Lamina Cribrosa and Choroid Features and Their Relationship to Stage of Pseudoexfoliation Glaucoma.

Purpose: To better understand the relationship of lamina cribrosa (LC) and choroid features to the severity of pseudoexfoliation glaucoma (PXG). Methods: In this cross-sectional study, 137 eyes of 122 subjects (47 eyes with moderate/advanced PXG [mean deviation (MD), -15.0 ± 7.7 dB], 34 eyes with mild PXG [MD, -2.7 ± 1.5 dB], 32 aged-matched pseudoexfoliation syndrome [PXS] eyes, and 24 aged-matched control eyes) were investigated. Optic discs, LC thickness, and anterior LC depth (ALD; midsuperior, center, and midinferior) as well as peripapillary choroidal thickness were determined. Linear mixed modeling was used to adjust for age, sex, and axial length. Results: A progressive decrease in LC thickness was found when comparing controls (271.9 ± 61.3 µm), PXS (212.6 ± 51.5 µm), mild PXG (180.8 ± 24.6 µm), and moderate/advance PXG (138.9 ± 37.5 µm) (P < 0.001). ALD was greater (P < 0.001) in moderate/advance glaucoma (306.7 ± 105.3 µm) and mild PXG (209.5 ± 79.7 µm) compared with PXS (155 ± 86.7 µm) and healthy controls (149.2 ± 103 µm). Although eyes with moderate/advance PXG had the thinnest choroid (117.2 ± 36.6 µm), choroidal thickness was comparable in mild PXG, PXS, and controls (150.0 ± 46.1, 159.7 ± 65.5, and 157.5 ± 51.1 µm, respectively; P = 0.002). Worse MD was the only factor associated with thinner LC (ß = 2.344, P < 0.001) and choroid (ß = 1.717, P = 0.009 µm) in PXG eyes. Higher IOP (ß = 4.305, P = 0.013) and worse MD (ß = -6.390, P < 0.001) were associated with deeper ALD in PXG. Conclusions: In pseudoexfoliation, LC thinning is an early sign, and there is progressive thinning with advancing glaucoma. Choroidal thinning is observable only with moderate/advanced glaucoma. In PXG eyes, LC thickness, depth, and peripapillary choroidal thickness are associated with glaucoma severity.

Factors associated with lifetime risk of open-angle glaucoma blindness.

PURPOSE: To investigate factors associated with bilateral glaucoma blindness, particularly factors available at the time of diagnosis. METHODS: Retrospective chart review of all patients with primary open-angle glaucoma (POAG) or pseudoexfoliative glaucoma (PEXG) followed at the Department of Ophthalmology or Low Vision Center of Skåne University Hospital, Malmö, Sweden, who died between January 2006 and June 2010. Disease stage at diagnosis was defined by a simplified version of Mills' glaucoma staging system using perimetric mean deviation (MD) to define six stages of severity. Blindness was defined according to WHO criteria. We used logistic regression analysis to examine the association between risk factors and glaucoma blindness. RESULTS: Four hundred and 23 patients were included; 60% POAG and 40% PEXG. Sixty-four patients (15%) became blind from glaucoma. Blind patients had significantly longer mean duration with diagnosed disease than patients who did not go blind (14.8 years ± 5.8 versus 10.6 years ± 6.5, p < 0.001). The risk of blindness increased with higher intraocular pressure (IOP) (OR 1.08, 95% CI 1.03-1.13) and with each stage of more advanced field loss at time of diagnosis (OR 1.80 95% CI 1.34-2.41). Older age at death was also associated with an increased risk of blindness (OR 1.09 95% CI 1.03-1.14), while age at diagnosis was unimportant. PEXG was not an independent risk factor for blindness. CONCLUSIONS: Higher IOP and worse visual field status at baseline were important risk factors, as was older age at death.

Performance of time-domain and spectral-domain Optical Coherence Tomography for glaucoma screening.

PURPOSE: To investigate the measures of validity for selective or population screening of the time-domain Stratus and the spectral-domain Cirrus Optical Coherence Tomography (OCT) imaging techniques in a population-based sample and in clinical glaucoma patients at different stages of glaucoma. PATIENTS AND METHODS: A random sample of 307 subjects living in two rural areas in southern Sweden, and a random sample of 394 clinical glaucoma patients were selected. A large battery of examinations, including Stratus and Cirrus OCT was performed. OCT retinal nerve fibre layer (RNFL) thickness analyses for average thickness, quadrant and clock-hour sectors were compared with normative significance limits available in the instruments. RESULTS: The population-based sample included 129 healthy and nine glaucoma subjects, and the sample of clinical glaucoma patients included 138 patients. Specificity and positive predictive values were generally better with Stratus than for Cirrus, and sensitivity was generally better with Cirrus. With the average RNFL thickness parameter, Stratus reached 100% specificity and a positive predictive value of 100% and 68% sensitivity in the whole group of the clinical glaucoma patients, but sensitivity was only 28% among the earliest stage glaucoma patients. Sensitivity increased considerably when relying on the quadrant sector parameter, while specificity decreased only marginally. CONCLUSION: Stratus, with high specificity and positive predictive values, seemed to be best of choice for screening purposes, while Cirrus, with high sensitivity, was the better choice for early detection.

Characteristics of pseudoexfoliation in the Thessaloniki Eye Study.

PURPOSE: To report on the prevalence of pseudoexfoliation (PEX) and its association with ophthalmic characteristics and systemic diseases in a well-defined population. METHODS: The Thessaloniki Eye study is a cross-sectional population-based study of chronic eye diseases in Thessaloniki, Greece. Participants with PEX were identified by clinical examination and were compared with those without PEX with regards to ophthalmic characteristics and systemic diseases, after adjusting for age and sex. RESULTS: PEX was found in 11.9% of the 2261 clinic-visit participants. Participants with PEX, compared with those without, had higher intraocular pressure, larger vertical cup-to-disc ratio, and higher percentage with vertical cup-to-disc ratio asymmetry and optic disc damage. The proportion with glaucoma among pseudoexfoliative participants (15.2%) was higher than that for glaucoma among nonpseudoexfoliative participants (4.7%). After excluding glaucoma participants, the only difference was the 0.6 mm Hg higher intraocular pressure in participants with PEX. Compared with nonpseudoexfoliative eyes, the presence of PEX on iris only or on both iris and lens was associated with higher intraocular pressure, whereas the presence of PEX on lens only was not. PEX was not associated with any systemic disease. CONCLUSIONS: The prevalence of PEX in Greece is relatively high compared with other white populations. PEX was associated with higher intraocular pressure and higher percentage with optic disc damage, secondary to the higher proportion with glaucoma among pseudoexfoliative participants than among nonpseudoexfoliative participants. In nonglaucoma participants, eyes with PEX had only slightly higher intraocular pressure, but this was not observed in eyes with PEX on lens only.

Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma.

PURPOSE: To investigate the concentration of tumor necrosis factor (TNF)-alpha in the aqueous humor of patients with glaucoma, including correlations with glaucoma subtypes and intraocular pressure. METHODS: The study population comprised 84 patients with open-angle glaucoma who were scheduled for filtration or cataract surgery. Glaucoma subgroups included 29 cases of primary open-angle glaucoma (POAG), 28 cases of normal-tension glaucoma (NTG), and 27 cases of exfoliation glaucoma (ExG). Seventy-nine patients with senile cataract were recruited as control subjects. The concentrations of TNF-alpha in the aqueous humor were measured with an enzyme-linked immunosorbent assay. The percentages of samples positive for TNF-alpha and the measured concentrations in the glaucoma and cataract groups were compared. In addition, the relationships with the glaucoma subtypes, intraocular pressure, and glaucoma severity were analyzed. RESULTS: A significantly higher percentage of subjects in the glaucoma group were positive for TNF-alpha compared with the cataract group (P = 0.011). The mean TNF-alpha concentrations among the positive cases were not different between the groups (P = 0.689). TNF-alpha-positive samples were higher in the POAG (13.7%) and NTG (10.7%) subgroups than in the cataract group without significance, but higher in ExG subgroup (29.6%) with significance (P = 0.001). Relationships between the TNF-alpha concentration and the intraocular pressure or the clinical stage of glaucoma were not observed. CONCLUSIONS: TNF-alpha levels were significantly higher in the glaucoma group than in the cataract group, with a particularly large difference observed in those with ExG. The results suggest that TNF-alpha plays a key role in the progression of glaucoma.

Ultrasound biomicroscopy of zonular anatomy in clinically unilateral exfoliation syndrome.

PURPOSE: To evaluate the ability of ultrasound biomicroscopy (UBM) to detect abnormalities in the zonular apparatus in unaffected eyes of patients with clinically unilateral exfoliation syndrome (XFS) using a standardized grading system. METHODS: The affected and unaffected eyes of 17 patients with clinically unilateral XFS and 17 eyes of 17 control subjects underwent UBM. Radial sections detailing the lens and zonules at 12:00, 1:30, 3:00, 4:30, 6:00, 7:30, 9:00 and 10:30 clock hours were obtained. The images were graded by a masked, experienced UBM observer using a standardized scoring system based on the zonular appearance (0, none; 1 and 2, uneven or disrupted zonules with or without patchy deposits; 3, diffuse granulation, thick zonules or both; 4, total zonular disruption). Affected meridians were compared by the Friedman test, while distributions of unaffected and affected eyes were compared using the Student t-test. RESULTS: In the control group, 15/17 eyes showed normal zonules; the remaining two eyes showed grade 1 changes in some meridians. The mean grade score was 0.33 [standard deviation (SD) 0.84]. Eyes with XFS had a higher score than control eyes, with a mean score of 14.35 (SD 7.14, P < 0.001, Student t-test). In clinically unaffected fellow eyes, the mean score was 10.53 (SD 7.44), and was less than that of XFS eyes (P = 0.008, Student t-test). Twelve XFS eyes (71%) and six unaffected fellow eyes (35%) had grade 3 or 4 in at least one meridian (P = 0.07, Friedman test). CONCLUSION: Bilateral zonular involvement is present in subjects with clinically unilateral XFS. These zonular changes may be extensive in fellow eyes without clinically evident exfoliation material. UBM assessment of zonular status in fellow eyes prior to cataract extraction may aid in surgical planning.

Ultrasound biomicroscopic assessment of zonular appearance in exfoliation syndrome.

PURPOSE: To assess zonular appearance using biomicroscopy (UBM) in exfoliation syndrome (XFS). METHODS: Normal eyes and eyes with XFS were enrolled in this prospective, consecutive, comparative cohort study. Following pupillary dilation, XFS patients were classified into three clinical stages (early, moderate or severe) by a single examiner (R.R.). Cross-sectional zonular UBM images were obtained circumferentially at eight evenly spaced locations. Five experienced observers evaluated the images using a standardized scoring system based on the zonular appearance (0, none; 1, early; 2, moderate; 3, severe). The extent of zonular involvement on UBM based on UBM score of all observers was correlated with the clinical stage of XFS using a five-stage classification. RESULTS: We enrolled 44 eyes (44 patients), 11 normal and 33 with XFS (10 early, 10 moderate and 13 severe) [mean age 69.4 +/- 9.9 (SD) years; range 50-87 years]. UBM scores of all observers were significantly different between the normal/early and moderate/severe groups (P < 0.001, t-test). With discriminant analysis, the predicted XFS stage showed good agreement with the clinical staging [all kappa > 0.61, area under receiver operating characteristic (ROC) curve > 0.86]. CONCLUSION: UBM can detect zonular involvement in XFS and may be useful in preoperative planning. This may be important in eyes with posterior synechiae in which a diagnosis and the severity of XFS cannot be determined on slit-lamp examination.

[Correlation between confocal tomography of the optic nerve (HRT) and the perimetric frequency doubling technology]. / Korrelation zwischen der konfokalen Tomographie des Nervus opticus (HRT) und der perimetrischen Frequenzverdoppelungstechnik (FDT).

PURPOSE AND METHODS: To correlate the five phases of optic nerve (ON) damage staging, as assessed by means of confocal tomography (HRT) with the five stages of visual field, assessed by conventional perimetry (standard automatic perimetry, SAP) and classified in five stages according to the "GLAUCOMA STAGING SYSTEM". The second step was to correlate the same optic nerve staging system with the results of the visual field tested with non-conventional perimetry using the frequency doubling technology (FDT) employing the Humphrey-Zeiss and Welch-Allyn perimeter. The five stages of FDT visual field data evolution were classified according to the new "FDT STAGING SYSTEM". MATERIAL: 58 visual fields of 58 consecutive selected patients with either ocular hypertension or glaucoma with an age-range between 15 and 65 years. METHOD: Visual field examination was performed with conventional (Octopus G2 threshold test) and non-conventional perimetry (FDT N30 threshold test), and the ON was assessed with confocal tomography (Heidelberg Retina Tomograph). RESULTS: In 40 % of the visual fields tested normal with conventional perimetry, non-conventional perimetry (FDT) detected glaucomatous visual field defects corresponding topographically with the optic nerve damage revealed by HRT. CONCLUSIONS: New non-conventional perimetric techniques such as FDT enable the very early detection of visual field defects topographically correlated to optic nerve damage.