Application of optical coherence tomography in glaucoma suspect eyes

Purpose: The aim of the study was to compare the optical coherence tomography (OCT) parameters of the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) and to identify which measurements are best able to differentiate between normal and glaucoma suspect eyes. Methods: The study included 27 eyes with ocular hypertension (OHT), 33 eyes with pre‐perimetric glaucoma (PG), 30 perimetrically unaffected eyes of patients with glaucoma in the fellow eye (FE) and 58 eyes of age‐matched normal volunteers. All subjects underwent a complete eye examination with standard automated perimetry, optic disc photography and OCT imaging. Peripapillary ‘fast RNFL thickness scans’ and ‘fast optic disc scans’ were performed with time‐domain OCT. The ONH and RNFL parameters were compared among the four study groups. The ONH and RNFL parameters were examined alone and then combined via four linear discriminant functions (LDF): LDF 1, the optimal combination of ONH parameters; LDF 2, the optimal combination of RNFL parameters; LDF 3, the optimal combination of both ONH and RNFL parameters; and LDF 4, the optimal combination of the best 11 parameters. The areas under the receiver operating curves (AUC) and the sensitivity at fixed specificity of at least 80 and 95 per cent were calculated for single parameters and LDF combinations and then compared. The best 11 parameters were selected based on their AUC values. Results: Comparative analysis of OCT parameters revealed statistically significant differences in all seven ONH parameters in both PG and FE groups (and only in one ONH measurement in the ocular hypertensive group) when compared with normal eyes. Most of the RNFL parameters demonstrated statistically significant differences in all of the study groups when compared with the control group. The max‐min parameter (0.835), inferior quadrant (0.833) and average RNFL thickness (0.829) obtained the highest AUC values in the whole glaucoma suspect group. The rim area had the best diagnostic accuracy among the ONH parameters (AUC = 0.817). The AUC values of the four LDF were: 0.825 (LDF 1), 0.882 (LDF 2), 0.902 (LDF 3) and 0.888 (LDF 4). Statistically significant differences were found between the AUC values of the single best ONH and RNFL parameters and LDF 3 and LDF 4. Conclusions: In the present study, RNFL parameters presented with better discriminatory abilities than ONH parameters in the OHT and FE groups. The ONH parameters demonstrated better diagnostic precision in differentiating between PG and normal eyes. The average RNFL thickness, max–min parameter and inferior quadrant RNFL thickness had the best abilities among single OCT measurements for discriminating between glaucoma suspect (including all ocular hypertensive, PG and FE eyes) and normal eyes. The combination of RNFL parameters only or both ONH and RNFL parameters, using linear discriminant analysis, provided the best classification results, improving the diagnostic accuracy of the instrument.     

The parapapillary region of normal and glaucoma eyes. I. Planimetric values of 312 glaucoma and 125 normal eyes

Magnification-corrected planimetry of the parapapillary region was performed according to Littmann's method in 312 unselected eyes with chronic primary open-angle glaucoma and in 125 normal eyes of an age- and refraction-matched control group using optic disk photographs. The glaucoma group was divided into five pathomorphologic subgroups. High myopics (less than -8.00 D) and "ocular hypertensives" had been excluded. The coefficient of variation ranged intraindividually from 0.0 to 0.17 and interindividually from 0.0 to 0.16. Two different morphologic variants were defined and examined: 1) Zone "Alpha" with incipient to advanced parapapillary chorio-pigmentepithelio-retinal atrophy - characterized by irregular hypo- and hyperpigmentation - was statistically proven in the control group (0.60 +/- 0.44 mm2; p less than 0.05; Wilcoxon-Mann-Whitney test) to be smaller than in the glaucoma group (0.81 +/- 0.70 mm2). It increased significantly (p = 0.0000) with advancing glaucoma stage. In the glaucoma and normal group it was broadest in the temporal horizontal sector (p less than 0.001; Wilcoxon test), followed by the temporal lower (p less than 0.001), temporal upper (p less than 0.001) and nasal sectors (p less than 0.001). There was no significant difference in prevalence between the two groups. 2) Zone "Beta" with subtotal to total parapapillary chorio-pigment-epithelio-retinal atrophy was also smaller in the normal eyes (0.18 +/- 0.52 mm2, prevalence: 20.0%; p = 0.0000) than in the glaucomatous ones (0.85 +/- 1.42 mm2, prevalence 66.7%) and was also, in both groups, broadest in the temporal horizontal sector, followed by the temporal lower, temporal upper and nasal sectors. In the control group it was smaller than zone "Alpha" (p less than 0.00001), while in the glaucoma group there was no difference. 3) The difference between normal eyes and earliest glaucoma stage I was for zone "Beta" (p = 0.0000); the difference between the normal eyes and those of glaucoma stage II was significant for both zones (p = 0.0000 and p less than 0.05, respectively). In both groups and in all glaucoma stages both zones were larger in the lower half of the optic disk than in the upper half. 4) "Conus pigmentosus" and the peripapillary scleral rim in normal and glaucomatous eyes showed no significant difference as regards their area and frequency. The parapapillary chorio-pigmentepithelio-retinal alterations are precursors of, or are equivalent to the so-called "halo glaucomatosus".(ABSTRACT TRUNCATED AT 400 WORDS)     

Outflow changes in normal eyes after closed-angle glaucoma.

Twenty-four patients with spontaneous acute closed-angle glaucoma in one eye were selected for study. All 24 eyes had a peripheral iridectomy, were normotensive, and had no gonioscopically visible peripheral anterior synechiae. Of the 24 contralateral eyes 14 gave a positive response to provocative tests and had peripheral iridectomy. The remaining 10 eyes did not give positive responses to the tests and were on no treatment. The 24 pairs of eyes were provoked with pilocarpine and phenylephrine. Tonography was performed at the start of the test, 1 1/2 hours later, and at its termination. At the start of the test the 24 eyes that had had spontaneous closed-angle glaucoma showed a higher pressure and lower outflow facility than the 24 contralateral eyes. This difference disappeared as the test progressed. It is concluded that apparently normal eyes--after an acute attack--do none the less show a significant degree of damage to the outflow system. Ten pairs of eyes from 10 normal persons were provoked in a similar fashion and at no point did a significant difference appear between right and left eyes.     

Factors affecting ocular pulse amplitude in eyes with open angle glaucoma and glaucoma‐suspect eyes

Purpose: To investigate the associations between ocular pulse amplitude (OPA) as measured by dynamic contour tonometry (DCT) and ocular and systemic factors in patients with open angle glaucoma (OAG) and in glaucoma suspects. Methods: One hundred and seventy‐three glaucoma‐suspect patients were consecutively enrolled. All subjects underwent intraocular pressure (IOP) measurement by DCT and Goldmann applanation tonometry (GAT), OPA measurement by DCT, Humphrey visual field (HVF) examination and central corneal thickness measurements. Arterial pulse amplitude (APA) and ocular perfusion pressure (OPP) were defined as the difference between systolic and diastolic BP and the difference between mean arterial pressure and IOP, respectively. All subjects also completed a systemized questionnaire on systemic vascular morbidities. Results: Seventy‐four eyes were diagnosed with OAG, based on HVF results. The overall mean CCT was 538.2 ± 37.6 μm. In all 173 eyes, OPA was associated with spherical equivalent (SE, p < 0.001) and with IOP by GAT (p = 0.013) by multivariate analysis. Multivariate analysis of the 77 subgroup eyes of patients for whom BP parameters were available also revealed that OPA was associated with SE (p = 0.007) and with IOP by GAT (p < 0.001). When the subjects were classified into the groups with low, intermediate and high cardiovascular risk based on the questionnaire, there was no difference in OPA among these groups (p > 0.05). Conclusions: Ocular pulse amplitude was associated with IOP measured by GAT and SE in patients with OAG and in glaucoma suspects. There was neither significant correlation between systemic hemodynamic parameters and OPA, nor difference of OPA in patients with different cardiovascular risk. OPA is primarily a measure of pressure, and there are certain limitations towards its use as a hemodynamic index.     

The retinal nerve fiber layer in normal eyes and in glaucoma. I. Semiquantitative data of 398 eyes with glaucoma

Atrophy of the optic nerve is associated with changes of the retinal fiber layer (RNFL). Using red-free photographs the authors examined the RNFL of 398 eyes with chronic primary open-angle glaucoma and compared it with the RNFL of 234 normal eyes. The glaucoma group was divided into five stages and the fundus into four sectors. Differences between the normal and glaucoma eyes were: (1) The sequence of the sectors, with regard to the best visibility of the retinal nerve fiber bundles, was changed. In the normal eyes the nerve fiber bundles were most often best visible in the inferior temporal sector, followed by the superior temporal sector, the temporal horizontal area and finally the nasal region. In the glaucoma group the nerve fiber bundles were significantly more often best detectable in the superior temporal sector and the temporal horizontal area. (2) The degree of visibility of the retinal nerve fibers decreased significantly with increasing glaucoma stage. (3) Localized defects were seen in 15% of the eyes with glaucoma and none of the normal eyes. The specificity of this qualitative parameter was, therefore, 100%. The defects were found most often in the superior and inferior temporal regions. These differences between normal and glaucomatous eyes were also significant for the first glaucoma stage of this study. The localization of the foveola below the optic disk center (0.53 +/- 0.34 mm in the glaucoma group and 0.55 +/- 0.29 mm in the normal eyes) was not significantly different.     

Parapapillary chorioretinal atrophy in normal and glaucoma eyes. II. Correlations

The parapapillary chorio-pigment-epithelio-retinal atrophy in glaucomatous eyes is significantly larger than in normal eyes. In a previous study its area and frequency have been measured in 582 eyes of 321 patients with chronic primary open-angle glaucoma and in 390 eyes of 231 normal subjects. In the current study the parapapillary changes were correlated with intrapapillary morphometric data and with perimetric indices. The parapapillary chorioretinal atrophy was significantly correlated with the neuroretinal rim area, the horizontal and vertical cup/disc ratios, the quotient of horizontal to vertical cup/disc ratio, the retinal nerve fiber layer score, and the mean visual field loss. It was larger in the same sector where the neuroretinal rim loss was more marked. The correlation coefficients were generally higher for zone "Beta," characterized by complete chorioretinal atrophy with visible large choroidal vessels and sclera, than for zone "Alpha," which showed irregular hypo- and hyperpigmentation. The parapapillary chorioretinal atrophy was correlated in location and time with the intrapapillary glaucomatous changes. It deserves attention in glaucoma diagnosis and follow-up. Its evaluation is especially valuable in eyes with small optic nerveheads (disc size less than 1.6 mm2) in which the intrapapillary glaucomatous changes occur later than the parapapillary ones.     

Optic disc histomorphometry in normal eyes and eyes with secondary angle-closure glaucoma

Parapapillary atrophy has been reported to occur in glaucoma eyes. Seeking the microscopical equivalent, we evaluated histomorphometrically serial sections of 21 human eyes enucleated due to secondary angle-closure glaucoma and 28 nonglaucomatous eyes with malignant choroidal melanoma. In the parapapillary region two zones were differentiated: in zone B adjacent to the optic disc, Bruch's membrane was denuded of retinal pigment epithelium cells; zone A peripheral to zone B showed pigment irregularities in the retinal pigment epithelium. Both zones B and A were significantly larger and zone B occurred more frequently in glaucomatous eyes than in the control group. Additionally, the outer and inner retinal layers and the parapapillary retina as a whole were significantly thinner in the glaucoma eyes than in the control eyes. Photoreceptors were completely lost or markedly decreased in number in zone B The findings may indicate that zones B and A represent the histological correlate of the glaucomatous parapapillary chorioretinal atrophy. Offprint requests to: J. JonasSupported by Deutsche Forschungsgemeinschaft DFG Nan 55/61/Jo, and Förderverein Augenheilkunde Erlangen     

Optic disc histomorphometry in normal eyes and eyes with secondary angle-closure glaucoma

The intrapapillary region of the optic disc shows ophthalmoscopical changes in glaucoma. In search of a histological correlate, this region was examined histomorphometrically in serial sections of 21 human eyes with secondary angle-closure glaucoma and 28 control eyes with malignant choroidal melanoma. The lamina cribosa was significantly (P less than 0.05) thinner, the optic cup deeper and wider, the peripapillary scleral ring finer, and the corpora amylacea count was lower in glaucoma eyes than in control eyes with normal optic nerves. There was no significant difference in optic disc diameter. The decrease in lamina cribrosa thickness may be one of several factors leading to glaucomatous optic nerve fiber loss. Due to a decrease in the relative height the inner limiting membrane should not be taken as the reference level for optic-cup-depth measurement. A high corpora amylacea count may point to a normal optic nerve fiber population.     

Parapapillary retinal vessel diameter in normal and glaucoma eyes. II. Correlations

The juxtapapillary diameters of the superior temporal and inferior temporal retinal artery and vein have been shown to be significantly smaller in glaucomatous eyes than in normal eyes. They had been measured in 473 eyes of 281 patients with chronic primary open-angle glaucoma and in 275 eyes of 173 normal subjects. In the current study the vessel diameters were correlated with intra- and parapapillary morphometric data and visual field indices. Only one eye per patient and subject was taken for statistical analysis. The retinal vessel calibers were significantly (P less than 0.001) correlated with: (1) the area of the neuroretinal rim as a whole and in four different optic disc sectors; (2) the rim width determined every 30 degrees; (3) the optic cup area and diameters; (4) the horizontal and vertical cup/disc ratios and (5) the quotient of them; (6) the retinal nerve fiber layer score; (7) the area of the parapapillary chorioretinal atrophy; and (8) the visual field indices. In the same eye the vessel caliber was smaller in that sector where the neuroretinal rim loss was highest and the retinal fiber layer score lowest. In intraindividual comparison the vessels were smaller in that eye with less neuroretinal rim tissue and lower nerve fiber layer score. No significant correlations were found with the form of the optic disc, the area of the peripapillary scleral ring, side, sex and refraction. The correlation coefficients were not significantly different when the control group was matched for age. The parapapillary retinal vessel diameter decreases with advancing glaucomatous optic nerve damage. It is correlated with morphometric intra- and parapapillary glaucomatous changes and perimetric defects.     

Parapapillary chorioretinal atrophy in normal and glaucoma eyes. I. Morphometric data

Glaucomatous optic nerve damage is associated with alterations of the intra- and parapapillary optic disc area. We measured and compared the parapapillary region in 582 eyes of 321 patients suffering from chronic primary open-angle glaucoma and in 390 eyes of 231 normal subjects. Only one randomly assessed eye per patient and subject was taken for statistical analysis. Highly mopic eyes with a myopic refractive error of more than -8.00 diopters had been excluded. The parapapillary chorioretinal atrophy was divided into a peripheral zone "Alpha" with irregular hyper- and hypopigmentation, and a more central zone "Beta" characterized by whitish colour, visible large choroidal vessels and visible sclera. In the normal eyes both zones were significantly (P less than 0.001) largest and most common in the temporal horizontal sector, followed by the inferior temporal sector, the superior temporal sector and finally the nasal sector. In the glaucoma group both zones were significantly larger (P less than 0.0001; Mann-Whitney test) and more frequent than in the normal eyes (0.40 +/- 0.32 mm2 versus 0.65 +/- 0.49 mm2 for zone Alpha, 0.13 +/- 0.42 mm2 versus 0.79 +/- 1.17 mm2 for zone Beta). The differences were significant also for the earliest glaucoma stage of this study. They were most marked for the nasal parapapillary sector. Significant differences (P less than 0.001) between the normal group and the earliest glaucoma stage were: zone Alpha larger than 0.20 mm2 or broader than 0.20 mm in the temporal horizontal sector, total area of zone Alpha larger than 0.30 mm2, occurrence of zone Alpha in the nasal sector, and occurrence of zone Beta anywhere.     

Long-term changes in intraocular pressure after clear corneal phacoemulsification: normal patients versus glaucoma suspect and glaucoma patients.

PURPOSE: To compare the effects of clear corneal phacoemulsification on intraocular pressure (IOP) in patients without glaucoma, glaucoma suspects, and patients with glaucoma. SETTING: Urban, multisubspecialty private practice. METHODS: A retrospective analysis of patients who had clear corneal phacoemulsification with a minimum of 12 months follow-up was performed. The patients were divided into 3 groups: no glaucoma (NG), glaucoma suspects (GS), and glaucoma (GG). None had a history of prior surgery. Glaucoma suspects included patients with elevated IOPs, abnormal discs, pseudoexfoliation syndrome, or pigment dispersion syndrome on no medications and with no field defects. Glaucoma patients had received only medical treatment. Two-tailed, homoscedastic t tests were used for statistical analysis. RESULTS: There were 143 patients (164 eyes) in the NG group, 65 (75) in the GS group, and 61 (71) in the GG group. The mean preoperative IOP was 16.42 mm Hg +/- 2.77 (SD), 17.59 +/- 4.15 mm Hg, and 16.97 +/- 4.86 mm Hg in the 3 groups, respectively. At 1 year, the mean IOP was lower in all groups: 14.37 +/- 2.97 mm Hg, 15.68 +/- 3.38 mm Hg, and 15.86 +/- 4.00 mm Hg, respectively. The change was statistically significant in the NG and GS groups. Glaucoma patients showed a statistically significant reduction in the number of glaucoma medications postoperatively. CONCLUSION: Clear corneal phacoemulsification was associated with a statistically significant long-term reduction in IOP.     

Parapapillary retinal vessel caliber. II. Caliber reduction in eyes with glaucoma (a papillometric study of 309 eyes with chronic simple glaucoma compared with 264 normal eyes)

The diameter of the temporal superior or inferior artery and vein was measured at the optic disk border and 2 mm from the disk center in 309 nonselected eyes with chronic primary open-angle glaucoma. The values obtained were compared with those of 264 nonselected normal eyes. The calibers of both vessels were significantly larger in the normal eyes than in the glaucomatous ones (p = 0.000 or p less than 0.01; Wilcoxon-Mann-Whitney test). Their diameters diminished significantly (p less than 0.001) with decreasing width and area of the neuroretinal rim as a whole and when divided into different optic disk sectors, and with increasing optic cup area, horizontal and vertical cup/disk ratios, area of the subtotal to total parapapillary choriopigmentepithelioretinal atrophy, perimetric loss, and glaucoma stage. Thus, the caliber of the parapapillary retinal vessels decreases significantly with increasing glaucomatous optic nerve damage.     

Detection of progressive macular thickness loss using optical coherence tomography in glaucoma suspect and glaucomatous eyes

Aims

To examine the rate of macular thickness loss using time-domain optical coherence tomography (OCT) in functionally progressing versus non-progressing eyes, determined by standard automated perimetry (SAP).

Methods

Glaucoma suspects (GS) and glaucomatous (G) eyes underwent SAP and OCT imaging every 6 months. Functional progression was determined using pointwise linear regression, defined as 2 contiguous locations losing ≥1.0 dB/year at P<1.0% in the same hemifield. The annual rate of macular thickness loss was calculated from inner and outer regions of the macular map.

Results

72 eyes (43 GS and 29G) with ≥30 months of follow-up were enroled. Fourteen eyes demonstrated SAP progression. The annual rate of macular thickness loss (μm/year) in progressing eyes was faster (all P<0.05) than non-progressing eyes in temporal outer (−1.90±2.97 vs 0.33±2.77), nasal inner (−1.70±2.66 vs 0.14±2.76), superior inner (−2.15±4.57 vs 0.51±2.99), temporal inner quadrants (−2.58±5.05 vs −0.38±2.34), and the average of inner macular quadrants (−1.84±2.90 vs 0.03±2.10). The rate of loss in the nasal inner (P=0.02) and temporal outer (P=0.02) macular regions was associated with optic disc haemorrhage.

Conclusions

Eyes with SAP progression have significantly greater rates of macular thickness loss consistent with glaucomatous retinal ganglion cell atrophy, as compared with non-progressing eyes.