Glaucoma: a look back over the past twenty years
Over the past twenty years, in addition to the advent of a new technology for early diagnosis, treatment of glaucoma has undergone fundamental developments thanks to the performance of various multi-centre studies that have enabled more precise identification of the risk factors associated with the appearance of the disease and its development. This article details all these elements and comments on study results, progress made with new diagnostic procedures and the perfecting of existing procedures with the introduction of new drugs, the development of new lasers and the improvement of surgical techniques.
Over the course of the last third of the 20th century, glaucoma acted as the driving force for progress in ophthalmology, in spite of the advent of phacoemulsification, which stimulated cataract surgery and the arrival of the Excimer laser, which transformed refraction surgery and which, for the general public, ignorant as it was of knowledge of the specialty, represented a real revolution. As experts, we were indeed conscious of the fact that public perception saw only the tip of the iceberg because, in the places where the reality of the progress made was truly understood, glaucoma unquestionably retained its star position.
In 1979, in the preface to our book, Traitement du glaucome (The Treatment of Glaucoma) we wrote that progress made over the past two decades due to glaucoma was such that if the disease had not existed, ophthalmology would have had to invent it: this sentence is still true today, thirty years later.
Clearly the transformation that has taken place over these past 20 years has represented a revolution whether in terms of means of exploration, medical treatment, surgery or patient monitoring. Even the definition itself of the disease has been changed in view of the progress made with prospective studies over these past twenty years, which has consolidated certain concepts and provided us with increasingly efficient instruments to ensure more efficient treatment and monitoring as well as the use of greater resources to improve patient compliance.
At the end of the eighties, glaucoma diagnosis was based almost exclusively on the visual field, gonioscopy, ophthalmoscopic study of the optic papilla and tonometry. For monitoring, developments in the visual field can be added, along with supervision of alterations to the optic papilla by means of retinographies in series and, in the best cases, planimetry or stereopsy, all based on subjective analysis by experts who, when looking at the same case, all gave very different answers. We were lacking, therefore, sufficiently efficient objective procedures for diagnosis and monitoring, which prevented us (except in the case of an expert) from taking charge of a patient with glaucoma with a guarantee of success.
As for medial treatment, we continued to depend almost exclusively on the beta blockers developed in the sixties and on the diuretics of the previous decade. For surgery, with the exception of trabeculectomy, which was also developed in the sixties, the other surgical techniques dated from the 19th century.
The myth of ocular hypertension-glaucoma and above all clarification of the risks/benefits ratio of submitting a patient with hypertension to non-discriminatory treatment was brought about thanks to analysis of the results of the OHTS study (Ocular Hypertension Treatment Study) (1), which identified and quantified the risk factors involved in the development of ocular hypertension into glaucoma. It was thus possible to develop risk calculators in order to facilitate the work of the ophthalmologist and enable the patient to gain a better understanding of the scale of his pathology and therefore take a joint decision with the doctor in terms of possible treatment. Thus, the decision to begin treatment is based on the presence, or not, of factors such as age, excavation/papilla ratio (C/D) and central corneal thickness. A decisive contribution was also made to the design of quantitative assessment techniques for new lesions of the nerve fibre layer (GDx, OCT), alteration of the visual field thanks to new campimetric strategies (TOP, SITA, blue/yellow perimetry, frequency duplication perimetry, flicker perimetry, etc.) and early alterations of the papilla (HRT3,OCT,RTA). All of this progress took diagnosis ahead by at least five years compared to the traditional 20 year old systems.
Medical treatment of glaucoma aims solely to preserve vision, such that developments in the loss of retinal ganglion cells are comparable to the rate of loss in a normal person of the same age; this was established fundamentally thanks to the EMGTS (Early Manifest Glaucoma Trial) (2), CIGTS (Collaborative Initial Glaucoma Treatment Study) (3) and AGIS (Advanced Glaucoma Intervention Study) (4) studies. Thanks to these studies we know that target pressure (theoretical intraocular pressure to be achieved to ensure that the disease does not develop further) will be defined by a range of factors such as age, life expectancy, the development stage of the glaucoma and the presence or absence of other associated risk factors. This enabled us to discover that advanced glaucoma requires lower levels of pressure than glaucoma in the early stages, as well as long life expectancy or low pressure at the time of diagnosis, contrary to short life expectancies and very high initial intraocular pressure readings, that do not in general require such a strict threshold in terms of the target pressure [1, 2, 3, 4, 5].
The aims of medical treatment over these past twenty years have been directed in part towards research into the most powerful drugs with the least side effects and a simpler posology. At the beginning of the nineties, Brimonidine (1991) came on the scene, representing progress in the alpha-agonist group, even though no definite results had been achieved with it when it first arrived 10 years previously. At the time topical carbonic anhydrase inhibitors were being developed (dorzolamide in 1991 and brinzolamide in 1998). The greatest success was achieved with prostaglandins with, to begin with, Latanoprost (1992), Bimatoprost (1997) and Travoprost (1999) the added value of which lies in the extension of the hypotensive effect beyond 24 hours, which meant that for the first time a once a day only drug was available, ensuring better patient compliance.
Over this past decade the appearance of fixed therapeutic combinations has been another means by which to improve patient compliance. Clearly around 50% of patients need at least two active principles to contain glaucoma at an adequate level and it is certain that compliance is considerably reduced when the patient has to apply eye drops several times a day. The logic of combining two drugs in a single product represented a decisive step forward, something which has been confirmed by all the studies undertaken to check this objective without any loss of therapeutic efficiency. The combination of beta blockers and prostaglandins, carbonic anhydrase inhibitors and alpha-agonists, has enabled a large number of patients to follow their treatment more easily, a fact that has certainly improved their quality of life since they depend less on fixed times for applying eye drops.
The number of anti-glaucoma surgical operations performed worldwide has fallen by 50% over these past ten years. This reduction can be explained mainly by the arrival of numerous drugs over the preceding decade which, as we have said, enabled the treatment of numerous cases previously condemned to surgery. Nevertheless this has not stopped surgical techniques from progressing because unfortunately the number of cases for which medical treatment is not sufficient to slow progress remains high. Argon laser trabeculoplasty (ALT) has improved, at least in terms of facility of application but not in terms of results, due to the development of selective trabeculoplasty (SLT) (Latina 1995) [6], which has developed over the past ten years. As for surgery itself, the old Krasnov technique, dating back to 1963 [7] is still in use, taken up by Zimmermann (non-penetrating trabeculectomy) in 1984 [8] and improved by Stegmann (Viscocanalostomy) in 1995 [9] and Mermoud (deep, non-penetrating sclerectomy) in 1996 [10].
Surgical innovations have been completed by the advent of microvalves or micro-bypasses (iStent), introduced into the Schlemm canal by a corneal micro-incision that opens up direct communication with the anterior chamber though which circulates the aqueous humour and valves opening up communication between the anterior chamber and the suprachoroidal space (Gold Shunt).
Destructive surgery of the ciliary body is reserved for cases where all attempts at stabilisation have failed, and this technique was also improved greatly thanks to diode laser transscleral cyclophotocoagulation in 1996 [11].
Finally ultrasound biomicroscopy (M), has revealed the pathogenic mechanisms of certain forms of glaucoma as well as providing a better understanding of how surgery works and the reasons for failure. [12].