An Examination of the Frequency of Paravascular Defects and Epiretinal Membranes in Eyes With Early Glaucoma Using En-face Slab OCT Images.

PURPOSE: To examine the frequency of paravascular defects (PDs) and macular epiretinal membranes (ERMs) in eyes categorized as having mild glaucoma or glaucoma suspect using en-face slab analysis of optical coherence tomography (OCT) scans. MATERIALS AND METHODS: Fifty-seven glaucomatous eyes, 44 low-risk suspect eyes, and 101 healthy control eyes were included in the study. The 101 glaucomatous and suspect eyes had a mean deviation better than -6 dB on the 24-2 visual field, and a spherical refractive error between±6 D or axial length <26.5 mm. Two OCT-graders masked to eye classification identified ERMs and PDs on en-face slab images of the macula and peripapillary retina using horizontal B-scans and derived vertical B-scans. RESULTS: Glaucomatous eyes had a significantly higher number of PDs and ERMs than healthy controls (PD, P<0.001; ERM, P=0.046) and low-risk glaucoma suspects (PD, P=0.004; ERM, P=0.043). PDs and/or ERMs were present in 16 of 57 (28.1%) glaucomatous eyes, 2 of 44 (4.5%) suspect eyes, and 3 of 101 (3.0%) control eyes. Further, PDs were present in 11 of the 57 (19.3%) glaucomatous eyes, 1 of the 44 (2.3%) suspect eyes and 0 of the 101 (0%) control eyes, ERMs were seen in 7 of the 57 (12.3%) glaucomatous eyes, 1 of the 44 (2.3%) suspects, and 3 of the 101 (3.0%) control eyes. CONCLUSIONS: Eyes with early glaucoma have a higher frequency of PDs and ERMs than suspects or controls and exhibit PDs even in the absence of ERMs or high myopia.

Optical Coherence Tomography and Glaucoma Progression: A Comparison of a Region of Interest Approach to Average Retinal Nerve Fiber Layer Thickness.

PURPOSE: To determine whether the change in the retinal nerve fiber layer (RNFL) thickness in a region of interest (ROI) is a better measure of glaucoma progression than the change in average circumpapillary (cp) RNFL thickness. METHODS: Disc cube scans were obtained with frequency domain optical coherence tomography from 60 eyes of 60 patients (age, 61.7±12.7 y) with early or suspected glaucoma and controlled intraocular pressure. The average time between 2 test dates was 3.2±1.8 years. En-face images of the scans from the 2 tests were aligned based on the blood vessels, and cp images were derived for an annulus 100 µm wide and 3.4 mm in diameter, centered on the disc. An ROI was defined as the portion of the circumpapillary retinal nerve fiber layer (cpRNFL) plot within the temporal disc that extended below the 1% confidence interval for ≥5 degrees. Trend analysis using multilevel mixed-effects models was used to compare the rates of change between ROI width and average cpRNFL thickness. RESULTS: In total, 26 of the 60 eyes had a total of 33 ROIs. The ROI width significantly increased between the 2 test dates (median, 4.9 degrees; Q1=1.03 degrees, Q3=10.5 degrees). In comparison, the average cpRNFL thickness did not decrease significantly over the same period (median, -0.7 µm; Q1=-2.7 µm, Q3=2.7 µm). Mixed-effects linear models confirmed significant ROI progression (P=0.015), but not average cpRNFL (P=0.878). CONCLUSIONS: In this population, RNFL thinning in a ROI is a better measure of progression than is average cpRNFL thickness change.

Defects Along Blood Vessels in Glaucoma Suspects and Patients.

PURPOSE: To examine the relationship between small hypodense regions ("holes") in the retinal nerve fiber layer (RNFL) seen on circumpapillary optical coherence tomography (OCT) images of glaucoma patients and suspects and the paravascular inner retinal defects (PIRDs) seen with OCT line scans near blood vessels in individuals without optic nerve disease but with high myopia and/or epiretinal membranes (ERMs). METHODS: Based upon the availability of wide-field, swept-source OCT scans, 19 eyes from 15 glaucoma patients or suspects were selected from a larger group of eyes with holes on circumpapillary frequency-domain OCT scans. Paravascular defects (PDs) were identified using en face slab images generated (ATL 3D-Suite) from 52-µm slabs just below the vitreal border of the inner limiting membrane by averaging reflective intensity. Paravascular defects were confirmed with B-scans from these images. RESULTS: For 13 of the 19 eyes, the appearance of the PDs fit the previously described PIRDs and extended well beyond the circumpapillary region. In the other 6 eyes, the PDs were restricted to a small region and did not fit the previously described appearance of PIRDs. In these eyes, the holes were associated with an arcuate defect of the RNFL. Of the 13 with PIRDs, 9 had ERMs and/or high myopia previously associated with PIRDs in otherwise healthy eyes. CONCLUSIONS: Holes seen on circumpapillary OCT scans of glaucoma patients and suspects are associated with local glaucomatous damage, as well as with PIRDs associated with high myopia and ERMs.

A Region-of-Interest Approach for Detecting Progression of Glaucomatous Damage With Optical Coherence Tomography.

IMPORTANCE: Detecting progression of glaucomatous damage is often challenging. OBJECTIVE: To test the feasibility of using frequency-domain optical coherence tomography (FD-OCT) and a region-of-interest (ROI) approach to measure progressive changes in glaucomatous damage. DESIGN, SETTING, AND PARTICIPANTS: Among a group of patients in an institutional glaucoma practice who were likely to show glaucoma progression, eyes with a history of an optic disc hemorrhage (DH) confirmed by stereophotography were followed up with FD-OCT cube scans of the optic disc. All patients underwent FD-OCT scans on at least 2 occasions separated by at least 1 year (mean, 3.45 years; range, 1.42-6.39 years). Because we were not studying the effects of an optic DH, no constraint was placed on the time between the documentation of an optic DH and the first scan used in the analysis. MAIN OUTCOMES AND MEASURES: After en face images of the FD-OCT scan were aligned based on the blood vessels, circumpapillary images were derived for an annulus 100 µm in width, and the retinal nerve fiber layer (RNFL) thickness profiles were plotted for the first and last visits. The ROI width associated with the optic DH was defined as the region of the RNFL profile below the 1% CI based on healthy norms. The change in the ROI width was compared with the change in the global RNFL thickness, which was obtained by averaging the circumpapillary RNFL thickness. RESULTS: The change in the ROI width (mean [SD], 8.0° [6.4°]; 95% CI, 4.9° to 11.1°; range, -0.7° to 19.3°) was significant (P < .001, 2-tailed t test) while the change in the global thickness (mean [SD], 2.40 [5.87] µm; 95% CI, -0.48 to 5.28 µm) was not significant (P > .12, 2-tailed t test). Although 15 of the 16 ROIs increased in width between visits, only 11 showed a decrease in the global RNFL thickness. CONCLUSIONS AND RELEVANCE: For detecting progression of local RNFL damage in patients with glaucoma, an OCT ROI approach appears superior to the OCT global RNFL thickness measure typically used.

Development of clinical visual physiology in China during the past fifty years.

In the past 50 years, China has experienced a valuable development stage of clinical visual physiology and made substantial progresses in the aspects. It not only contributes to ophthalmology development, but also cultivates the precious visual physiology scientist and researcher groups in China and will advance Chinese ophthalmology toward a glorious future.

Hypodense regions (holes) in the retinal nerve fiber layer in frequency-domain OCT scans of glaucoma patients and suspects.

PURPOSE: To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. METHODS: Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 ± 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 ± 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. RESULTS: Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. CONCLUSIONS: The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields.

A comparison of functional and structural measures for identifying progression of glaucoma.

PURPOSE: To compare glaucoma progression by functional and structural tests. METHODS: The authors prospectively studied 33 glaucoma patients (55 eyes); 20 eyes (15 patients) had disc hemorrhage, and 35 eyes (18 patients) had exfoliation glaucoma. The following tests were performed at two baseline and three follow-up examinations: frequency doubling perimetry (FDT), 24-2 Humphrey visual fields (HVF), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT). To identify progression, the baseline measurements were averaged and compared to those obtained at the final examination. Stereophotographs of the optic disc were obtained at baseline and compared with those at the final examination. RESULTS: Patients were followed up for 21.1±1.8 months. For HVF there were significant changes in mean deviation (MD) in eight (14.5%) eyes but in pattern standard deviation (P/SD) in only two (3.6%) eyes. For FDT, there were significant changes in MD in 13 (23.6%) eyes. Five eyes showed changes in MD for HVF and FDT. For mfVEP, there was an increase in abnormal points in nine (16.4%) eyes. Six of these eyes did not show significant HVF or FDT changes. For OCT, RNFL average thickness values were significantly decreased in nine (16.4%) eyes. Nine (16.4%) eyes showed progression on stereophotography; four of these eyes did not show significant changes on OCT and functional tests. CONCLUSIONS: Each test showed evidence of progression in some eyes. However, agreement among tests and stereophotography regarding which eyes showed progression was poor, illustrating the importance of following up patients with a combination of functional and structural tests.

A comparison of retinal nerve fiber layer (RNFL) thickness obtained with frequency and time domain optical coherence tomography (OCT).

To diagnose glaucoma and other diseases of the retinal ganglion cell/ optic nerve, the thickness of the retinal nerve fiber layer (RNFL) is routinely measured with optical coherence tomography. Until recently, these OCT measurements were made almost exclusively with a time domain OCT (tdOCT) machine from a single manufacturer. Recently, a number of OCT machines, based upon an improved frequency domain OCT technology (fdOCT), have appeared. We compared measurements made using a new fdOCT machine to those from the older tdOCT machine. The results were comparable. More importantly, we learned that the key factor determining whether results from different machines will be comparable is the algorithm used to segment RNFL thickness, not the type of OCT.

Feedback inhibition in the inner plexiform layer underlies the surround-mediated responses of AII amacrine cells in the mammalian retina.

Intracellular recordings were made from narrow-field, bistratified AII amacrine cells in the isolated, superfused retina-eyecup of the rabbit. Pharmacological agents were applied to neurons to dissect the synaptic pathways subserving AII cells so as to determine the circuitry generating their off-surround responses. Application of the GABA antagonists, picrotoxin, bicuculline and 1,2,5,6-tetrahydropyridine-4-yl methylphosphinic acid (TPMPA) all increased the on-centre responses of AII amacrine cells, but attenuated the off-surround activity. At equal concentrations, picrotoxin was approximately twice as effective as bicuculline or TPMPA in modifying the response activity of AII amacrine cells. These results indicate that the mechanism underlying surround inhibition of AII amacrine cells includes activation of both GABA(A) and GABA(C) receptors in an approximately equal ratio. Application of the GABA antagonists also increased the size of on-centre receptive fields of AII amacrine cells. Again, picrotoxin was most effective, producing, on average, a 54 % increase in the size of the receptive field, whereas bicuculline and TPMPA produced comparable 34 and 33 % increases, respectfully. Application of the voltage-gated sodium channel blocker TTX produced effects on AII amacrine cells qualitatively similar to those of the GABA blockers. Intracellular application of the chloride channel blocker 4,4'-dinitro-stilbene-2,2'-disulphonic acid (DNDS) abolished the direct effects of GABA on AII amacrine cells. Moreover, DNDS increased the amplitude of both the on-centre and off-surround responses. The failure of DNDS to block the off-surround activity indicates that it is not mediated by direct GABAergic inhibition. Taken together, our results suggest that surround receptive fields of AII amacrine cells are generated indirectly by the GABAergic, reciprocal feedback synapses from S1/S2 amacrine cells to the axon terminals of rod bipolar cells.