|Year : 1979 | Volume
| Issue : 4 | Page : 71-75
Medical treatment of primary glaucoma
Universitats-Augenklinik, Joseph- Schneider-Strabe 11, 8700 Wuerzburg, FRG
Universitats-Augenklinik, Joseph- Schneider-Strabe 11, 8700 Wuerzburg, FRG
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Leydhecker W. Medical treatment of primary glaucoma. Indian J Ophthalmol 1979;27:71-5
| A. Acute angle block glaucoma:|| |
Medical treatment of the acute angle block glaucoma serves only as preparation for surgery which is the treatment of choice after the relief of the attack. First phase of standard treatment consists of weak miotics (Pilocarpine 0.5% 6 x) which are better than strong miotics as these could increase the pilpiilary block. To this are added: 750 mg. Acetazolamide orally or i.v. and a sedative for which we found 0.2 cl brandy very useful in lowering the i.o. pressure. If the i.o. pressure does not start to come down within 3 hours, we give glycerol (1.2 ml/kg body weight) or 250 ml mannitol 20% i.v. If the attack still persists after 6-1C hours, I would operate upon without further delay (peripheral iridencleisis with iridectomy).
| B. Chronic simple glaucoma:|| |
Medical treatment of the primary chronic forms of glaucoma must be modified according to the individual case. I shall first discuss some general guide lines, continue with the difficulties of treatment, new drugs and finally summarize some frequent mistakes.
When to start medical therapy: The medical therapy is started when the mean i.o. pressure is 25 mmHg or more and if treatment reduces the i.o. pressure considerably. Any action or delay is based on an estimate of probable risks. The risk of starting treatment with i.o. pressure around 25 mmHg is that some ocular hypertensives will be treated unnecessarily. In eyes in which the i.o. pressure does not respond significantly to miotics, I would not prescribe them. The risk of waiting, on the other hand, is the patient will usually not come back for regular checks over years until the optic nerve is partly destroyed. The chances for the future are slim when treatment is started after parts of the field have gone and the optic nerve is showing partial atrophy.
When not to start medical therapy: In patients aged 80 years or over I would not treat ocular hypertension if it had been evidently tolerated for this length of the time without damage to the optic nerve. No treatment is given if the i.o. pressure is not considerably lowered by miotics as is the case in ocular hypertension, hydrophthalmia or glaucoma without hypertension, and in some secondary glaucomas (e.g. glaucoma with aniridia or with irido-corneal dysgenesis). It is also of little use to give miotics if a patient is not able to apply the drugs e.g. because he cannot pay for them as may be the case in developing countries or because he forgets to apply them because of cerebral sclerosis, or he will not apply them correctly because of shaky hands or bad vision resulting from the use of miotics. Finally, miotics must not be given if they increase the i.o. pressure as in malignant glaucoma or in other forms of lens induced secondary glaucoma or in hemorrhagic glaucoma.
No prophylactic treatment is given in normotensive eyes. Some doctors do so, if for any reason the patient is believed to have had previously increased i.o. pressure. Then they give pilocarpine once a day, but this drug is effective only for 6 hours approximately. In case an eye is to be treated, pilocarpine must be applied at intervals not longer than 6 hours during daytime. So application only once a day is worse than giving no treatment at all.
Normalization of the i.o. pressure is the aim of medical therapy. The doctor's task is to find out the weakest drug which normalises the i.o. pressure in each patient. Normalization means keeping the i.o. pressare below 20 mmHg throughout the 24 hours. One must realize that 20 mmHg signifies the 2 sigma limit of normal distribution of pressure. It is not necessary to start treatment in each eye which only just surpasses this limit, but once it has been decided to prescribe drugs, one should try to reduce the pressure to below 20 mmHg. Thus we have some allowance for occasional increase of pressure due to the stress of daily life. Any such number is only an average, since there are eyes which would tolerate a higher i.o. pressure and other eyes for which 20 mmHg is too much. We cannot know this individual limit of tension tolerance before damage occurs. If we want to be on the safe side, 20 mmHg seems to be an acceptable limit.
The technique of pressure normalization:
For the first prescription of miotics 12 tonometries are necessary, i.e. at least 3 tonometries on each of 4 days. Tonometry is preferred at the suture points of daily treatment. If a patient applies drops 3 x a day at 7, 12 and hrs, and in addition once before sleeping at 22 or 23.00 hrs., the check should start before application of the 7 o'clock drops. This will check the effect of the evening drops or ointment, and will answer the question whether they are sufficient to normalize the pressure until the morning. After tonometry at 7, the 7 o'clock drops are then applied and pressure is checked again just before the noon drops are given. Again tonometry is performed just before the 5 p.m. drops. I have shown previously that at least 4 such days with 3 tonometries each day are required to be sure that the i.o. pressure is controlled.
Supervising pressure normalization: After the first regulation has been done in this way, further checks of tension are necessary every 4-6 weeks in alternating way, so that e.g. in January the check is done between 7 and 8 a.m., February at noon and March at 5 p.m. Morning checks are more important than afternoon measurements. Frequently made mistakes are:
(1) to have the patient come back for a check either some 2 hours after he has applied the drops, in which case a normal pressure does not mean that it is really regulated,
(2) to check 10 or more hours after the last application, in which case a pressure above 20 rnmHg does not signify that treatment is insufficient, and
(3) to check only in the afternoon.
This scheme applies of course to the usual 4 x daily treatment only. It must be modified according to other rhythms of application. If a drug is given twice daily, e.g. betablockers. or once a week (e.g. Ocusert) checks must be done just before each application.
In any case we have to convince ourselves in each individual that his medical treatment is sufficient by measuring repeatedly at the suturing point of therapy.
Miotics: Pilocarpine 0.5-2.0% 3 x daily and for the night an oily solution or an ointment will normalize the i.o. pressure in approximately 60% of simple glaucoma cases over a period of years. Stronger solutions are not more effective. Aceclidine is an alternative. Neostigmine 1-3% or Carbachol 1-3% are usually stronger. Eserine 0.25% often irritates and is therefore not in my list. I never give stronger miotics in phakic eyes, such as demecariumbromide, phospholin-iodide or DFP. Combinations of miotics are no better than each of the single component they comprise, and should therefore not be prescribed.
Sympathicomimetics: Even the weak miotics which I have just mentioned can cause considerable discomfort. In the young patient accommodative myopia can be intolerable and in all ages the miosis with bad vision in dim light, a local irritation, allergy, iris cysts, and in prolonged use iritis can be most annoying. Epinephrine by itself is often insufficient for the normalization of i.o. pressure and must not be given in eyes with a narrow angle. In wide angle glaucoma the combination of miotics with epinephrine preparations can often relieve the discomfort caused by miotics alone, but they have other side-effects, such as tachycardia, extrasytoles, rise in blood pressure or black deposits on the conjunctiva and cornea consisting of adrenochrome, or a macular degeneration especially in aphakia.
Ocusert can give a constant and low concentration of pilocarpine in the ocular tissues. This is therefore, a very useful way to apply pilocarpine to patients under the age of 55.
Dipivalylepinephrine is 10 x more active than the usual preparations of epinephrine, so that clinically only 1/10 of the dose is required which will not cause side-effects. Radioactive studies reveal that only 3-5% of a locally administered drug penetrates into the eye. The major part of the drug in each application is non-beneficial. It can exhibit local irritation or systemic side-effects. Problems encountered in that phenomenon are especially relevant to the sympathomimetic concepts of open-angle glaucoma therapy due to the "sandwich-architecture" of cornea with its change of lipophilic and hydrophilic layers. The permeability of a drug through the cornea. can ba improved by changing its biophysical properties. Epinephrine chloride or borate is a rather hydrophilic compound compared to the lipophylic compartments of the cornea. Dipivalylepinephrine is a "prodrug", a drug undergoing biotransformation prior to exhibiting the pharmacological action. It is more lipophilic while maintaining some hydrophilicity. In enters the eye more easily than traditional epinephrine preparations. In a double-blind-test we applied on one eye epinephrine 1%, on the fellow other eye of the same patient DPE 0.025%, 0.1% or 0.25%. Both eyes had applanation tonometry done for 8 hours after application of the drops. It was found that DPE 0.1% was as effective as epinephrine 1%, while DPE 0.025% was less and DPE 0.25% more effective than epinephrine 1% (Kriegelstein.
Beta-blockers are a new field in medical treatment of glaucoma. We tested in our hospital, Bupranolol in an oily solution (Ophtorenin) and Timolol. After the first application both drugs cause a fall of the i.o. pressure of 40-60%. The 0.5% Bupranolol free base in an oil solution is treated very well. After the first application the i.o. pressure drops by 50-60% and even after 24 hours the original pressure is not fully regained. The fall in intra ocular pressure is as much as 40-60% of the original i.o. pressure. The systolic or diastolic blood pressure is not affected. There is a local anaesthetic property on the eye lasting up to 15 min., but there is no effect on tear flow. Timolol has a very similar effect after the application as 0.1-0.5% eye drops. This effect of the first application can be used for example, if a low pressure is required for cataract extraction in a glaucomatous eye. After a few days of continued application the effect becomes less so that a reduction of the intra ocular pressure of only 20% persists. Both drugs, Bupranolol as well as Timolol, are much less effective after a few days, and this type of tachyphylaxis originating from one of the drugs applies to the other drug, although this one has not been used before on that eye.
These drugs have the advantage of showing influence on the pupil or on the accommodation. They are given only twice daily. At present it would appear that the percentage of pressure decrease is higher in early glaucoma than in long standing glaucoma, especially if that eye has been treated before with adrenaline preparations. The facility of outflow is not changed significantly. We suppose, therefore, that Bupranolol or Timolol decrease the formation of aqueous humor.
Clonidine. While the beta-blockers act on the formation of aqueous, the stimulation of alphareceptors by Clonidine decreases the intra ocular pressure by causing a better facility of outflow. This drug also lowers the pressure by 20% and has no side-effects in concentrations of 0.125%. Stronger solutions than that should not be given since they will lower the general blood pressure. This would decrease the perfusion pressure of the disc and may cause a deterioration of the visual field. In internal medicine this drug is used in hypertension.
Bencyclane with digitalis. Finally a type of treatment shall be mentioned which is frequently neglected. Vasodilators combined with digitalis. A double-blind study has shown that in eyes with a normalized intra ocular pressure the deterioration on the field with this treatment was stopped and that sometimes lost parts of the field can be regained after oral treatment with digitalis and bencyclane, a drug which not only dilates blood vessels but in addition alters the aggregation of thrombocytes.
Mistakes. Some frequently made mistakes in medical treatment have been mentioned above, and need only be summarized here. They are:
- to delay treatment until the field shows deffects
- to give insufficient treatment without lowering the intra ocular pressure to below 20 mmHg throughout the 24 hrs.
- prescribe miotics without 12 checks of the effect on each individual for the first normalization and later to check less often than every 4 weeks
- to check shortly after the patient has applied the drops instead of at "suturing points"
- not to note the day, the time and the interval since the last application. Any statement of a pressure without these data give little information
- not to discuss with the patient discomfort caused by the drops
- not to check that the patient has the appropriate technique of application
-- to let the patient wait who comes for a check tonometry only to be impolite to the patient
Patients must be willing and able to take their drops. They must understand their disease, as in diabetes or in kidney dialysis.
If these mistakes are avoided, if the weapons which we have against glaucoma are used and carefully applied, the patient stands a very good chance to stopping his disease and any further loss of field. To some extent one can say that the prognosis of simple glaucoma is as good as the specialist who treats it.
| References|| |
Leydhecker W., 1973, Glaukom in der Praxis , 2,
Aufl. Springer Heideiberg, 178, 868.
Leydhecker W., Is a medical therapy of glaucomatous field defects possible? Results of a double blind study. Recent Advances in Glaucoma. Intern. Glaucoma Symposium, Prague 1976. Ed. S. Rehak M.M. Krasnov, G.D. Paterson. Avicenum, Prague/Springer-Verl. Berlin-Heidelbeg, New York 1977 S. 183.