Péter Kóthy

Evaluation of continuous 24-hour intraocular pressure monitoring for assessment of prostaglandin-induced pressure reduction in Glaucoma

Purpose:To evaluate 24-hour continuous intraocular pressure (IOP) monitoring with a telemetric contact lens sensor (CLS) to detect prostaglandin-induced IOP reduction. Methods:In this prospective interventional study 9 ocular hypertensive and primary open-angle glaucoma patients were washed out from IOP-lowering medication for 6 weeks. One study eye per patient underwent 3 baseline 24-hour measurement curves 4 days apart: 2 curves with Sensimed Triggerfish CLS and 1 curve with Goldmann applanation tonometry (GAT). Then the patients received travoprost monotherapy for 3 months. The 24-hour CLS and GAT curves were repeated on the study eyes under treatment at the end of the third month. Results:The 24-hour GAT IOP (mean±SD) decreased from 22.91±5.11 to 18.24±2.49 mm Hg (P<0.001). In contrast, the means of the 3 CLS curves showed no significant difference (152.94, 142.35, and 132.98 au, P=0.273). No difference was seen when the SD values of the 3 CLS curves were compared (133.51, 132.18, and 110.98 au, P=0.497). All CLS curves showed an increasing time trend (P⩽0.001). Correlation of all 3 CLS curves of the individual eyes was high (r=0.726), but no correlation was seen between the corresponding CLS curve periods and GAT IOP values either at baseline (r=−0.223, P=0.546) or under treatment (r=0.320, P=0.402). No difference was seen between the erect/sitting (waking) and supine (sleeping) period CLS values (P>0.05). Conclusions:Our results suggest that the current CLS technique cannot be clinically used to monitor IOP decrease induced by topical medication in glaucoma, and has limited value in identification of transient IOP elevation periods.

Influence of LASIK on scanning laser polarimetric measurement of the retinal nerve fibre layer with fixed angle and customised corneal polarisation compensation

Background/aim: Retinal nerve fibre layer thickness (RNFLT), as measured with scanning laser polarimetry using the fixed angle corneal polarisation compensator (SLP-F), has been found to be reduced after uncomplicated laser assisted in situ keratomileusis (LASIK) compared to the pre-LASIK measurement. Since this virtual RNFLT thinning is attributed to the corneal changes induced by the LASIK, the authors investigated whether customised corneal polarisation compensation (SLP-C), which compensates for the actual corneal polarisation during each measurement, can avoid the LASIK induced, virtual changes of the polarimetric RNFLT values. Methods: Scanning laser polarimetry using both the SLP-F and SLP-C methods (GDx-Access, software version 5.0) was performed on 15 consecutive healthy subjects with no eye disease who underwent LASIK for ametropia correction. The SLP measurements were performed before the surgery, then on day 1 and day 6 after LASIK. Thickness data from images of one randomly selected eye per subject were analysed using the ANOVA and Scheffe multiple comparison tests. Results: Superior maximum, inferior maximum, normalised superior area, and normalised inferior area (SLP parameters representing the RNFLT at the superior and inferior poles of the optic nerve head) remained unchanged with SLP-C (ANOVA, p>0.05) but decreased (superior maximum, normalised superior area, Scheffe test, p<0.05) or tended to decrease (inferior maximum) after LASIK, when measured using SLP-F. In contrast, certain other parameters—namely, superior ratio and inferior ratio (representing the ratios between the superior or the inferior sector and the temporal sector), maximal modulation, and ellipse modulation decreased with SLP-C (Scheffe test, p<0.05), but remained stable with SLP-F (ANOVA, p>0.05) after LASIK. Superior to nasal ratio, symmetry of the superior and inferior RNFLT as well as the parameter showing the probability of having glaucoma (called “the number”) remained unchanged with both types of corneal compensation (ANOVA, p>0.05). With SLP-C the parameter ellipse average thickness increased after LASIK (Scheffe test, p = 0.021). No parameter value altered between day 1 and day 6 after LASIK, for either method. Conclusion: The results suggest that the LASIK induced decrease of the polarimetric RNFLT, which is consistently detected with polarimeters when using the fixed angle corneal polarisation compensator, is due to alterations of the corneal polarisation. The use of customised corneal polarisation compensation avoids this virtual decrease of the polarimetric RNFLTHowever, our results suggestan increase of the measured retardation in the temporal quadrant of the SLP-C image after LASIK. Since ratios of parameters using the temporal RNFLT in the denominator are important in the polarimetric glaucoma diagnosis algorithm, their decrease as a consequence of using SLP-C needs further investigation.

Personality traits, depression, and objectively measured adherence to once-daily prostaglandin analog medication in glaucoma

PurposeTo investigate the influence of personality traits, depression, and training on objectively measured adherence to once-daily prostaglandin analog medication. MethodsAdherence was measured with the Travalert Dosing Aid on 58 consecutive, regularly followed-up glaucoma patients already on self-administered travoprost. Before the 3-month data-collection period all patients received training on use of the device. Psychologic characteristics were measured using the State-Trait Anxiety Inventory, Eysenck Personality Questionnaire, and Beck Hopeless Scale and Depression Inventory. An adherent day was defined as travoprost instillation at 9 PM ±2 hours. ResultsAdherence was 77% for the total period. Social desirability was higher than normal (U test, P<0.0001). Seven patients (12.1%) showed mild-to-moderate depression, which was not significantly associated with decreased adherence (Kruskal-Wallis test, P=0.071). Severity of glaucoma, number of ocular and systemic medications, satisfaction with the recording device, and socio-economic characteristics had no influence on adherence. ConclusionsObjectively measured adherence to once-daily prostaglandin analog medication was good, and not influenced by treatment characteristics or patient factors including mild-to-moderate depression. The elevated social desirability suggests that self-reported adherence is not a reliable measure of adherence in glaucoma.

Accuracy of combined GDx-VCC and matrix FDT in a glaucoma screening trial

PurposeTo assess the advantage in glaucoma screening of the use of scanning laser polarimetry with customized cornea compensation (GDx-VCC) combined with Matrix Frequency Doubling Technology (M-FDT) testing. MethodsIn a nonpopulation-based prepublicized trial, self-recruited white participants were screened for glaucoma with GDx-VCC, with M-FDT, and by independent clinical examination. Cases with possible glaucoma as found with any of the screening methods underwent a detailed clinical investigation to verify or exclude glaucoma. Sensitivity, specificity, accuracy, likelihood ratios, and predictive values were calculated using different threshold criteria for GDx-VCC alone, M-FDT alone, and for various combinations. ResultsOf the 233 attendees, 181 participants (345 eyes) successfully underwent the GDx-VCC and M-FDT measurements. Thirty-nine eyes of 24 participants had glaucoma (11.3% prevalence among eyes tested successfully). All but 2 of the glaucomatous eyes had only early damage. Evaluated separately, the criterion GDx-VCC NFI (normal threshold ≤30) performed best, with 97.0% specificity, 88.8% accuracy, and 25.6% sensitivity; but with only 8.5 positive likelihood ratio (PLR). For paired criteria, the best combination of GDx-VCC-screening test with M-FDT-screening test provided 99.6% specificity, 91.3% accuracy, and 28.6 PLR. For NFI combined with GDx-VCC nerve fiber bundle defect criterion, specificity was 99.0%, accuracy 89.6%, and PLR 18.0. However, the sensitivities in the 2 cases fell to 12.0% and 18.0%. For a triple combination of M-FDT-screening test with the latter pair of criteria, sensitivity increased to 41.7% and PLR (13.6) still remained clinically useful. ConclusionsIn a self-recruited white population with relatively high risk for mild glaucomatous damage, a combination of GDx-VCC together with M-FDT could usefully be employed for mass glaucoma screening.

Influence of selective laser trabeculoplasty on 24-hour diurnal intraocular pressure fluctuation in primary open-angle glaucoma: a pilot study.

BACKGROUND AND OBJECTIVE To investigate the influence of selective laser trabeculoplasty on mean diurnal intraocular pressure (IOP) and diurnal IOP fluctuation in primary open-angle glaucoma. PATIENTS AND METHODS After washout from intraocular pressure-lowering drugs, a baseline diurnal IOP curve was obtained for 26 eyes of 13 patients before selective laser trabeculoplasty. The IOP curve was repeated at 3 and 6 months. RESULTS In five eyes, office time (8:00 a.m. to 12:00 p.m.) IOP decreased by 20% or more. No similar decrease was seen in mean diurnal IOP in any case. IOP-lowering drugs were required for 11 eyes before the 3-month visit. Baseline diurnal IOP was higher for these eyes than for the others (P = .002). Compared with baseline values, a significant decrease was seen in mean IOP at the 6-month visit (P = .017) and in IOP fluctuation at both visits (P < .001 and P = .004, respectively) for the eyes without drug treatment. CONCLUSION Although no eyes showed mean diurnal IOP reduction of 20% or more, selective laser trabeculoplasty resulted in a significant decrease in the amplitude of diurnal IOP fluctuation.

Accuracy of scanning laser polarimetry, scanning laser tomography, and their combination in a glaucoma screening trial.

PurposeTo compare the usefulness in glaucoma screening of scanning laser polarimetry (GDx-VCC), scanning laser tomography [Heidelberg retina tomograph II (HRT II)], and their combined evaluation. MethodsIn a nonpopulation-based prepublicized trial, self-recruited white participants were screened for glaucoma with GDx-VCC, HRT II, and by independent clinical examination. Cases with possible glaucoma as found with any of the screening methods underwent a detailed clinical investigation to verify or exclude glaucoma. ResultsOf the 136 attendees 118 participants (218 eyes) successfully underwent the GDx-VCC and HRT II measurements. Twenty-three eyes (11%) of 13 participants had glaucoma. Seventeen of these glaucomatous eyes (74%) had early damage. Evaluated separately, the GDx-VCC screening test (borderline cases grouped with the normal cases) performed best with 96.8% specificity, 89.5% accuracy, 7.5 positive likelihood ratio (PLR), but with only 23.8% sensitivity. Accuracy and PLR for all HRT parameters were <86.4% and <3.7, respectively. Combining different threshold criteria, for GDx-VCC accuracy increased to 90.3% to 90.8% and PLR to 14.0 to 17.7; but for HRT no useful increase was seen (accuracy <86.4% and PLR<4.7 for all combinations). Combination of the best HRT and GDx-VCC criteria resulted in a PLR which was increased compared with the HRT combinations, but decreased compared with the GDx-VCC combinations (PLR<12.7 for all combinations). ConclusionsIn this white screening population with relatively high risk for mild glaucomatous damage, a combination of different GDx-VCC criteria was useful for glaucoma screening; but combinations of HRT criteria or combinations of GDx-VCC criteria with HRT criteria were less good for this purpose.

Intraocular pressure reduction with travoprost/timolol fixed combination, with and without adjunctive brinzolamide, in glaucoma

ABSTRACT Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension. Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004 % , then switched to evening travoprost 0.004 % /timolol 0.5 % fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1 % ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period. Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p < 0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences. Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.

Endothelin-A Receptor Antagonist BQ-485 Protects against Intraocular Pressure Spike Induced by Laser Trabeculoplasty in the Rabbit

Purpose: We have previously shown in rabbits that the intraocular pressure (IOP) spike caused by argon laser trabeculoplasty (ALT) is associated with an acute endothelin-1 (ET-1) release from the uveal tissue into the aqueous humour. In this study we investigated whether pretreatment with an ETA receptor antagonist (BQ-485) protects against the pressure spike induced by ALT, in the rabbit model. Methods: Under general anaesthesia, 10 µl of 10–5M BQ-485 was injected into the anterior chamber of the right eye, and 10 µl of balanced salt solution (BSS) into the contralateral anterior chamber, for 12 pigmented rabbits. Five minutes later ALT (1,000 mW, 0.1 s, 100 spots over 360° focused on the iris pillars) was performed on both eyes of each animal. IOP was measured before the injections (baseline value), and also 30 min afterwards using a Tono-Pen XL tonometer. Immediately after the second IOP measurement aqueous humour was aspirated for measurement of ET-1 concentration. Results: The baseline IOP (mean ± SD) was 8.08 ± 1.73 mm Hg and 7.92 ± 1.78 mm Hg for the right and left eyes, respectively (Duncan test, p > 0.05). At 25 min after ALT the IOP of the BQ-485-pretreated right eyes remained unchanged (7.83 ± 2.44 mm Hg, p > 0.05) but the IOP of the BSS-pretreated left eyes at 30 min increased significantly to 10.67 ± 4.70 mm Hg (p < 0.05 for comparisons both with the corresponding baseline value for the same eye, and with the IOP of the contralateral eye at 30 min). There was no difference in aqueous humour ET-1 concentration between the corresponding right and left eyes (paired t test, p > 0.05). Conclusion: Intracameral BQ-485 pretreatment protected against the ALT-induced acute IOP elevation, but did not influence the laser-induced ET-1 release. This suggests that ETA receptor antagonists may potentially have a therapeutic role in the prevention of laser-induced IOP spikes.

LOXL1 gene sequence variants and vascular disease in exfoliation syndrome and exfoliative glaucoma.

PurposeTo investigate whether the single nucleotide polymorphisms (SNPs) of the LOXL1 gene associated with exfoliation syndrome (XFS) and exfoliative glaucoma (XFG) are different in XFS/XFG patients with and without cardiovascular disease (CVD); and to compare the allele frequencies in XFS/XFG with those in ischemic cerebrovascular disease (stroke), in the Hungarian population. MethodsG153D and R141L allele frequencies were determined for 56 XFS/XFG patients (10 patients with and 45 without CVD, 1 patient unclassified), and for 189 patients with stroke. ResultsFor G153D the frequencies of guanine (G) and adenine (A) alleles were 71.4% and 28.6% in the ischemic stroke group, and 58.0% and 42.0% in XFS/XFG (&khgr;2 test, P=0.008). The corresponding figures in XFS/XFG without CVD were 56.7% and 43.3%, and 60.0% and 40.0% in XFS/XFG with CVD (P=0.785). For R141L the frequencies of G and timidine (T) alleles were 68.2% and 31.7% in stroke patients, and 82.1% and 17.9% in XFS/XFG (P=0.004). No difference was seen for allele frequency distribution between XFS/XFG patients without and with CVD (84.4% and 15.6%; 80.0% and 20.0%, respectively, P=0.738). ConclusionsIn Hungarians, the frequency of G (risk) allele of G153D SNP was low in XFS/XFG. The frequency of G allele in R141L and G153D SNPs of the LOXL1 gene did not differ between XFS/XFG patients with and without CVD, but its frequency was different in XFS/XFG and ischemic stroke. These results suggest that the G allele in these SNPs has no direct role in the development of vascular diseases associated with XFS/XFG.

Risk factors associated with progression in exfoliative glaucoma patients

Purpose: To evaluate exfoliative glaucoma (XFG) patients over 5 years, determining risk factors associated with progression or non-progression of glaucoma. Methods: A retrospective, observational study. Patients were chosen from consecutive charts and data collected from each available visit included in the follow-up period. Data were abstracted for non-progressed XFG patients for 5 years and for progressed patients until glaucoma worsened. Progression was determined from patient records and by disc photographs. Results: There were 71 (53%) progressed and 63 (47%) non-progressed XFG patients.Baseline parameters demonstrated worse visual field damage (p = 0.014) and more prescribed medicines (p = 0.03) in progressed patients. The mean intraocular pressure (IOP) for progressed patients was 18.7 ± 4.3 and 17.3 ± 3.4 mm Hg for non-progressed patients (p = 0.047). The mean IOP that best separated the groups was 17 mm Hg with 60% staying non-progressed at or below this level and 30% above this level. At the last visit, progressed patients had more medicines prescribed (1.7) than non-progressed patients (1.3, p = 0.005). A multivariate regression analysis showed higher mean, peak and variance of IOP, number of glaucoma medications at the final visit and presence of a disc hemorrhage (n = 5) as independent risk factors for progression (p ≤ 0.05). Conclusion: IOP reduction in XFG may be essential in reducing disease progression. The presence of disc hemorrhage in XFG may suggest an increased probability of progression despite treatment to within the normal IOP range.