Celso Tello

Enhanced Depth Imaging Optical Coherence Tomography of Deep Optic Nerve Complex Structures in Glaucoma

OBJECTIVE To assess the usefulness of enhanced depth imaging (EDI) optical coherence tomography (OCT) for evaluating deep structures of the optic nerve complex (ONC; optic nerve head and peripapillary structures) in glaucoma. DESIGN Prospective, observational study. PARTICIPANTS Seventy-three established glaucoma patients (139 eyes) with a range of glaucomatous damage. METHODS Serial horizontal and vertical EDI OCT images of the ONC were obtained from both eyes of each participant. Deep ONC structures, including the lamina cribrosa (LC), short posterior ciliary artery (SPCA), central retinal artery (CRA), central retinal vein (CRV), peripapillary choroid and sclera, and subarachnoid space around the optic nerve, were investigated for their visibility and morphologic features. MAIN OUTCOME MEASURES Deep ONC structures identified in EDI OCT images. RESULTS Visual field mean deviation of 139 included eyes was -11.8 ± 8.6 dB (range, -28.70 to -2.01 dB). The anterior laminar surface was identified in all eyes in the central laminar area and in 91 (65%) eyes in the periphery beneath the neuroretinal and scleral rims or vascular structures. The LC pores with various shapes and sizes were visualized in 106 (76%) eyes, mainly in the central and temporal areas of the LC. Localized LC lesions seen on optic disc photographs were identified as focal LC defects (partial loss of LC tissue) in the EDI OCT images. The locations of the CRA and CRV were identified in all eyes. In the LC, the CRA maintained a straight shape with a consistent caliber, but the CRV (and tributaries) assumed a more irregular shape. The SPCAs, their branches through the emissary canals in the sclera, or both were visualized in 120 (86%) eyes. The subarachnoid space around the optic nerve was identified with varying degrees of clarity in 25 eyes (18%): 17 had high myopia and extensive parapapillary atrophy. Intrachoroidal cavitation or choroidal schisis, which had been unrecognized clinically, was identified in 2 eyes (1%) with high myopia. CONCLUSIONS Enhanced depth imaging OCT was able to visualize a wide variety of deep ONC structures in glaucoma patients and may be helpful in detecting, conceptualizing, and understanding basic and complicated in vivo anatomic and pathologic features of the ONC in glaucoma. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

The African descent and glaucoma evaluation study (ADAGES): Design and baseline data

OBJECTIVE To identify factors accounting for differences in glaucoma onset and rate of progression between individuals of African descent and European descent. DESIGN A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured. RESULTS Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79). CONCLUSIONS Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group. Trial Registration clinicaltrials.gov Identifier: NCT00221923.

β-Zone Parapapillary Atrophy and the Velocity of Glaucoma Progression

PURPOSE Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. DESIGN Retrospective, comparative study. PARTICIPANTS Two hundred forty-five patients from the New York Glaucoma Progression Study. METHODS Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. MAIN OUTCOME MEASURES The relationship between beta-zone PPA and the rate and risk of glaucoma progression. RESULTS Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (<525 microm) had a weak but significant correlation with presence of beta-zone PPA (kappa = 0.13). CONCLUSIONS Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance.

Initial Parafoveal Versus Peripheral Scotomas in Glaucoma: Risk Factors and Visual Field Characteristics

OBJECTIVE To assess risk factors for an initial parafoveal scotoma (IPFS) compared with an initial nasal step (INS) in glaucoma. DESIGN Retrospective, observational study. PARTICIPANTS Sixty-nine patients with glaucoma with an isolated IPFS and 53 patients with an isolated INS. METHODS On the basis of 2 reliable, consistent 24-2 Swedish interactive threshold algorithm standard visual fields (VFs), 2 groups of patients with glaucoma were studied: those with an IPFS in 1 hemifield (≥3 adjacent points with P<5% within the central 10 degrees of fixation, ≥1 point with P<1% lying at the innermost paracentral points, and no VF abnormality outside the central 10 degrees) and those with an INS in 1 hemifield (≥3 adjacent points with P<5% in the nasal periphery outside 10 degrees of fixation, the nasal-most point with P<1%, and no VF abnormality within the central 10 degrees). Clinical characteristics and systemic factors were recorded from charts and compared between the 2 groups. MAIN OUTCOME MEASURES Maximum untreated intraocular pressure (IOP), disc hemorrhage (DH) detection during follow-up, systemic risk factors, and VF mean deviation (MD) and pattern standard deviation (PSD). RESULTS Maximum untreated IOP (21.6±4.5 vs. 28.3±9.6 mmHg; P<0.001) was significantly lower, and frequency of DH detection (44% vs. 17%; P=0.001) and systemic risk factors (hypotension, migraine, Raynauds phenomenon, and sleep apnea; 16%, 23%, 24%, and 9% vs. 0%, 4%, 9%, and 0%; P=0.001, 0.002, 0.025, and 0.030, respectively) were significantly higher in patients with an IPFS than in patients with an INS. There were no significant differences in age, gender, family history of glaucoma, refractive error, central corneal thickness, and disc area between the 2 groups (all P>0.1). Mean deviation was similar between the 2 groups (P=0.346), but PSD was significantly greater in the IPFS group than in the INS group (P=0.043). CONCLUSIONS Eyes with an IPFS differ from those with an INS. These findings may help clinicians identify patients at higher risk of early central field loss.

In Vivo Evaluation of Focal Lamina Cribrosa Defects in Glaucoma

OBJECTIVES To assess focal lamina cribrosa (LC) defects in glaucoma using enhanced depth imaging optical coherence tomography and to investigate their spatial relationships with neuroretinal rim and visual field loss. METHODS Serial horizontal and vertical enhanced depth imaging optical coherence tomographic images of the optic nerve head were obtained from healthy subjects and those with glaucoma. Focal LC defects defined as anterior laminar surface irregularity (diameter, >100 μm;depth, >30 μm) that violates the normal smooth curvilinear contour were investigated regarding their configurations and locations. Spatial consistency was evaluated among focal LC defects, neuroretinal rim thinning/notching, and visual field defects. RESULTS Forty-six healthy subjects (92 eyes) and 31 subjects with glaucoma (45 eyes) were included. Ninety-eight focal LC defects representing various patterns and severity of laminar tissue loss were found in 34 eyes with glaucoma vs none in the healthy eyes. Seven of 11 eyes with glaucoma with no visible focal LC defect had a deeply excavated optic disc with poor LC visibility. Eleven focal LC defects presented clinically as an acquired pit of the optic nerve, and the others as neuroretinal rim thinning/notching. Focal LC defects preferably occurred in the inferior/inferotemporal far periphery of the LC including its insertion. Eyes with focal LC defects limited to the inferior half of the optic disc had greater sensitivity loss in the superior visual hemifield and vice versa. CONCLUSIONS Mechanisms of LC deformation in glaucoma include focal loss of laminar beams, which may cause an acquired pit of the optic nerve in extreme cases.Focal LC defects occur in tandem with neuroretinal rim and visual field loss.

Prevention of Blinking Alters Iris Configuration in Pigment Dispersion Syndrome and in Normal Eyes

PURPOSE To examine the effect of blinking on iris configuration and aqueous humor distribution between the posterior and anterior chambers in eyes with pigment dispersion syndrome compared with healthy eyes. METHODS High-resolution, anterior segment ultrasound biomicroscopy was performed on ten eyes of ten patients with untreated pigment dispersion syndrome and on ten control subjects. Patients were scanned continuously for 15 minutes or until the maximal change in iris configuration occurred. During this time, the eyelids were held open mechanically, and blinking was prevented. Eyes then were rescanned immediately after blinking. RESULTS Initial iris configuration was concave in all eyes with pigment dispersion syndrome, whereas in control eyes it was concave in four eyes, planar in four eyes, and convex in two eyes. Iridozonular contact occurred in eyes with pigment dispersion syndrome only. Iridolenticular contact was greater in eyes with pigment dispersion syndrome than in control eyes. Analysis of covariance controlling for age, sex, and refractive error showed pigment dispersion syndrome to be a significant predictor of increased iris concavity. During continuous scanning, the mean change in iris position, from most concave to most convex, and mean time to the maximal change in iris configuration were greater for eyes with pigment dispersion syndrome than in control eyes and were related to the degree of initial iris concavity only (analysis of covariance). In six eyes with pigment dispersion syndrome, the eye cup was removed, normal blinking was permitted, and the eye was rescanned. The iris resumed a concave configuration in all eyes. CONCLUSION Increased iris concavity in pigment dispersion syndrome appears to be related to increased iridolenticular contact. This creates an anatomic configuration that predisposes to reverse pupillary block. The accumulation of aqueous humor in the posterior chamber, when blinking is prevented, alters iris position in pigment dispersion syndrome and in healthy eyes and increases iridozonular and iridociliary-process distances while minimizing iridolenticular contact. Normal blinking appears to create transient vector forces which promote aqueous humor flow from the posterior to anterior chamber.

Ultrasound Biomicroscopy in Pseudophakic Malignant Glaucoma

BACKGROUND Malignant glaucoma (ciliary block glaucoma; aqueous misdirection glaucoma) is an incompletely understood, rare and serious complication of intraocular surgery. METHODS A woman with pseudophakic malignant glaucoma underwent successful neodymium: YAG (Nd:YAG) laser photodisruption of the anterior hyaloid face with resolution of the glaucoma. High-resolution ultrasound biomicroscopy was used to image the anterior segment and anterior chamber angle before and after laser surgery. RESULTS Ultrasound biomicroscopy provided cross-sectional images of the iris, posterior chamber intraocular lens (IOL), and ciliary body and their relative positions before and after resolution of the malignant glaucoma. Anterior rotation of the ciliary body and anterior chamber shallowing normalized after rupture of the anterior hyaloid face. CONCLUSION High-resolution ultrasound biomicroscopy provided images consistent with accepted concepts of the pathophysiology of this disease and offers great promise for the future elucidation of the anatomic mechanisms underlying various forms of glaucoma.

Spatially Consistent, Localized Visual Field Loss before and after Disc Hemorrhage

PURPOSE To evaluate the rate and location of visual field (VF) progression before and after detection of disc hemorrhage (DH). METHODS Disc photographs of consecutive patients with glaucoma with >or=5 SITA-Standard 24-2 VF in either eye were evaluated for the presence and location of DH. Exclusion criteria included disorders other than glaucoma likely to affect the VF and an insufficient number of VF test results to create a slope before or after DH detection. Automated pointwise linear regression was used to calculate global and localized rates of progression before and after DH. RESULTS One hundred sixty-eight DHs were identified in 122 patients (mean age, 68.9 +/- 11.2 years). The mean number of VF tests was 9.0 +/- 4.4, spanning a mean of 6.7 +/- 3.8 years. Mean global progression rates before and after DH were -0.6 +/- 0.8 and -1.0 +/- 1.2 dB/y, respectively (P = 0.01). The mean rate of progression points corresponding to the DH sector before and after detection were -2.02 +/- 1.0 and -3.7 +/- 3.6 dB/y, respectively (P < 0.01). All rates were significantly faster than in fellow, non-DH eyes (P < 0.05). The VF sector with the fastest progression rate predicted the location of the future DH in 85% of cases. After the detection of DH, the same VF sector maintained the fastest progression rate in almost all eyes (92%). CONCLUSIONS Spatially consistent, localized VF change occurred in regions of subsequent DH and continued to progress in the same regions at a faster rate. This finding suggests that rapid, localized disease progression predisposes to DH and that progressive VF loss continues because of the ongoing damage at or adjacent to this location.

Effect of a tight necktie on intraocular pressure

Aim: To evaluate the effect of a tight necktie on intraocular pressure (IOP) measurement using Goldmann applanation tonometry. Methods: 40 eyes of 20 normal subjects and 20 open angle glaucoma patients (all male) were enrolled. IOP was measured with an open shirt collar, 3 minutes after placing a tight necktie, and 3 minutes after loosening it. All measurements were made by the same examiner. Results: Mean IOP in normal subjects increased by 2.6 (SD 3.9) mm Hg (p=0.008, paired t test; range −3 to +14 mm Hg) and in glaucoma patients by 1.0 (1.8) mm Hg (p=0.02, paired t test; range −2 to +4.5 mm Hg). In normal subjects, IOP in 12 eyes was increased by ⩾2 mm Hg and in seven eyes by ⩾4 mm Hg. In glaucoma patients, IOP in six eyes was increased by ⩾2 mm Hg and in two eyes by ⩾4 mm Hg. Conclusion: A tight necktie increases IOP in both normal subjects and glaucoma patients and could affect the diagnosis and management of glaucoma.

Corneal hysteresis and visual field asymmetry in open angle glaucoma.

PURPOSE To investigate the association between corneal biomechanical parameters and asymmetric primary open angle glaucoma (POAG) using the Ocular Response Analyzer (ORA). METHODS In a prospective cross-sectional study, ORA parameters were measured in 117 POAG patients with asymmetric visual fields (VF). The asymmetry in VF was defined as a five point difference between the eyes using the Advanced Glaucoma Intervention Study (AGIS) scoring system. Subjects with previous intraocular or refractive surgery, ocular comorbidities and diabetes were excluded. RESULTS In worse eyes, mean AGIS scores were significantly higher (8.1 ± 4.3 vs. 1.0 ± 1.6; P < 0.001) and mean corneal hysteresis (CH) was significantly lower (8.2 ± 1.9 vs. 8.9 ± 1.9 mm Hg; P < 0.001). Median ORA-corrected intraocular pressure was higher in the worse eyes (IOP(cc), 17.4 mm Hg vs. 16.9 mm Hg; P < 0.001). Worse eyes had a slightly lower mean corneal resistance factor (P = 0.04) and more myopic mean spherical equivalent (P = 0.02). No difference was seen in the central corneal thickness (CCT; P = 0.63) and Goldmann applanation tonometry (GAT; P = 0.32). On multivariate analysis, only CH retained an association with the worse eye (odds ratio, 25.9; 95% confidence interval, 10.1-66.5). ROC curves showed that only CH and IOP(cc) had a discriminative ability for the eye with worse VF (AUC, 0.82 and 0.70, respectively). CONCLUSIONS Asymmetric POAG was associated with asymmetry in ORA parameters but not in CCT and GAT. Lower CH was associated with worse eyes independently of its effect on IOP measurement and had the best discriminability for the eye with the worse VF.