“UNTIL THE MIDDLE OF THE 19TH CENTURY THE LIKELIHOOD THAT
AN INDIVIDUAL WOULD BE BENEFITED FROM AN ENCOUNTER WITH A PHYSICIAN
WAS ABOUT 50%.”
THIS OLD STATEMENT IS STILL NOT FAR FROM THE TRUTH.
IMPLICATIONS FOR APPROACHES TO TREATMENT TODAY
Clive Migdal MD FRCS FRCOphth
Western Eye Hospital
London, UK
The world in the 1850`s was very different from the world today.
Medicine was very different, as was the practice of ophthalmology.
Helmholtz discovered the ophthalmoscope in 1851, and within 10
years, improved models were in use throughout the world. Also
in the 19th century, when modern ophthalmology was beginning,
Wardrop and Dalrymple were initiating studies of the gross pathology
of the eye, as good microscopes became available. By integrating
the study of clinical and pathological aspects of diseases of
the eye, improved understanding of pathogenesis and possible treatment
options resulted.
Today we have additional and sophisticated tools to carry out
the examination of the eye, although we still rely on basic features
such as the intraocular pressure measurement and the appearance
of the optic disc and field on which to base our management of
the glaucoma patient. In addition, modern treatment options include
effective (and expensive) new drugs, laser procedures and sophisticated
microsurgical techniques. But are our patients better off? Treatment
for this chronic disease now needs to be effective for a longer
period of time as the life expectancy of the patient has now increased.
Also, demands of the modern world make individuals more aware
of the possible adverse effects of treatment on the quality of
life.
History of glaucoma therapy:
The early history of the treatment of glaucoma is centered on
three events: (1) the discovery of the curative action of iridectomy
in certain glaucomas, (2) the development of filtering operations,
and (3) the discovery of the first ocular hypotensive drugs (eserine,
pilocarpine and epinephrine).
Von Graefe (1828-1870) first reported on iridectomy in glaucoma
in 1857. His iridectomy for glaucoma was a broad, but not necessarily
basal , excision of the iris through a scleral incision without
a conjunctival flap. He believed that removal of iris tissue per
se lowered intraocular pressure (IOP). Von Graefe candidly admitted
that he had no clear idea of the mechanism underlying this effect.
The results of iridectomy were summarised in 1907: `the success
of the iridectomy depends on two factors: the type of the glaucoma
and the stage of the disease`, and goes on to state that `vision
lost before the operation returns only partially; this return
is only minimal in cases with pupils that are no longer reactive
to miotics or far advanced excavations and whitish gray discoloration
of the disc`. These statements remain true even today.
The history of usefulness of Graefe`s iridectomy is closely linked
to the history of filter operations. De Wecker (1832-1906) originated
the term `filtering` procedure with the idea that, in the presence
of IOP, properly executed corneoscleral incisions can heal in
a way that allows intraocular fluid to `filter` out of the eye.
He initially advocated sclerostomy as an `auxilliary` or `substitute`
for iridectomy. Shortly after the turn of the century, the operation
lost most of its supporters, particularly as the lowering of IOP
rarely lasted more than a year. A host of different surgical procedures
were then adopted, discarded or modified. These included iridencleisis,
trephination, cycldialysis, scleral diathermy, etc.
The miotic effect of extracts from the Calabar bean was first
reported by Sir Thomas Richard Fraser (1841-1915) from Edinburgh
in 1862. The isolation of physostigmine and eserine followed and
their effects on IOP studied by Adolf Weber (1829-1915) and Ludwig
Laqueuer (1838-1909). Pilocarpine, the second hypotensive drug
studied, was tolerated far better than eserine. Weber (1877) gave
it a warm recommendation:
`I live in hope (1) that, in some of the chronic and simple glaucomas
pilocarpine will take the place of iridectomy, and (2), that in
many others pilocarpine will serve to make up for the insufficient
effect of the operation`.
Some of the above points still have a modern ring to them, albeit
perhaps relating to other newer drugs (and their marketing strategies).
An important lesson learned from the effect of topical treatments
on the course of the disease was that freedom from subjective
and objective symptoms of glaucomatous attacks that had been observed
during that early period of miotic treatment did not mean that
the disease was necessarily controlled. The development of glaucomatous
cupping occurred in patients in whom regular sustained miotic
administration had suppressed all outward signs of glaucoma.
Just as important was the lesson learned from comparisons of
the two available forms of treatment for glaucoma simplex. A study
conducted at the Wills Eye Hospital in 1895 revealed: ` The effect
of the administrations of eserine and of the performance of iridectomy
in checking the course of the disease is proportionately the same
in the treatment of chronic simple glaucoma`. In absolute terms,
this study showed, probably for the first time, that through conscientious
and systematic use of eserine and pilocarpine the visual status
of the glaucoma patient could be maintained at the initial level
for periods ranging from 5 to 15 years. It soon became generally
accepted that in terms of the evolution of glaucoma, the earlier
treatment was started, the better were the chances of halting
the course of the disease.
Implications for approaches to treatment today:
In 2003, we have a host of new glaucoma diagnostics tests and
instruments, all attempting to detect the disease earlier and
to monitor the progress of the disease more accurately. These
highly sophisticated machines and the technicians required to
work them do not come cheaply in terms of either time or cost
or frustration. In addition, we have a host of new drugs, highly
effective, but not without side effects or indeed, again, cost.
And the patient still has to comply with this treatment for it
to have any effect. Then there are the lasers, which have simplified
surgery, especially iridectomies. Long-term effectiveness of some
of the other forms of laser eg trabeculoplasty, are questionable.
Surgical techniques have been modernized, modified, and individualized,
with improved outcomes, but with more operations being performed
come more potential complications. And has the previous therapy
attempted, such as topical medications, worsened the outcomes?
Although we are now able to detect glaucomatous damage earlier
in the disease process and can institute effective IOP-lowering
therapies, the latter has still remained the mainstay of glaucoma
therapy over the past 150 years. What is important is to emphasize
the importance of early diagnosis followed by early and adequate
treatment. New treatment modalities are also being investigated
such as neuroprotection and improving optic nerve head blood flow.
The genetic aspects of glaucoma is another exciting new field
that may not only aid in treating the disease, but also in prevention.
Finally there is the future possibility that neuroregeneration
may become a viable option.
Conclusion:
It may be easy to glibly suggest that we have not advanced very
much since the middle of the 19th century, but there is no doubt
that our understanding of glaucoma had progressed by leaps and
bounds, and that our modern therapeutic methods are more effective
in lowering IOP, and have less adverse effects than the therapy
of old. We also now have scientific evidence from the randomized
controlled glaucoma clinical trials that our treatment does work
in many cases in controlling or preventing the disease.
In 1924, Duane (in Fuch`s Textbook of Ophthalmology) stated in
relation to Von Graefe`s achievements: `We have only to remember
that formerly every case of glaucoma inevitably led to blindness………..Thousands
there are who formerly would have been forced to sink year by
year irretrievably into the night of blindness, but who are now
saved for vision….`
The glaucoma patient in the 21st century can look forward to
improved diagnosis, effective treatments, and a better quality
of life.
Further Reading:
Duane A. In Fuch`s Textbook of Ophthalmology, ed Duane A, 1924,
JB Lippincott Company, Philadelphia pp 776-808
Von Graefe A. Uber die Wirking der Iridetomie bei Glaucom. Arch
Ophthalmol 1857; 3: 456-555
Weber A. Uber Calabar und seine therapeutische Verwendung. Von
Graefe`s Arch Ophthalmol 1876; 22: 215.
De Wecker L. La cicatrice a fitration. Ann d`occul 1882; 87:
133-143.
Elliot RH, Lagrange PF, Priestley Smith J. Report on glaucoma
operations with special reference to the comparative results attained
by iridectomy and its recent substitutes. London: Trans XVIIth
International Congress of Medicine (section on ophthalmology),
57-146.
Laqueur L. Neue Therapeutische Indikation fur Physostigmine.
Centralbl med Wissensch 1876; 14: 421-422.
MacKenzie W. Practical treatise on diseases of the eye. London.
Longman.1830; 710
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