The Goal is Improvement: Saludogenesis
Mark R. Lesk, M.Sc., M.D., FRCS(C)
Department of Ophthalmology
University of Montreal
Montreal, Quebec, Canada
Spaeth Fellow, 1994-95
Saludogenesis means a return to health and this is the goal in
glaucoma therapy: to move towards a more normal physiologic state.
Dr. Spaeth proposed almost two decades ago that reversal of cupping,
when present following sustained therapeutic reduction of intraocular
pressure, might indicate an adequate decompression of the optic
nerve head and might predict future stability of glaucoma (1).
During my fellowship year we began to study this
phenomenon in detail using the Heidelberg Retina Tomograph in
a cohort of patients scheduled for glaucoma surgery. Following
on the work of L.J.Katz (2) and G.L.Spaeth and others, but using
much more sensitive technology, we were able to show that improvement
of optic nerve head morphology or ‘reversal of cupping’
was present in most (but not all) eyes undergoing at least a 35
% reduction in IOP (3).
We continued these studies in Montreal where
we have recently shown that ocular hypertensives undergoing sustained
IOP reduction have the same degree of reversal of cupping as glaucoma
patients (4). This unexpected finding runs counter to literature
that suggests that the optic nerve head, or, more specifically,
the lamina cribrosa, has reduced compliance in glaucoma. Could
it be that our ocular hypertensives have already developed some
rigidity of their optic nerve head structure? Regardless, they
too show improvements in optic nerve head morphology following
sustained pressure-lowering therapy.
We observed larger changes in optic nerve head
morphology in both glaucoma patients and ocular hypertensives
that have thinner corneas (4). Changes in the Heidelberg parameter
‘mean cup depth’, which reflects movements of the
lamina cribrosa, was best correlated with central corneal thickness.
We know that in the recent Ocular Hypertension Treatment Study,
thinner corneas were a major risk factor for the development of
glaucoma (5). Only one-quarter of this risk could be explained
by the artifact a thin cornea induces in Goldmann tonometry. It
appears from our data that a thin cornea might be connected to
a thin sclera and to a thin lamina cribrosa which is more compliant.
Increased lamina cribrosa compliance would then be a risk factor
for progressive ocular hypertension and glaucoma, possibly by
not properly supporting axons, glia and blood vessels that pass
there. This finding points to the importance that decompressing
the optic nerve head is likely to have in the stabilization of
glaucoma.
We have examined how optic nerve blood flow changes
as IOP is reduced. Vascular changes are likely to be an important
part of saludogenesis. In glaucoma patients undergoing sustained
therapeutic IOP reduction, we found a major increase in blood
flow in the neuroretinal rim of the optic nerve head (6). This
improvement is not seen in most ocular hypertensives, whose blood
flow is close to normal at baseline, and who appear to autoregulate
their blood flow (with certain exceptions discussed below). The
improvements in rim blood flow in the glaucoma group indicate
that they do not autoregulate their blood flow. They also demonstrate
one of the major consequences of IOP reduction in glaucoma: it
improves blood flow in the neuroretinal rim of the optic nerve.
We do not know if this improvement in blood flow is necessary
for the patient to benefit from the IOP reduction. Prospective
trials will be required to investigate this.
Patients showing the largest increases in rim
blood flow following IOP reduction were more vasospastic than
the others, suggesting that vasospasm may underlie the vascular
deficiency at baseline (7). This finding applied even to the ocular
hypertensives. Are these vasospastic ocular hypertensives at greater
risk of developing glaucoma? Their optic nerve vascular autoregulation
appears already to be partly compromised.
Even at baseline, significantly lower neuroretinal
rim blood flow was measured in ocular hypertensives with larger
cup/disc ratios (>0.4) than in those with smaller cups (8),
suggesting that a defect in blood flow is present very early in
the disease, even prior to the development of visual field defects.
Saludogenesis may refer to return to health of
morphology, blood flow, levels of circulating factors, local proteins
or enzymes, expression of genes or many other things in the eye
or body. The goal is to bring the eye and the patient back to
a state of health in which glaucoma will stop progressing. We
are starting to understand how to achieve this.
References
1. Spaeth GL, Fellman RL, Starita RL, et al. Anew management
system for glaucoma based on improvement of the appearance of
the optic disc or visual field. Trans. Am. Ophthalmol. Soc. 83:
268-84, 1985
2. Katz LJ, Spaeth GL, Cantor LB, et al. Reversible optic disc
cupping and visual field improvement in adults with glaucoma.
Am. J. Ophthalmol. 107: 485-92, 1989
3. Lesk MR, Spaeth GL, Azuara-Blanco A, Araujo SV, Katz LJ. Reversal
of Optic Disc Cupping after Glaucoma Surgery, Analysed with a
Scanning Laser Tomograph. Ophthalmology 106(5): 1013-1018, 1999
4. Hafez AS, Bizzarro RLG, Lesk MR, Changes in optic nerve head
topography following therapeutic intraocular pressure reduction
in glaucoma patients and ocular hypertensives. Manuscript in preparation
5. Gordon, MO, Beiser JA, Brandt JD et al. The ocular hypertension
treatment study: Baseline factors that predict the onset of primary
open angle glaucoma. Arch. Ophthalmol. 120:714-20, 2002
6. Hafez A, Bizzarro RLG, Rivard M, Lesk MR. Changes in optic
nerve head blood flow after therapeutic intraocular pressure reduction
in glaucoma patients and ocular hypertensives. Ophthalmology 110(1):201-10,
2003
7. Hafez AS, Lesk MR., Correlation between finger blood flow
and changes in Optic Nerve blood flow following therapeutic intraocular
pressure reduction in glaucoma patients and ocular hypertensives.
Submitted, J. Glaucoma (2003).
8. Hafez AS, Lesk MR. Optic nerve head blood flow in glaucoma
patients, ocular Hypertensives and normal subjects measured by
scanning laser Doppler flowmetry. Am. J. Ophthalmol (in press)
2003
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