Daniel Su

Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen

OBJECTIVE To assess the value of enhanced depth imaging optical coherence tomography (EDI OCT) in diagnosing and evaluating optic nerve head drusen (ONHD) compared with conventional diagnostic methods. DESIGN Prospective, comparative, cross-sectional study. PARTICIPANTS Thirty-four patients with clinically visible or suspected ONHD in either eye based on dilated optic disc examination or optic disc stereophotography and without ocular comorbidity. METHODS Spectral-domain OCT of the optic nerve head in both conventional (non-EDI) and EDI modes, ultrasound B-scan, and standard automated perimetry were performed on both eyes of all participants. MAIN OUTCOME MEASURES Detection and findings of ONHD between EDI OCT and conventional diagnostic methods. RESULTS Sixty-eight eyes were clinically classified into 3 groups: 32 eyes with definite ONHD, 25 eyes with suspected ONHD, and 11 normal-appearing fellow eyes. In the definite ONHD group, EDI OCT, non-EDI OCT, and ultrasound B-scan were positive for ONHD in all eyes and visual field (VF) was abnormal in 24 eyes. In the suspected ONHD group, EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were positive in 17, 14, 7, and 3 eyes, respectively; 8 eyes had no evidence of ONHD in any of the tests. In normal-appearing fellow eyes, EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were positive in 3, 1, 1, and 0 eyes, respectively; 4 eyes had no evidence of ONHD in any of the tests. Enhanced depth imaging OCT had a significantly higher ONHD detection rate than ultrasound B-scan in all eyes (52/68 eyes vs. 40/68 eyes; P<0.001), in eyes with clinically suspected ONHD or normal-appearing fellow eyes (20/36 eyes vs. 8/36 eyes; P<0.001), and in eyes with clinically suspected ONHD (17/25 eyes vs. 7/25 eyes; P = 0.002). Enhanced depth imaging OCT-detected ONHD appeared as signal-poor regions surrounded by short, hyper-reflective bands or isolated/clustered hyper-reflective bands without a signal-poor core. In non-EDI OCT, posterior surfaces of the ONHD and deep-seated hyper-reflective bands were invisible or less clear than in EDI OCT. CONCLUSIONS Enhanced depth imaging OCT detects lesions likely representing ONHD more often and better assesses their shape and structure than conventional tests.

Focal Lamina Cribrosa Defects Associated With Glaucomatous Rim Thinning and Acquired Pits

IMPORTANCE Considering the potential clinical importance of focal lamina cribrosa (LC) defects as a characteristic structural feature in glaucoma and a risk factor for glaucomatous visual field progression, it may be helpful to know the structure of focal LC defects and the spatial relationship between them and glaucomatous optic disc changes such as neuroretinal rim thinning/notching and acquired pits of the optic nerve (APON). OBJECTIVE To investigate structural and spatial relationships between focal LC defects and glaucomatous neuroretinal rim thinning/notching and APON. DESIGN In a cross-sectional analysis of data from an ongoing, prospective, longitudinal study, serial enhanced-depth imaging (EDI) optical coherence tomographic (OCT) images of the optic nerve head were obtained from patients with glaucoma and reviewed for focal LC defects (laminar holes or disinsertions). Anterior laminar insertion points and edges of laminar holes or disinsertions were marked in EDI-OCT images, reconstructed 3-dimensionally, and superimposed on optic disc photographs. SETTING A glaucoma referral practice. PARTICIPANTS Two hundred thirty-nine eyes (120 patients) were examined. Fifty-four eyes were excluded because of an incomplete horizontal or vertical set of serial EDI-OCT images or poor-quality EDI-OCT images owing to media opacity, irregular tear film, or poor patient cooperation. Among the remaining 185 eyes, 40 (from 31 patients) had laminar holes or disinsertions and were included for analysis. MAIN OUTCOME MEASURES Presence, extent, and location of laminar holes or disinsertions. RESULTS Among 185 eyes, 11 laminar holes and 36 laminar disinsertions were found in 40 eyes. Superimposed images of the 3-dimensionally reconstructed focal LC defects and disc photographs showed that the outline of the LC defect corresponded almost precisely to that of clinical APON for 6 laminar holes and that the LC defect was much larger than and enclosed APON for 10 laminar disinsertions. The remaining 5 laminar holes and 26 laminar disinsertions corresponded to focal neuroretinal rim loss, with no evidence of APON in disc photographs. CONCLUSIONS AND RELEVANCE Focal LC defects (laminar holes or disinsertions) are associated with neuroretinal rim loss and APON. The extent of LC defects can be visualized more effectively on EDI-OCT images than by clinical examination.

Factors Associated With Focal Lamina Cribrosa Defects in Glaucoma

PURPOSE To assess factors associated with focal lamina cribrosa (LC) defects in glaucoma. METHODS Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head were obtained from glaucoma patients. EDI OCT scans were reviewed for focal LC defects (laminar holes or disinsertions). Evaluated clinical factors included age, central corneal thickness, visual field (VF) mean deviation (MD), exfoliation syndrome, normal-tension glaucoma (NTG), disc hemorrhage, and intraocular pressure (IOP) during past follow-up. RESULTS One hundred forty-eight glaucomatous eyes (148 patients; mean age, 68 ± 12 years; mean VF MD, -11.63 ± 6.96 dB) were included. Sixty-seven (45%) eyes had focal LC defects and 81 (55%) did not. Eyes with focal LC defects had a higher prevalence of both disc hemorrhage (25% vs. 6%) and NTG (33% vs. 9%) and worse VF MD (-14.12 vs. -9.58 dB) than those without focal LC defects (P = 0.002, P < 0.001, and P < 0.001, respectively). In the multivariate logistic regression analysis, higher frequency of disc hemorrhage detection (odds ratio [OR], 3.63; P = 0.032), a diagnosis of NTG (OR, 4.23; P = 0.005), and worse VF MD (OR, 1.11; P < 0.001) were significant factors associated with the presence of focal LC defects. Disc hemorrhage developed in the same half of the disc as the largest or the second largest focal LC defect in 15 of 17 eyes (88.2%). CONCLUSIONS Disc hemorrhage, a diagnosis of NTG, and more advanced glaucoma status are associated with focal LC defects. Future studies are needed to elucidate the cause-and-effect relationships between focal LC defects and these factors.

Effect of Focal Lamina Cribrosa Defect on Glaucomatous Visual Field Progression

OBJECTIVE To evaluate the association between focal, structural defects of the lamina cribrosa (LC) and glaucomatous visual field (VF) progression. DESIGN Retrospective, observational study. PARTICIPANTS A total of 169 patients with glaucoma (169 eyes) with a range of glaucomatous damage. METHODS Serial horizontal and vertical enhanced-depth imaging optical coherence tomography (EDI OCT) B-scans of the optic nerve head were obtained from patients with glaucoma with 5 or more prior Humphrey 24-2 VFs (Carl Zeiss Meditec, Inc, Dublin, CA). The EDI OCT scans were reviewed for the presence of focal LC defects (laminar holes or disinsertions with a diameter >100 μm). The VF progression was defined as having ≥ 2 significantly progressing test points (with a slope calculated using pointwise linear regression [PLR], worse than -1.0 dB/year at P<0.01). Age, intraocular pressure (IOP), baseline VF mean deviation (MD), disc hemorrhage, and central corneal thickness (CCT) were recorded. MAIN OUTCOME MEASURES The relationship between focal LC defects and the rate and risk of VF progression. RESULTS Mean age and VF MD at the time of EDI OCT were 69 ± 12 years and -11.49 ± 6.87 dB, respectively. Sixty eyes (36%) progressed according to PLR criteria. Progression was more common in eyes with, rather than without, focal LC defects (38/81 eyes [47%] vs. 22/88 eyes [25%], P = 0.003). Among the evaluated parameters, the presence of focal LC defects, disc hemorrhage, higher mean follow-up IOP, greater number of VFs, and longer follow-up period were significantly associated with VF progression in the multivariable analyses (odds ratios, 2.90, 4.66, 1.22, 1.25, and 1.27, respectively; P = 0.010, P = 0.002, P = 0.002, P<0.001, and P<0.001, respectively). The mean global progression rate was significantly faster in the group with focal LC defect than in the group with no focal LC defect (-0.54 ± 0.99 dB/year vs. -0.28 ± 0.52 dB/year; P = 0.031). Among the 60 progressing eyes, despite no significant difference in the mean number of progressing VF points per eye (6.7 ± 7.0 vs. 6.5 ± 4.4; P = 0.899), the mean localized progression rate was significantly faster in the eyes with focal LC defects than in the eyes with no focal LC defects (-2.85 ± 1.85 dB/year vs. -1.75 ± 0.56 dB/year; P = 0.009). CONCLUSIONS Focal LC defects are strongly associated with glaucomatous VF progression, and eyes with focal LC defects tend to progress faster than those without.

Parafoveal scotoma progression in glaucoma: humphrey 10-2 versus 24-2 visual field analysis.

OBJECTIVE To compare the performance of 10-2 versus 24-2 visual fields (VFs) in detecting progression of initial parafoveal scotoma (IPFS) in glaucomatous eyes. DESIGN Retrospective, observational study. PARTICIPANTS Glaucoma patients with the following criteria: (1) an IPFS (≥ 3 adjacent points with P<0.05 within the central 10° degrees of fixation, 1 point or more with P<0.01 lying at the innermost paracentral points, and no scotoma outside the central 10°) in either hemifield based on 2 reliable Humphrey 24-2 Swedish interactive threshold algorithm standard VFs, and (2) 5 or more 10-2 and 24-2 VFs. METHODS Based on threshold map sensitivities, VF progression, defined as having 1 or more significantly progressing point(s) with a slope of sensitivity of less than -1.0 dB/year at P<0.01, was evaluated using pointwise linear regression. MAIN OUTCOME MEASURES The number of progressing eyes in 10-2 and 24-2 VF analyses. RESULTS Fifty eyes (50 patients) were included (mean age ± standard deviation, 62 ± 9 years). Mean follow-up period (5.7 vs. 5.6 years) and number of VFs (7.6 vs. 7.8) were similar between 10-2 and 24-2 analyses (all P>0.3). Significantly more progressing eyes were detected in 10-2 than in 24-2 analyses (24 vs. 11 eyes; P = 0.007). This difference became greater within the central 10° (24 vs. 4 eyes; P<0.001). Four of the 11 progressing eyes in 24-2 analysis were missed in 10-2 analysis, whereas 17 of the 24 progressing eyes in 10-2 analysis were missed in 24-2 analysis. The 4 progressing eyes missed in 10-2 analysis had progressing point(s) only outside the central 10° in 24-2 analysis. The other 3 eyes with progressing point(s) only outside the central 10° in 24-2 analysis were detected as progressing in 10-2 analysis. Similar results were obtained when more stringent criteria (at least 2 significantly progressing points within the same hemifield) were used for VF progression. CONCLUSIONS The 10-2 VF detects more progressing eyes than the 24-2 VF in glaucoma patients with IPFS, suggesting that closer surveillance of the central VF using testing algorithms with closely spaced grids is warranted in eyes with parafoveal scotomas. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Progression Pattern of Initial Parafoveal Scotomas in Glaucoma

OBJECTIVE To characterize the progression pattern of initial parafoveal scotomas (IPFSs) using cross-sectional and longitudinal 10-2 visual field (VF) data. DESIGN Retrospective, observational study. PARTICIPANTS Glaucoma patients with an IPFS in either hemifield based on 2 reliable 24-2 Swedish interactive threshold algorithm standard VFs (≥3 adjacent points with P<0.05 within the central 10° of fixation, 1 point or more with P<0.01 lying at the innermost paracentral points, and no scotoma outside the central 10°) and at least 2 10-2 VFs (first and last VFs 1 year or more apart). METHODS To simulate a cohort with an extended follow-up, eyes with an IPFS were divided into subgroups based on the severity of glaucoma using their 10-2 VF pattern standard deviation (PSD). Cross-sectional data were used to create an average pattern deviation map that was generated by averaging pattern deviation map values of 10-2 VF point-by-point within each subgroup. Longitudinal data (eyes with 5 or more 10-2 VFs) was used to perform pointwise linear regression analysis of pattern deviation values. Patterns of IPFS progression were identified from these cross-sectional and longitudinal assessments. MAIN OUTCOME MEASURES Average pattern deviation maps (cross-sectional) and maps of progression rates (longitudinal) in different disease severity subgroups. RESULTS Eighty eyes (80 patients) and 40 eyes (40 patients) with an IPFS were included for cross-sectional and longitudinal analyses, respectively. The mean age ± standard deviation, 24-2 VF mean deviation, and 24-2 VF PSD for all eyes were 63±10 years, -3.27±2.18 dB, and 5.46±2.40 dB, respectively. Based on maps generated in both cross-sectional and longitudinal analyses, IPFS in the superior hemifield had an arcuate pattern initially that later deepened approximately 3° to 5° above fixation. The scotoma then elongated toward the physiologic blind spot and spread toward the nasal periphery, sparing the area corresponding to the papillomacular bundle. The IPFS in the inferior hemifield had a similar pattern, but was slightly farther from fixation. CONCLUSIONS Superior and inferior IPFS have a similar characteristic pattern of progression, although the latter tend to be farther from fixation. Understanding these patterns should help in the management of such patients and in improving VF testing algorithms.

Anti-VEGF therapy for the treatment of glaucoma: a focus on ranibizumab and bevacizumab

Introduction: Anti-VEGF therapy has been widely used in the treatment of ocular neovascular diseases. Because of their anti-angiogenic and anti-fibrotic properties, anti-VEGF antibodies such as bevacizumab and ranibizumab have emerged as an adjunctive treatment modality in glaucoma to improve success of conventional treatments. Areas covered: Ranibizumab is an anti-VEGF-A antigen binding fragment currently indicated in neovascular age-related macular degeneration as well as macular edema following retinal vein occlusion. Several off-label uses include the treatment of neovascular glaucoma to regress/suppress iris and iridocorneal angle neovascularization and the modulation of wound healing after glaucoma filtration surgery. Bevacizumab is a full-length anti-VEGF antibody, which is also being used in aforementioned eye conditions off-label. An overview of these anti-VEGF antibodies and the results of preclinical and clinical studies regarding their use in the treatment of glaucoma are presented. Expert opinion: Early studies on the utility of both bevacizumab and ranibizumab in neovascular glaucoma and filtration surgery reported promising results. However, a large-scale randomized clinical trial as well as comparative studies between the two anti-VEGF antibodies are currently lacking. A single dose of ranibizumab costs approximately 40 times as much as a single dose of bevacizumab. Clinicians should take this into account, in addition to their differences in the efficacy and safety, when treating patients.

Assessment of patient perception of glaucomatous visual field loss and its association with disease severity using Amsler grid

Purpose To investigate patients’ perception of glaucomatous VF loss and its association with glaucoma severity using the Amsler grid test. Methods In this prospective cross-sectional study, glaucoma patients with abnormal 10–2 Humphrey Swedish Interactive Threshold Algorithm-standard VF tests were enrolled consecutively. All patients underwent a black-on-white Amsler grid test for each eligible eye. They were asked to outline any perceived scotomas (areas with abnormal grid lines) on the grid and then describe verbally their perception of the scotomas. Examiners asked patients to clarify their descriptions. All descriptions used by patients were recorded in their own words, which were then sorted into descriptor categories according to similar themes. The number of descriptor categories was counted for each eye. 10–2 VF mean deviation (MD) was compared among eyes that reported different number of descriptor categories. The mean 10–2 VF MD values were compared among different descriptor categories. Results Fifty glaucoma patients (88 eyes) were included. Patients used a total of 44 different descriptors for their scotomas. Patients’ descriptors were classified into categories that incorporated similar themes, resulting in 4 overarching descriptor categories: Missing/White, Blurry/Gray, Black, and Not Aware. Fifty-two eyes reported one descriptor category and 19 eyes reported two descriptor categories (mean number of descriptor categories = 1.27±0.45). Eyes that reported two descriptor categories had worse VF MD than those that reported one (-17.86±10.31 dB vs. -12.08±7.53 dB; p = 0.012). When eyes were organized according to its combination of descriptor categories, each eye naturally sorted into one of the following 5 groups, in frequency order: Missing/White (27 eyes; 31%), Blurry/Gray (21 eyes; 24%), combined Missing/White and Blurry/Gray (19 eyes; 21%), Not Aware (17 eyes; 19%), and Black (4 eyes; 5%). The mean 10–2 VF MD severity order was Black (-21.18±10.59 dB), combined Missing/White and Blurry/Gray (-17.86±10.31 dB), Missing/White (-11.92±6.76 dB), Blurry/Gray (-10.55±7.03 dB), and Not Aware (-3.91±4.05 dB) (p<0.001). Conclusion Paracentral vision loss in glaucoma is perceived by patients. As the perception of scotomas and the variety of terms to describe scotomas are related to glaucoma severity, clinicians should pay attention to patients’ subjective descriptions of their glaucomatous VF loss. The historical notion that glaucoma patients lose their peripheral vision first and eventually look through a black tunnel needs to be updated to reflect the true perception of glaucoma.