Konservative katarakttherapie in klinik und experiment

Abstract

Up to the beginning of the 17th century it had been the general belief that a cataract results from the formation of a whitish membrane in the pupil. The first authors who dared to call cataract an opacity of the lens itself were either laughed at or violently attacked. Only after the studies of brisseau (1709) the true nature of cataract became evident. The therapeutic consequence was the development of cataract extraction (daviel, 1753). Surgery became the universally applied way of treatment, while conservative therapy was more or less neglected. Nevertheless, prevention and healing of cataract through drugs has always been a favorite object of ophthalmology.

Principal objections, however, have repeatedly been raised against medical treatment of cataract. Time and again it was doubted that lens opacities could be influenced at all. Even believers in a medical cataract treatment disagreed on the question, whether opacities could actually be cleared or only their progress be prevented.

becker (1877) gave important impulses for non-surgical therapy. He considered a disturbed nutrient supply of the lens due to senility a possible cause for opacities. Although becker himself was not in favour of a drug therapy for senile cataract, his theory encouraged many others to develop ways of medical treatment. vogt (1931–1942) on the other hand believed nonsurgical treatment to be Utopian, because the onset and development of cataract depended on heredity. He saw his theory confirmed by follow-up studies in identical twins. These opposing approaches of becker and vogt — characterized best by the catchwords senility ”and heredity” — were the ground for endless discussions on the justification of therapeutic efforts. Today they are no longer a matter of dispute. vogt's theory of a genetic preformation of senile cataract could not be substantiated, though several types of opacities could be determined as being hereditary conditions. At any rate, vogt was wrong to believe, that hereditary diseases could not at all be treated with drugs. Although to date a conversion of the genotype does not yet seem possible, it is well known, that a manifestation of the phenotype can be influenced by drugs. This drug treatment of cataracts is not principally impossible, even in cases of genetic origin.

All major medical achievements of the last century have somehow been introduced in the therapy of senile cataract. During the age of pioneer work in physiological optics, for instance, it was assumed that accomodative stress was the cause of lens opacities. schoen (1887–1889) believed to have found histological evidence backing this theory and tried to prevent cataracts by exact correction of refractive errors.

A next step in cataract therapy was the use of inorganic substances. Here potassium, calcium, magnesia, strontium, mercury and cerium were applied in the form of iodide, iodate, nitrate, acetate, citrate, cyanide, lactate, chloride, or chlorate. These substances were supposed to work through substitution of inorganic lens constituents, dehydration of the lens, systemic effects on the organism, or increased blood supply to the eye.

Also some organic substances owe their temporary popularity in cataract therapy to an effect on the blood circulation. Dionine, boric acid, glycerine, papaverine, parotin, tetranitol, niacin, and procain were favourites. An evaluation of their influence is, however, complicated by the fact, that an increased blood supply would not be limited to the ciliary body. It could also increase the blood supply to the macula, thus improving visual acuity without affecting the lens.

Fortunately, radium was only used for a short period in cataract therapy. As soon as its true effect on the lens became generally known, the method was abandoned.

Immunotherapy as a form of cataract treatment was largely propagated by römer (1905–1914). In his opinion cataract had to be considered an autoimmune disease due to so-called lentotoxins. His method to intercept such toxins in the blood stream was to apply lens protein orally. Though römer himself soon abandoned this theory, others used his procedure in several modified ways and applied homologous and heterologous lens proteins parenterally and orally. davis (1922–1937), on the other hand, recommended the use of lens antigens in the place of antibodies.

First experiments with hormones were initiated when the importance of the endocrinium for aging organisms became known. One of the first scientists in this field was siegrist (1928). Interest in the hormone therapy was increased by the fact that several diseases of the endocrinium are complicated by cataracts. Although it has been possible to delay the progress of endocrine cataracts by substituting a lacking hormone (e.g. insulin, parathormone) senile cataracts could not be influenced in this way. The name endocrine cataracts” — much popularized by these futile therapeutic attempts — is, however, misleading. On the one hand, the so-called endocrine cataracts are due to totally different causes, while on the other hand there are non-endocrine cataracts of similar etiology (e.g. due to galactose and xylose or to hypocalcemia of non-endocrine origin.) A classification as sugar cataracts and hypocalcemic cataracts is more up to the point. Up to now, nearly all known hormones, — parathormone, insulin, parotin, and even corticosteroids — have been tested in cataract therapy, mostly in polyglandular” form.

The next period in non-surgical cataract therapy was that of the vitamins. This seemed to be a rather promising procedure, as vitamin defiencies had been discovered to be the cause of various diseases. However, the search for a specific lens vitamin, for a cataract-preventive-factor”, proved futile. Special importance was attached to vitamin C, because the lens turned out to have the highest concentration in ascorbic acid next to the adrenals, and because several authors found a decrease of vitamin C in opaque lenses. Although a cataract due to vitamin C deficiency alone could not be detected, it was possible to show that a scurvy could be an additive subliminal factor promoting the action of other cataractogenics. Further experiments were made with the vitamins B₁, B₂ -complex, riboflavin, niacinamide,B₁₂,D,A,E, and P.

Ascorbic acid and riboflavin caused considerable interest being redox-systems. Further knowledge, that an intact and efficient redox-system is essential for maintaining the lens metabolism became important in cataract therapy. Among other SH-substances cysteine and glutathione were given special attendance. They were not only tested for their use in senile cataract, but also for their applicability in the prevention and treatment of irradiation cataracts.

New impulses to drug treatment were given by ogino (1955–1957). He was able to show the cataractogenous effect of various quinones. This led to the development of substances intended to act as competitive inhibitors of pathogenic quinones, without inducing opacities themselves. ogino's theory on the overall importance of quinones in cataractogenesis could not be verified. In some types of opacities, however, an influence of such compounds seems likely (e.g. naphthalene).

All of these attempts were aimed at influencing either the lens directly or its surrounding tissues, There exist, however, other forms of treatment meant to affect systemic diseases which are complicated by cataracts, such as the treatment of diabetes with insulin, of galactosemia with lactose-free diet, or of hypoparathyroidism with parathormone, calcium or AT 10. Experiments on radiation cataracts made obvious that, — aside from therapy — prophylaxis can be of superior importance. The latter can consist in the elimination of cataractogenic factors or the development of protective agents.

Up to now, drug treatment of senile cataract was only in part based on biochemical analysis. If certain constituents of the lens were found to be at a decreased level, it was tried to raise their intake by drug application. We have seen numerous examples of such a procedure and have to point out that an administration of missing substances is not sufficient, as long as their concentration at the site of action and their part in metabolism cannot by exactly determined.

Today it is evident that the lens transparence is based on intact biochemical processes which are of a rather complex nature. Ophthalmic experimentation has revealed various factors which might disturb these processes and induce lens opacities. Analyses of the lens metabolism in cases of cataract have shown that disturbances of the carbohydrate metabolism may be the primary cause, although the opacity itself is a secondary reaction of the lens proteins to these disturbances. The importance of the intermediary metabolism for a tissue — especially that of the carbohydrates — lies in the energetic balance of endergonic and exergonic processes. Because of their complex interrelations, disorders of the energy balance can effect different lens constituents.

In many experimental cataracts it has been possible to elucidate the mechanism of such disorders as well as their effects. It could be shown that the kind and proportion of the lens hazard is related to the age of the animal. We feel that this point is of great importance for future experiments on drug treatment of senile cataract.

In most cases senile cataracts are due to aging processes in lens metabolism accompanied by a disturbance of the energy balance. In contrast to the aforementioned experimental disturbance factors, aging is no sudden incident, and not only the individual lens fibre is affected. According to h. k. müller, the process of lens aging is closely related to alterations in the surrounding media.

Many biochemical studies on the lens have considered age changes of metamolism. Experimentation mostly involved lenses of animals. As nordmann recently showed in a critical review of the literature, our knowledge on age changes in human lenses is rather limited. With certain reservations, however, the results obtained with test animals may well be applied to conditions in the human lens. Here too, the carbohydrate metabolism plays an important role in the energy balance and is subject to considerable age changes. A decrease in intensity of metabolic processes can be observed and narrowings and blockages of the pathways of glucose breakdown are known to occur.

These disturbances might be due to reduced enzyme reactions. They interfere with the final steps of the carbohydrate breakdown, which are responsible for energy supply. A decrease in certain enzyme activities, however, does not necessarily induce metabolic decompensation. In the complex mechanism involved, bypaths may compensate the negative effects of a blockage. If the reason behind biochemical studies on lenses is to find a way of treating cataracts with drugs, our first step must be to investigate the age dependence of the metabolic pathways of carbohydrates. A detailed evaluation of the capacity of the single pathways is as necessary as investigations on how to increase this capacity. Results in this field might show the way in which the metabolic conditions in the aging lens can be influenced favorably.

So far, satisfying results of a non-surgical therapy were seen in diabetic, galactosemic, and tetanic cataracts. They are due to a treatment of the basic disease. In senile cataract we might call the basic disease” a gradually decreasing energy yield through the carbohydrate breakdown. It is our opinion that this age dependent decrease in energy supply might at least be partly influenced by activating metabolic bypaths of the carbohydrate breakdown.

Thus the aging lens would be in a better condition to withstand onset and progress of opacities.