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A Double-Masked Study of Timolol and Pilocarpine Combined: Reply
370
AMERICAN JOURNAL OF OPHTHALMOLOGY
There is no doubt that a combined prepara tion of timolol and pilocarpine may improve compliance. However, in order to prove its efficacy, it should be compared not only to pilocarpine alone but also to timolol alone. ORNA GEYER, M.D. MOSHE LAZAR, M.D. Tel Aviv, Israel
Reply EDITOR: In our study, the intraocular pressure mea surements of the patients receiving the timolol-pilocarpine combination drug twice a day were lower than the intraocular pressure measurements of the group receiving pilocar pine alone four times a day. Therefore, the combination drug was more effective in low ering intraocular pressure than pilocarpine alone. Doctors Geyer and Lazar point out that this new combination drug should also be com pared to timolol alone. Results of such a study have been reported recently by Hevding and Aasved. 1 They found that the timolol-pilocarpine combination drug admin istered twice a day regulated intraocular pres sure better than timolol eyedrops alone. Ad ditionally, their results showed that the additional effect of pilocarpine was detectable 12 hours after drop administration. P. JUHANI AIRAKSINEN, M.D. RISTO VALKONEN, M.D. TAPIO STENBORG, M.D. Oulu, Finland KIRSTI TAKKI, M.D. Lohja, Finland ANNELI KLEMETTI, M.D. Jyvaskyla, Finland MATTI KONTKANEN, M.D. PERTH OSKALA, M.D. Savonlinna, Finland
Reference 1. H0vding, G., and Aasved, H.: Timolol/ pilocarpine combination eye drops in open-angle glaucoma and in ocular hypertension. A controlled randomized study. Acta Ophthalmol. 65:594, 1987.
September, 1988
Irregular Pupil Cycling as a Characteristic Abnormality in Patients With Demyelinative Optic Neuropathy EDITOR: In the article "Irregular pupil cycling as a characteristic abnormality in patients with demyelinative optic neuropathy" by J. G. Milton, A. Longtin, T. H. Kirkham, and G. S. Francis (Am. J. Ophthalmol. 105:402, April 1988), the authors used a highly sophisticated method to point out that irregular pupil cy cling is specific in demyelinative disease. They state that this phenomenon is not caused by fatigue-like visual characteristics, but caused by prolonged latency of the pupil lary reflex concerned with transmission pro longation in demyelinated fibers. They listed two reasons: the absence of progressive dimi nution, and the different time course with pu pillary fatigue. In general, the output signal of the negative feedback system will oscillate when the feed back gain is too high. Pupillary oscillation in duced by artificial increase of the system gain is one example. The oscillation occurs with the frequency where the transfer function of the system shows 180-degree phase lag. If the gain at this frequency is greater than unity, oscillation continues. Transmission prolonga tion of the system enlarges phase lag and then reduces the oscillation frequency. How ever, at the lower frequency, the pupillary gain is higher in this frequency region. 1 This means that the delay of transmission cannot disturb the continuous oscillation. Only ab normal reduction of the gain causes cessation of the cycling. Progressive gain reduction can be called a "fatigue-like phenomenon," whereas the gain reduction itself may be in volved with difficulties of transmitting higher firing rates (unpublished data). I studied artificial control of feedback gain of the pupillary system using a method simi lar to that of the authors. The stimulus inten sity, however, was continuously changing proportional to the reciprocal of the pupillary area, and the area of the pupil was measured with a silicon vidicon. The vidicon had an afterimage and then increased the latency of the feedback loop. In normal subjects, regular cycling could be obtained up to 0.7 Hz. While the feedback technique may detect response delay, in order to measure progres sive gain decrease, one need not apply feed-
AMERICAN JOURNAL OF OPHTHALMOLOGY
There is no doubt that a combined prepara tion of timolol and pilocarpine may improve compliance. However, in order to prove its efficacy, it should be compared not only to pilocarpine alone but also to timolol alone. ORNA GEYER, M.D. MOSHE LAZAR, M.D. Tel Aviv, Israel
Reply EDITOR: In our study, the intraocular pressure mea surements of the patients receiving the timolol-pilocarpine combination drug twice a day were lower than the intraocular pressure measurements of the group receiving pilocar pine alone four times a day. Therefore, the combination drug was more effective in low ering intraocular pressure than pilocarpine alone. Doctors Geyer and Lazar point out that this new combination drug should also be com pared to timolol alone. Results of such a study have been reported recently by Hevding and Aasved. 1 They found that the timolol-pilocarpine combination drug admin istered twice a day regulated intraocular pres sure better than timolol eyedrops alone. Ad ditionally, their results showed that the additional effect of pilocarpine was detectable 12 hours after drop administration. P. JUHANI AIRAKSINEN, M.D. RISTO VALKONEN, M.D. TAPIO STENBORG, M.D. Oulu, Finland KIRSTI TAKKI, M.D. Lohja, Finland ANNELI KLEMETTI, M.D. Jyvaskyla, Finland MATTI KONTKANEN, M.D. PERTH OSKALA, M.D. Savonlinna, Finland
Reference 1. H0vding, G., and Aasved, H.: Timolol/ pilocarpine combination eye drops in open-angle glaucoma and in ocular hypertension. A controlled randomized study. Acta Ophthalmol. 65:594, 1987.
September, 1988
Irregular Pupil Cycling as a Characteristic Abnormality in Patients With Demyelinative Optic Neuropathy EDITOR: In the article "Irregular pupil cycling as a characteristic abnormality in patients with demyelinative optic neuropathy" by J. G. Milton, A. Longtin, T. H. Kirkham, and G. S. Francis (Am. J. Ophthalmol. 105:402, April 1988), the authors used a highly sophisticated method to point out that irregular pupil cy cling is specific in demyelinative disease. They state that this phenomenon is not caused by fatigue-like visual characteristics, but caused by prolonged latency of the pupil lary reflex concerned with transmission pro longation in demyelinated fibers. They listed two reasons: the absence of progressive dimi nution, and the different time course with pu pillary fatigue. In general, the output signal of the negative feedback system will oscillate when the feed back gain is too high. Pupillary oscillation in duced by artificial increase of the system gain is one example. The oscillation occurs with the frequency where the transfer function of the system shows 180-degree phase lag. If the gain at this frequency is greater than unity, oscillation continues. Transmission prolonga tion of the system enlarges phase lag and then reduces the oscillation frequency. How ever, at the lower frequency, the pupillary gain is higher in this frequency region. 1 This means that the delay of transmission cannot disturb the continuous oscillation. Only ab normal reduction of the gain causes cessation of the cycling. Progressive gain reduction can be called a "fatigue-like phenomenon," whereas the gain reduction itself may be in volved with difficulties of transmitting higher firing rates (unpublished data). I studied artificial control of feedback gain of the pupillary system using a method simi lar to that of the authors. The stimulus inten sity, however, was continuously changing proportional to the reciprocal of the pupillary area, and the area of the pupil was measured with a silicon vidicon. The vidicon had an afterimage and then increased the latency of the feedback loop. In normal subjects, regular cycling could be obtained up to 0.7 Hz. While the feedback technique may detect response delay, in order to measure progres sive gain decrease, one need not apply feed-