our study we found that surgically irreversible visual field defects and reduced retinal nerve fiber layer thickness were significantly associated with lower fractional diffusion anisotropy and higher diffusivities in optic radiations and less functional MRI activation in the visual cortex. CONCLUSIONS: Damage to the retinal nerve fiber layer is associated with downstream structural and functional degradation of the optic pathway. This may be related to trans-synaptic degeneration and the fact that these factors are important potential imaging biomarkers for predicting visual recovery after surgical decompression.

The diagnosis and assessment of visual function in Singaporean children with electrophysiology: 10-year results.

PURPOSE: To study the clinical use and efficacy of electrophysiology in children. METHODS: This was a retrospective review of all children aged <16 years, who were referred to the Visual Electrophysiology Laboratory at the Singapore National Eye Center between 2003 and 2013. RESULTS: A total of 586 children, median age 8 years (range 0.15-16), were referred for a variety of reasons including investigation of poor vision (40 %), suspected retinal disease or optic nerve/cortical dysfunction (17 %), nystagmus (13 %) and screening or monitoring of a variety of ocular or neurological conditions (12 %). The number of children with vision 6/15 or worse was 418 (71 %), and 103 (18 %) had vision 6/120 or worse in at least one eye. The most common pathology noted was retinal dystrophy or dysfunction (41 %) or optic nerve/cortical dysfunction (12 %). In 30 %, visual electrophysiology was within normal limits, and in 6 %, a conclusive diagnosis could not be obtained. CONCLUSION: Electrophysiology testing played an important role in the assessment of children and added to the clinical management of the patient.

Biomechanical assessment in models of glaucomatous optic neuropathy.

The biomechanical environment within the eye is of interest in both the regulation of intraocular pressure and the loss of retinal ganglion cell axons in glaucomatous optic neuropathy. Unfortunately, this environment is complex and difficult to determine. Here we provide a brief introduction to basic concepts of mechanics (stress, strain, constitutive relationships) as applied to the eye, and then describe a variety of experimental and computational approaches used to study ocular biomechanics. These include finite element modeling, direct experimental measurements of tissue displacements using optical and other techniques, direct experimental measurement of tissue microstructure, and combinations thereof. Thanks to notable technical and conceptual advances in all of these areas, we are slowly gaining a better understanding of how tissue biomechanical properties in both the anterior and posterior segments may influence the development of, and risk for, glaucomatous optic neuropathy. Although many challenging research questions remain unanswered, the potential of this body of work is exciting; projects underway include the coupling of clinical imaging with biomechanical modeling to create new diagnostic tools, development of IOP control strategies based on improved understanding the mechanobiology of the outflow tract, and attempts to develop novel biomechanically-based therapeutic strategies for preservation of vision in glaucoma.

Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma.

The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell (RGC) degeneration, the main features of which are iris pigment dispersion (IPD) and iris stromal atrophy (ISA). These animals also experience glaucomatous changes, including an increase in intraocular pressure (IOP) beginning at about 9-12 months of age and sectorial RGC death in the retina. The aim of this study was to determine the onset of functional changes exhibited by DBA/2J mice in the inner retina. This was performed by means of electroretinographic recordings (scotopic threshold response, STR) and their correlation with morphological changes (loss of RGCs). To this end, we recorded the scotopic threshold response in control C57BL/6J and in DBA/2J mice at different ages. The RGCs, in both DBA/2J and C57BL/6J animals, were identified at 15 months of age by retrograde tracing with an analogue of fluorogold, hydroxystilbamidine methanesulfonate (OHSt), applied on the superior colliculi. Whole mount retinas were processed to quantify the population of RGCs identified by fluorogold tracing and Brn3a immunodetection, and were counted using image analysis software; an isodensity contour plot was generated for each retina. DBA/2J mice showed a significant reduction in the positive STR (pSTR) amplitudes at 12 months of age, as compared to control C57BL/6J mice of the same age. The pSTR mean amplitude decreased to approximately 27.82% of the values recorded in control mice (p = 0.0058). STR responses decreased in both strains as a result of the natural process of aging, but the decrease was more pronounced in DBA/2J mice. Furthermore, quantification of the total number of RGCs identified by OHSt and Brn3a expression showed a reduced population of RGCs in DBA/2J mice as compared to control mice. Regression analysis revealed significant correlations between the decrease in pSTR and a non-homogeneous reduction in the number of RGCs throughout the retina. Our results indicate the existence of a correlation between retinal function impairment and RGC loss. This functional and morphological analysis allows a reliable assessment of the progression of the disease.

An adherence based cost-consequence model comparing bimatoprost 0.01% to bimatoprost 0.03%.

OBJECTIVES: Estimate the long-term direct medical costs and clinical consequences of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the treatment of glaucoma. METHODS: A cost-consequence model was constructed from the perspective of a US healthcare payer. The model structure included three adherence levels (high, moderate, low) and four mean deviation (MD) defined health states (mild, moderate, severe glaucoma, blindness) for each adherence level. Clinical efficacy in terms of IOP reduction was obtained from the randomized controlled trial comparing bimatoprost 0.01% with bimatoprost 0.03%. Medication adherence was based on observed 12 month rates from an analysis of a nationally representative pharmacy claims database. Patients with high, moderate and low adherence were assumed to receive 100%, 50% and 0% of the IOP reduction observed in the clinical trial, respectively. Each 1 mmHg reduction in IOP was assumed to result in a 10% reduction in the risk of glaucoma progression. Worse glaucoma severity health states were associated with higher medical resource costs. Outcome measures were total costs, proportion of patients who progress and who become blind, and years of blindness. Deterministic sensitivity analyses were performed on uncertain model parameters. RESULTS: The percentage of patients progressing, becoming blind, and the time spent blind slightly favored bimatoprost 0.01%. Improved adherence with bimatoprost 0.01% led to higher costs in the first 2 years; however, starting in year 3 bimatoprost 0.01% became less costly compared to bimatoprost 0.03% with a total reduction in costs reaching US$3433 over a lifetime time horizon. Deterministic sensitivity analyses demonstrated that results were robust, with the majority of analyses favoring bimatoprost 0.01%. Application of 1 year adherence and efficacy over the long term are limitations. CONCLUSIONS: Modeling the effect of greater medication adherence with bimatoprost 0.01% compared with bimatoprost 0.03% suggests that differences may result in improved economic and patient outcomes.

[New insights into the pathogenesis of glaucomatous optic neuropathy and refinement of the objective assessment of its functional damage].

Glaucomatous optic neuropathy is a primary pathological condition responsible for visual dysfunction due to glaucoma. However, how intraocular pressure and other risk factors lead to glaucomatous optic neuropathy is not fully understood. Given that static or kinetic visual field tests for evaluating visual dysfunction in glaucomatous optic neuropathy are a subjective assessments based on a psychophysical principle, the development of a tool for objective assessment of the visual field is needed. In this study, we attempt to elucidate the pathophysiology of glaucomatous optic neuropathy and to refine a modality for the objective assessment of the visual dysfunction due to it. Aquaporin (AQP) water channels are located primarily in the plasma membrane. These proteins form either a homo- or hetero-tetramer and allow water to cross the plasma membrane bi-directionally. The transmembrane water movement through AQPs is critically involved in the maintenance of normal neuronal activity. Among the 13 isoforms indentified so far, AQP-4 is known to be expressed in the retrobulbar portion of the optic nerve. However, the optic nerve head, the primary pathological site of glaucomatous optic neuropathy, reportedly does not express AQP-4. We found that in control rats, astrocytes throughout the optic nerve express AQP-9. The chronic elevation of intraocular pressure due to cauterization of three episcleral veins substantially reduced both gene expression and immunoreactivity of AQP-9, whereas it did not change the AQP-4 gene or protein expression in the retrobulbar portion of the optic nerve. These findings are implicated in the chronic elevation of intraocular pressure in astrocytes. Similar findings were also observed in the eyes of a monkey with angle-laser-induced ocular hypertension and of a human with primary open-angle glaucoma. AQP-9 was also expressed in the cell bodies of retinal ganglion cells in control rats and its expression was significantly reduced in the eyes of rats with ocular hypertension. Recently, the astrocyte-to-neuron lactate shuttle hypothesis has been proposed. This hypothesis suggests that lactate generated by glucose during glycolysis in astrocytes is used by neurons as an energy substrate. Given that AQP-9 belongs to an aquaglyceroporin subfamily and allows solutes other than water (e.g., lactate) to cross the plasma membrane, chronic ocular hypertension may perturb this physiological passage of lactate. Thus, lactate as the energy substrate may be unable to be transported from astrocytes to retinal ganglion cells at the cell bodies and axons due to the reduction of AQP-9 expression by astrocytes at the optic nerve head and retinal ganglion cells. The multifocal visual evoked potential (mfVEP) is an objective visual field test, which enables the recording of cortical potential corresponding to 60 local retinal areas simultaneously. Evidence is accumulating that the signal-to-noise ratio (SNR) has been enhanced by recording mfVEPs from multiple channels at the same time. However, previous studies evaluated the mfVEPs mostly in Caucasians. It has not yet been proven whether this strategy is applicable to Japanese people who have a skull frame that may be different from that of Caucasians. We calculated the relative position of the calcarine landmark for electrode placement during the mfVEP recording, from brain MRI images of 200 individuals, which were found to be 1 cm lower than those reported in Caucasians with a statistical significance. Then, we recorded mfVEPs from 110 normal controls using three channels and conducted receiver-operating characteristic (ROC) curve analysis of the overlap of SNR distribution at signal and noise windows. We found that a combination of one horizontal channel straddling the inion with either one of the two perpendicular vertical channels yielded the largest area under the ROC curve (AUC). Next, we showed that the SNR-AUC exhibited a similar diagnostic performance to, and a significant correlation with, a total deviation of the Humphrey visual field in 56 eyes with mild to moderate glaucomatous damage, which exhibited a mean deviation of -15 dB or less, and in 62 control eyes. In contrast, a topographical agreement in defining abnormal locations based on probability plots between the Humphrey visual field and mfVEP testing was moderate. The SNR-AUC may be used as a global index, analogous to the mean deviation of the Humphrey visual field, to quantify diffuse functional loss due to glaucomatous optic neuropathy, in contrast to the previously proposed cluster analysis of the mfVEP probability plots, which is a strategy more suitable to diagnosing local sensitivity loss.

Incorporating risk factors to improve the assessment of rates of glaucomatous progression.

PURPOSE: To present and evaluate a new method of integrating risk factors into the analysis of rates of visual field progression in glaucoma. METHODS: The study included 352 eyes of 250 glaucoma patients followed up for an average of 8.1 ± 3.5 years. Slopes of change over time were evaluated by the mean deviation (MD) from standard automated perimetry. For each eye, the follow-up time was divided into two equal periods: the first half was used to obtain the slopes of change and the second period was used to test the predictions. Slopes of change were calculated with two methods: the conventional approach of ordinary least squares (OLS) linear regression and a Bayesian regression model incorporating information on risk factors and presence of progressive optic disc damage on stereophotographs. The mean square error (MSE) of the predictions was used to compare the predictive performance of the different methods. RESULTS: Higher mean IOP, thinner central corneal thickness (CCT), and presence of progressive optic disc damage were associated with faster rates of MD change. Incorporation of risk factor information into the calculation of individual slopes of MD change with the Bayesian method resulted in better prediction of future MD values than with the OLS method (MSE: 4.31 vs. 8.03, respectively; P < 0.001). CONCLUSIONS: A Bayesian regression model incorporating structural and risk factor information into the estimation of glaucomatous visual field progression resulted in more accurate and precise estimates of slopes of functional change than the conventional method of OLS regression. (ClinicalTrials.gov number, NCT00221897.).

Assessment of corneal biomechanical properties in normal tension glaucoma and comparison with open-angle glaucoma, ocular hypertension, and normal eyes.

PURPOSE: To assess the biomechanical properties of corneas in patients with normal tension glaucoma (NTG) and to compare them with those of patients with primary open-angle glaucoma (POAG), ocular hypertension (OHT), and normal controls (N). METHODS: Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann intraocular pressure (IOPg), and corneal compensated IOP (IOPcc) were obtained using an ocular response analyzer for 28 eyes in 14 patients with NTG, 75 eyes in 38 patients with chronic POAG, 53 eyes of 27 patients with OHT, and 44 eyes of 22 N controls. IOP using Goldmann applanation tonometry (IOPGA) and ultrasonic central corneal thickness (CCT) were also measured for each eye. Analysis of variance test was used for statistical analysis. RESULTS: CH was significantly lower in the NTG group (9.88±2.02 mm Hg) compared with the N group (11.05±1.53 mm Hg; P<0.01). CRF was significantly lower in the NTG group (9.5±1.89 mm Hg) compared with the POAG group (11.15±2.35 mm Hg; P<0.01) and to the N group (11.00±1.75 mm Hg; P<0.01). CCT was not considered significantly different between the 4 groups. However, IOPcc was found to be significantly lower in NTG group compared with the POAG group and OHT group (P<0.001). CONCLUSION: NTG was associated with significantly lower CRF than chronic POAG and N patients. CH and CRF could be a useful tool in early diagnosis of NTG.

Assessment of linear-scale indices for perimetry in terms of progression in early glaucoma.

Currently, global indices that summarize the visual field combine sensitivities on a logarithmic (decibel) scale. Recent structure-function models for glaucoma suggest that contrast sensitivity should be converted to a linear scale before averaging across visual field locations, to better relate sensitivity with the number of surviving retinal ganglion cells (RGCs). New indices designed to represent the number of RGCs already lost are described. At least one was found to be a significantly better predictor of subsequent rate of change than traditional Mean Deviation (p=0.014) in participants with glaucomatous optic neuropathy. Issues concerning the creation of optimal global indices are discussed.

[Assessment of a patient with optic neuropathy]. / Evaluarea pacientului cu neuropatie optica.

Optic neuropathy (ON) is defined as the reduction of vision due to inflammatory lesion of the optic nerve. The patient with ON has to be evaluated clinically but also with complex techniques (magnetic resonance imaging, visual evoked potentials, cerebrospinal fluid examination) because ON could be the presenting symptom in multiple sclerosis patients. Corticosteroids should be administrated intravenous and the patient should be followed by the neurologist in order to signal the appearance of new neurological signs.

Determinants of agreement between the confocal scanning laser tomograph and standardized assessment of glaucomatous progression.

PURPOSE: To estimate the agreement of confocal scanning laser tomograph (CSLT), topographic change analysis (TCA) with assessment of stereophotographs, and standard automated perimetry (SAP) for detecting glaucomatous progression and to identify factors associated with agreement between methods. DESIGN: Observational cohort study. PARTICIPANTS: We included 246 eyes of 167 glaucoma patients, glaucoma suspects, and ocular hypertensives. METHODS: We included CSLT series (n ≥ 4 tests; mean follow-up, 4 years), stereophotographs, and SAP results in the analysis. The number of progressors by guided progression analysis (GPA, "likely progression"), progressors by masked stereophotographs assessment and progressors by TCA as determined for 3 parameters related to the number of progressed superpixels within the disc margin was determined. Agreement between progression by each TCA parameter, stereophotographs and GPA was assessed using the Kappa test. Analysis of variance with post hoc analysis was applied to identify baseline factors including image quality (standard deviation of the mean topography), disc size and disease severity (pattern standard deviation [PSD] and cup area) associated with agreement/nonagreement between methods. MAIN OUTCOME MEASURES: Agreement in assessing glaucomatous progression between the methods including factors associated with agreement/nonagreement between methods. RESULTS: Agreement between progression by TCA and progression by stereophotographs and/or GPA was generally poor regardless of the TCA parameter and specificity cutoffs applied. For the parameters with the strongest agreement, cluster size in disc (CSIZE(disc)) and cluster area in disc (CAREA(disc)), kappa values were 0.16 (63.9%, agreement on 134 nonprogressing eyes and 23 progressing eyes) and 0.15 (64.1%, agreement on 135 nonprogressing eyes and 22 progressing eyes) at 99% cutoff. Most of the factors evaluated were not significantly associated with agreement/nonagreement between methods (all P > 0.07). However, SAP PSD was greater in the progressors by stereophotography only group compared with the progressors by TCA only group (5.8 ± 4.7 and 2.6 ± 2.2, respectively [P = 0.003] for CSIZE(disc) at 95% specificity and 5.4 ± 4.6 and 2.5 ± 2.3, respectively [P = 0.002] for CAREA(disc) at 99% specificity). CONCLUSIONS: Agreement for detection of longitudinal changes between TCA, stereophotography, and SAP GPA is poor. Progressors by stereophotography only tended to have more advanced disease at baseline than progressors by TCA only.

Electrodiagnostic assessment in optic nerve disease.

PURPOSE OF REVIEW: Complementary electrophysiological techniques can be useful in detecting and localizing dysfunction within the visual pathway. Recent developments are outlined in the context of neuro-ophthalmology. RECENT FINDINGS: The relationship between nerve fibre layer anatomy and the pattern visual evoked potential has been addressed, correlating axonal loss with visual pathway dysfunction. Longitudinal assessment of multiple sclerosis patients has defined parameters affecting the utility of the pattern visual evoked potential as an outcome measure in potential treatment trials. In optic nerve tumours, the pattern visual evoked potential may help identify and monitor the disorder. The pattern electroretinogram assesses retinal ganglion cell function and can identify macular dysfunction, possibly mimicking optic nerve disease clinically. The spatial extent of macular dysfunction can be assessed using the multifocal electroretinogram. Objective visual evoked potential assessment of visual acuity can be important in the management of nonorganic visual loss. The multifocal visual evoked potential is a relatively new technique that is attracting increasing research interest, particularly as a measure of visual field loss, but has yet to be established as a reliable diagnostic tool. SUMMARY: Electrophysiology, combined with clinical and imaging investigations, is a powerful diagnostic and monitoring tool. Macular dysfunction can mimic optic nerve disease in the absence of fundus abnormality.