Andreas U Bayer

Association of glaucoma with neurodegenerative diseases with apoptotic cell death: Alzheimer’s disease and Parkinson’s disease

PURPOSE To report a possible association of glaucoma with Parkinsons disease and Alzheimers disease. METHODS Retrospective chart review (observational case series). The ophthalmologic charts of 49 patients with Alzheimers disease and of 38 patients with Parkinsons disease were reviewed to determine the occurrence rate of glaucoma among these patients. RESULTS Glaucomatous visual field defects or cup-to-disk ratios of 0.8 or greater were recorded in 12 patients with Alzheimers disease (24.5%) and in 9 patients with Parkinsons disease (23.7%). CONCLUSION Patients with Alzheimers disease and Parkinsons disease may have an increased occurrence rate of glaucoma.

Short wavelength automated perimetry, frequency doubling technology perimetry, and pattern electroretinography for prediction of progressive glaucomatous standard visual field defects

PURPOSE To evaluate the clinical use of a test battery of short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), and pattern electroretinography (PERG) in predicting progressive glaucomatous visual field defects on standard automated perimetry (SAP). STUDY DESIGN A prospective, longitudinal, observational case series. PARTICIPANTS One hundred and fifty-two patients with primary open-angle glaucoma (POAG) with bilateral glaucomatous visual field defects on SAP were followed at 6-month intervals over a period of 30 months. MAIN OUTCOME MEASURES Short wavelength automated perimetry, FDT, and PERG results were compared between POAG eyes with and without progressive field loss on SAP. These two groups were used to evaluate whether PERG, SWAP, and/or FDT is predictive of future progression of field loss on SAP. RESULTS Using the criteria of progressive field loss on SAP defined by the Collaborative Normal Tension Glaucoma Study, 54 eyes (study group) of 54 POAG patients showed progressive defects, whereas 84 eyes (control group) of 84 POAG patients showed no progression. Only 11.1% (6 of 54) of the eyes with a progression of field loss on SAP showed no increase of deficits on the three functional tests before progression. Short wavelength automated perimetry detected early progressive defects on SAP in 43 of the 54 eyes (79.6%). Of these 54 POAG eyes, FDT showed progressive deficits in 40 eyes (74.1%), whereas PERG amplitude P1N2 showed progressive deficits in 35 eyes (64.8%) before progression of field loss on SAP. A test battery consisting of SWAP and PERG P1N2-amplitude was able to detect 88.9% of eyes before a prediction of field loss on SAP. When comparing the results of the two functional tests, SWAP and FDT in the 84 eyes without progression of field loss on SAP between baseline and at 30 months, SWAP and FDT showed progressive deficits in 34.5% and 35.7%, respectively. CONCLUSIONS All three tests (SWAP, FDT, and PERG) have been successful in detecting glaucoma eyes with a future progression of standard visual field defects. A test battery of SWAP and PERG P1N2-amplitude improved the power to predict these progressive defects on SAP. It remains to be seen whether the long-term follow-up in POAG eyes will improve the false-positive rate of SWAP and FDT.

Detection of optic neuropathy in glaucomatous eyes with normal standard visual fields using a test battery of short-wavelength automated perimetry and pattern electroretinography

PURPOSE To evaluate the clinical use of a test battery of short-wavelength automated perimetry (SWAP), frequency-doubling technology (FDT) perimetry, and pattern-electroretinography (PERG) in patients with definite primary open-angle glaucoma (POAG) but normal results on standard automated perimetry (SAP). STUDY DESIGN Prospective, comparative, observational case series. PARTICIPANTS Thirty-six patients with POAG with standard visual field defects in one eye and normal standard visual fields in the contralateral eye and 36 normal controls were enrolled. MAIN OUTCOME MEASURES SWAP, PERG, FDT, and SAP were performed in all eyes, and global indices and amplitudes were used for statistical analysis. RESULTS When contralateral POAG eyes with asymmetric glaucomatous damage was compared, a paired t test showed significant differences in SAP mean deviation (MD) (P < 0.0001), SWAP-MD (P = 0.0003), FDT-MD (P = 0.0008), and PERG amplitudes (P < 0.0001). When comparing between POAG eyes with normal results on SAP and normal controls, Students t test showed significant differences for SWAP-MD (P < 0.0001), FDT-MD (P = 0.0006), PERG N1P1-amplitude (P = 0.0486) and P1N2-amplitude (P < 0.0001); receiver operating characteristic analysis revealed promising accuracy for SWAP-MD of 73.6% (P < 0.0001). SWAP-MD (P < 0.0001) and FDT-MD (P < 0.0001) correlated significantly with SAP-MD and with each other (range, P < 0.0001 to P = 0.0020). Regression analysis revealed that PERG P1N2-amplitude could improve the power of SWAP-MD from 73.6% to detect early POAG in eyes with normal results on SAP to an accuracy of 81.9%. CONCLUSIONS A test battery of SWAP-MD and PERG P1N2-amplitude could detect glaucomatous optic neuropathy in POAG eyes with normal standard visual fields, whereas FDT-MD and SWAP-MD significantly correlated with each other and with SAP-MD. All tests were able to detect the eye with the more severe glaucomatous optic neuropathy in patients with asymmetric POAG.

Comparisons of the amplitude size and the reproducibility of three different electrodes to record the corneal flash electroretinogram in rodents.

To compare corneal electrodes commonly used in rodent eyes for repeat and left versus right eye accuracy and variability to record the flash electroretinogram (ERG). Animals studied were eight C57BL/6 mice and eight rats of the Wistar strain. Scotopic ERGs were recorded from eyes of dark-adapted anesthetized rodents to compare a custom-made gold-wire contact lens electrode (CLE), a cotton-wick silver–silver chloride electrode (SCLE), and a coiled stainless steel wire electrode (SSE). Compared to SCLE and SSE, the potentials recorded by CLE are characterized by significantly larger ERG amplitudes and oscillatory potentials in both rats and mice (p<0.0001). In analyzing test–retest data comparing the three different electrodes the coefficient of variation was smaller (range, 10.3–15.5%) and the interclass correlation coefficient (0.77–0.93) showed a better agreement for the CLE. Recording scotopic ERGs with custom-made gold-wire contact lens electrodes records large amplitudes and shows a good reproducibility and reliability to monitor retinal function in rodent eyes.

Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents.

Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test-retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver-silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test-retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61-0.94) compared to the SSE (0.13-0.77), DTLE (0.02-0.69), and CSCE (0.12-0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.

Pilotstudie zu musterelektroretinographischen Veränderungen bei der DBA/2NNia-Maus Tiermodell eines angeborenen Engwinkelglaukoms

ZusammenfassungZielsetzung. Verlaufskontrolle der visuellen Funktion durch die Musterelektroretinographie (MERG) bei der DBA/2NNia-Maus, einem Tiermodell des Engwinkelglaukoms. Methoden. Bei 12 DBA/2NNia-Mäusen und 12 normalen C57BL/6-J-Mäusen wurden vom 2.–10. Lebensmonat musterelektroretinographische Potenziale mit verschiedenen zeitlichen und räumlichen Frequenzen abgeleitet. Ergebnisse. MERG-Ableitungen mit einer zeitlichen Frequenz von 7,5 Hz und einer räumlichen Frequenz von 0,4 Perioden/Grad zeigten die auffälligsten Unterschiede zwischen C57BL/6-J-Mäusen und DBA/2NNia-Mäusen. Im Vergleich zur normalen C57BL/6-J-Maus fanden sich bei der DBA/2NNia-Maus signifikante Amplitudenverminderungen ab dem 5. Lebensmonat (Students t-Test; p<0,01). Die Amplituden nahmen im weiteren Beobachtungszeitraum ab. Bei Studienbeginn betrug die mittlere MERG-Amplitude bei den DBA/2NNia-Mäusen 2,3±0,5 μV, im 5. Lebensmonat war diese um 0,9±0,45 μV reduziert (gepaarter t-Test; p<0,0001). Schlussfolgerungen. Retinaler Ganglienzellverlust konnte in früheren Studien bei der DBA/2NNia-Maus ab dem 6.–7. Monat nachgewiesen werden. Ab dem 5. Monat wurden musterelektroretinographische Veränderungen gefunden. Die Zusammenhänge mit dem Engwinkelglaukom beim Menschen sind viel versprechend für die Verwendung der DBA/2NNia Maus zur weiteren Glaukomforschung.AbstractPurpose. The aim of this study was to document the time-course of retinal dysfunction by pattern-electroretinography (PERG) in eyes of the DBA/2NNia substrain of mouse that develop an inherited angle-closure glaucoma. Methods. Twelve DBA/2NNia mice and 12 control C57BL/6 J mice were studied by PERG recordings from 2 to 10 months of age. PERGs were recorded using different spatial and temporal frequencies. Results. PERGs recorded with a temporal frequency of 7.5 Hz and a spatial frequency of 0.4 cycles/degree performed best to discriminate between DBA/2NNia mice and C57BL/6 J mice. When compared with normal C57BL/6 J mice, significant amplitude reductions of the PERG (Students t-test; p<0.01) were found in DBA/2NNia mice by 5 months of age and continued to decline as the animals aged. At beginning of follow-up, the mean PERG amplitude in DBA/2NNia mice was 2.3±0.5 μV. At 5 months of age, the mean PERG amplitude was reduced by 0.9±0.45 μV (paired t-test; p<0.0001). Conclusion. Previously, a significant loss of retinal ganglion cells was found in the DBA/2NNia mouse substrain at 6–7 months of age. In the present study, we found decreases in PERG amplitudes, occurring from the age of 5 months onward. Similarities with the findings in human glaucoma indicate the relevance of this animal model for further glaucoma research.