Fort Lauderdale, Florida, USA, April
30-May 5, 2000
Instead of writing a report, we asked a number of
glaucomatologists to write down their ten most memorable, remarkable or
noteworthy impressions of ARVO 2000. Their contribution is greatly
appreciated. Those who were present at ARVO may try to do
the same - find out how much you remember - and compare. It is
an interesting experience!
It did seem that there was considerable interest in frequency
doubling perimetry, and that many seemed to find it appealing. I
suspect mostly because it is fast and simple, but also the reports are
that it is pretty accurate as well. I personally feel it will still
develop a little more before it is perfected for following patients, but
for detection, many reported favorably.
Progression of field defects is more likely to be deepening
of an existing defect and recruitment of more area into a defect
than development of a defect in a previously normal area.
Variability in a defective region might make it seem so even if it isn't, but
I think the study was done well enough to probably be true.
Genes can be transported for expression in the
trabecular meshwork, opening the potential for treatment of abnormal
meshwork function.
Finally, there were numerous papers that dealt with
various parts of the pathogenic mechanism of glaucomatous damage
to the nerve. In parallel, there was interest in treatments aimed
at various parts of the mechanism(s) in addition to lowering IOP.
Many of the treatments (or maybe all) are, at this time,
hypothetical in the clinical arena, even if some effects can be
demonstrated in the laboratory.
I was interested in the session on the biology of the
choroid with reference to its nutritive functions to the retina. Funny
that the outer retina is so minimally involved in glaucoma.
MMC reaches about 70% of its
scleral concentration at one minute; not much rationale for leaving it on longer.
Prophylactic antibiotics in patients with blebs substantially
increases the risk of late endophthalmitis, and
worsens the prognosis of patients who
received them. (The brighter among us already knew this!)
No imaging technique performs better than careful evaluation
of disc photos to detect early glaucomatous damage.
Induction of endogenous heat shock protein with zinc is
neuroprotective in a rat glaucoma model.
Corneal birefringence artifact is a
huge problem when trying to interpret GDx results.
Genetic contributions to glaucoma are
far more complex than originally thought and, in the end, may be too numerous and
diverse to be of much help, at least for a very long time (pardon
the editorial comment).
GDx and OCT performed similarly in discriminating glaucoma
patients from healthy subjects, but the agreement between the devices was
limited.
New generation OCT may allow
resolution of less than 3 µm in retinal thickness measurements.
Corneal polarization axis is
stable in patients, suggesting that GDx-measured polarization shifts
may provide meaningful information for follow-up.
GDx was better at identifying normals and patients than
patients with localized and mixed visual field defects.
HRT is effective at showing progression of optic disc
changes, often prior to visual field changes.
Anterior scleral canal opening enlarges following acute
pressure elevation in monkeys with experimentally elevated IOP, but not
in normotensive monkeys.
Correcting peripapillary retardation measured with GDx for
macular retardation increases the discriminating power of the GDx.
A motivated observer using
scanning laser polarimetry might correct for corneal dependence either by
measuring cornea, imaging the macula or both (see also Caprioli).
Modern imaging technology has a sensitivity
of 71% and a specificity of 89% to detect
progression, and is better than stereo disc photographs (see also Caprioli).
The sensitivity of scanning laser polarimetry to detect normal
pressure glaucoma (25%) may be lower then for primary
open-angle glaucoma (50%).
An implanted telemetric system for continuous IOP
measurement has been used successfully in monkeys.
Endothelin induced optic nerve ischemia in monkeys caused
topographical optic nerve head changes (HRT) preceding
functional changes (mERG).
Estrogen replacement therapy reduces vascular resistance
in postmenopausal women. Suspension of estrogen
replacement therapy caused a rapid reduction in pulsatile ocular blood flow.
In normal pressure glaucoma after mitomycin trabeculectomy,
the probability of a stable visual field at five years was more than
80% at an IOP of 10 mmHg.
After deroofing of Schlemm's canal, the resistance in the
remaining tissue may not be enough to prevent hypotony.
Pulsatile ocular blood flow increased significantly after Viagra.
Electro-acupuncture reduces IOP and suppresses the
aqueous humor flow rate in rabbits
OCT for filtering blebs: an
advance in relating structure to function, and the potential for sequencing
change in the developing bleb.
Histopathology of visocanalostomy
in monkey eyes: demonstration of the structural changes that occur
with viscocanalostomy (see also Greve).
Objective perimetry in glaucoma:
the use of multifocal ERGs to identify focal change in visual
function.
Correction of the corneal component of retardation with the
GDx: the identification of a correction factor for the corneal
component that alters polarization of light returning from the eye (see
also Caprioli and Greve).
The effect of nonsurgical IOP reduction on the optic nerve
head demonstrated that the Heidelberg SLO is sensitive enough to
measure changes in optic nerve head topography after medical
treatment.
The effect of diclofenac on corticosteroid IOP response in
glaucoma: a nonsteroidal anti-inflammatory agent may suppress
the TIGR protein response in relatives of POAG patients given
topical steroids.
Age-related changes in the ciliary body: the cross-sectional
area diminishes with age accounting, in part, for the shallowing of
the anterior chamber seen with age.
The long-term outcome of glaucoma filtration surgery: 46%
go blind after ten years despite good IOP control, those at risk
have the greater field loss at the time of surgery.
Correlating perimetric sensitivity with structure: differential
light sensitivity is a better correlate to neuroretinal rim area and
ganglion cell loss, than the dB scale.
Caspase-3 is activated in experimental rat glaucoma:
neurotoxic amyloid precursor protein is cleaved by Caspase-3 and the
cleavage products may play a role in ganglion cell apoptosis.
The number of pharmacological agents claimed to be
neuroprotective in retinal or optic nerve injury
continues to climb, now including gabapentin-lactam, TNF, IL-1beta,
unoprostone , serotonin antagonists, and cyclosporin A.
Cell culture and animal model data continues
to accumulate for presumed neuroprotective properties of alpha-2 agonists and
beta-1 antagonists, although more data is needed to show that
topical application of drug results in sufficient retinal concentrations
to match those studied in experimental conditions.
Mechanical pressure on RGC's can increase their susceptibility
to excitotoxicity.
Blocking glutamate re-uptake by Müller cells may mediate
excitotoxic damage to RGC's in pathological conditions.
Adenovirus and adeno-associated virus (AAV) can be used to
deliver genes coding for neurotrophic factors that are neuroprotective .
AAV may be a particularly useful virus for gene transduction,
as it preferentially binds to RGC's.
Retinal ganglion cells of transgenic mice expressing the
caspase inhibitor CrmA in are not protected from developmental RGC
death, unlike the case for the anti-apoptotic gene bcl-2.
Expanding on a previous report, over-expression of bcl-2
in transgenic mice was associated with regeneration of RGC
axons over long distances after optic nerve crush.
Activation of caspase-3 in experimental glaucoma results in
cleavage of amyloid precursor protein, a protein also important in
glaucoma pathogenesis.
Loss of a specific subgroup (koniocellular) of lateral
geniculate nucleus neurons might precede loss of RGC axons in
experimental primate glaucoma.
Frequency doubling perimetry
was found to be an excellent instrument for screening, with good
sensitivity and excellent specificity.
The risk of going blind in very
long-term follow-up of POAG was 17% in a UK study, agreeing with
results from the Mayo Clinic and from New Zealand (see also
Hitchings and the next point).
The risk of an eye progressing to blindness within ten years
after filtering surgery was 46% (mean Ta 14 mmHg) in a Mayo
Clinic study.
Deep sclerectomy did less well than trabeculectomy in
achieving low normal pressures (<17 mmHg in 59% versus 6%, but led
to less lens opacity).
Carassa's randomized trial of viscocanalostomy versus
trabeculectomy continues to show better effectiveness of trabeculectomy.
In a randomized trial of treatments for leaking filtering blebs,
conjunctival advancement outperformed amniotic membrane
transplantation.
Bleb enlargement by needling or revision is a promising
treatment for bleb leaks in a Japanese study (confirming what Al Solish
of LA has been saying).
Cannabinoid receptors were found in ciliary body
non-pigmented epithelial cells and in the trabecular meshwork of human eyes.
Partial optic nerve transection (superior one-third) in monkeys
led to secondary degeneration of 22% of the fibers in the inferior
half of the nerve.
Selective laser trabeculoplasty did as well as argon
laser trabeculoplasty in first treatments, and better in eyes
retreated after ALT.
Forty-six percent of 59 patients
progressed to blindness at ten years after filtration surgery with
ocular pressures of 14.0±4.4 mmHg. Subjects not becoming blind had
ocular pressures of 15.4±3.0 mmHg. Patients becoming blind had more
advanced visual field loss at time of surgery.
In 11.2 years, 45 of 258 (17%)
patients became blind. Field loss in the better eye and mean IOP were related to progression.
Over 45 months, 34 of 218 (15%)
patients progressed. Mean IOP in the progressive group 19.5 mmHg versus 17 mmHg in the
non-progressive group. The progressive group had large
cup-to-disc ratios, a greater number of medications, greater age, and
worse visual acuity.
In 36 POAG patients followed for 16 years, the average rate
of Goldmann visual field decline was 1.4% per year.
In 30 OAG patients followed for seven years, 50% had
significant progression according to linear regression analysis.
