Highlights of the ARVO Meeting
April 30-May 4, 2006, Fort Lauderdale, Florida, USA
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Glaucoma New Ideas session
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Claude Burgoyne
- Spada et al. described the first use of metabolic mapping
to clinically measure retinal mitochondrial function in monkeys
which were either bilaterally normal or had been given severe
experimental glaucoma in one eye. While inter-eye differences were
minimal in the bilaterally normal monkeys, profound differences were
detected in the experimental glaucoma eyes which suggests that
changes in the metabolism of RGCs and their axons may be clinically
detectable prior to RGC apoptosis.
- Chen et al. presented the first simultaneous, ultra-high
speed, ultra high resolution spectral domain OCT images of the
optic nerve head and retina of human patients with early to severe
glaucoma, suggesting clinical OCT imaging with greater speed and higher
resolution is in development.
- Poeschla et al. reported the first injection of eFGP
fluorescence encoding, FIV-based lentiviral vectors into the anterior
chambers of four monkeys with good (up to nine months) long-term
eGFP expression, without evidence for IOP elevation or active
inflammation - moving glaucoma gene therapy closer to clinical reality.
- Dahlman et al. described a novel system for
simultaneously imaging and micro-culture force manipulating ocular
fibroblasts so as to monitor and manipulate the mechanisms of
matrix contraction and one day influence ocular healing. This
experimental system may allow the controlled study of pharmacologic
manipulations of glaucoma filtration surgery.
- Cordeiro et al. reported the expression of Beta Amyloid
in hypertensive rat retinas, as well as apoptotic death of retinal
ganglion cells following Beta Amyloid injection into the vitreous
in a separate group of eyes. Their studies suggest a role for Beta
Amyloid in glaucomatous damage to the rat retinal ganglion cell.
- Di Polo et al. evaluated the neuroprotective effects of
intraperitoneal Galantamine (currently approved as an oral agent
for Alzheimer's Disease) in the rat experimental glaucoma model and
found protection of both RGC stroma and RGC axons (counted in the optic
nerve) at five weeks. While preservation of visual function remains to
be determined, this is the first demonstration of Galantamine
neuroprotection in glaucoma.
- Schmidt et al. measured antioxidative activity in serum
and aqueous samples of 50 POAG and 50 normal control patients
undergoing cataract surgery and found no changes in serum levels, but
aqueous anti-oxidative activity to be increased in early phase POAG and
unchanged in late phase POAG patients compared to control. Their work
suggests that treatment of POAG patients with anterior chamber
anti-oxidants, particularly late in the disease, may be important.
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ARVO Top-Ten
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Mingguang He
- Based on the five-year and ten-year incidence data of open-angle
glaucoma in a cohort from Blue Mountain Eye Study, the
incidence was found as 4.5% (95%CI: 3.5~5.5), higher in female (5.6%)
than male (3.0%), increasing markedly with age. Higher IOP, cup
disc ratio > 0.5, disc hemorrhage and reduced corneal thickness were all
associated with increasing risk of glaucoma.
- IOP was stable up to six years among untreated patients in EMGT
trials. Only exfoliation was associated with more elevation of IOP.
About 67.8% of control patients progressed in six years. Progression was
associated with exfoliation, higher IOP, having both eye eligible, older
age and worse baseline MD.
- After integrating a novel spatial filter to the traditional visual
field progression based on point-wise linear regression (PROGRESSOR for
windows software), the specificity improved from 85.7-95.4% to 96.8-100%
in the identification of subjects without progression. About one
third of those identified as progression by either filtered or
unfiltered VF also demonstrated progression by HRT.
- The More Flow Surgery Study in Moorfields demonstrated that both
degree of reduction and variability of IOP were important in the
progression of structural optic nerve head damage identified by HRT
after trabeculectomy.
- A prototype system spectral domain OCT obtained images at a speed of
73 times faster than commercially available OCT system. The prototype
requires less optical power into the eye and allows a high-resolution
delineation of the optic nerve head.
- By a comparison of three normal and three POAG human donors,
extracellular matrix (ECM)/fibroticgene expression in lamina cribrosa
cells was found to be markedly different. Hypoxia, mechanical sketch and
TGF-b1 induced glaucomatous gene clusters in
normal lamina cribrosa cells.
- Using immunized Lewis rats, the study suggests that RGC death in
selected glaucoma patients likely involves failure of immunoregulation
of the microglia/T-cell/RGC axis. This is perhaps through the
pro-apoptosis and protective pathways.
- Using a simultaneous imaging and micro-culture force monitor system,
ocular fibroblasts are involved in the scarring of the eye. The system
is promising for quantitative assessment of matrix contraction and
perhaps the contraction-modulating effect of new drugs in the future.
- An international collaborative project suggests differences between
ethnic groups in HRT parameters, both in the absolute values and
correlation with disc size and age. This finding underscores the needs
for generating ethnic-specific databases.
- By examining 484 population-based subjects (after excluding those
with established occludable angle at baseline), a study demonstrated
20.2% of subjects with an ACD < 2.53 mm will develop occludable angles
over six years.
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ARVO Top-Ten
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Keith Martin
- Combining 5-FU with hyaluronic acid markedly prolongs drug release
from tissue and has the potential to improve the treatment of bleb
failure.
- In rat and mouse models of glaucoma, IOP measurements using
the TonoLab tonometer match manometric IOP more closely than TonoPen
measurements. The TonoLab also requires fewer applications to acquire
readings and reduces IOP less when multiple measurements are taken.
- Rat retinal microglia increase in number and reactivity in response
to IOP elevation and respond differently to duration and fluctuations in
IOP.
- In Singapore patients with unilateral acute primary angle closure,
the risk of developing glaucoma in the fellow eye was 5.1% at a mean
follow up of six years.
- Retinal ganglion cell loss in the DBA/2J model of glaucoma is
sectoral with a pattern that suggests damage to optic nerve bundles at
the optic nerve head.
- Reductions in the size and complexity of dendritic trees of rat
retinal ganglion cells were observed following induction of ocular
hypertension with mean, peak and fluctuation in IOP influencing the
degree of dendritic pruning.
- Encapsulated cell technology (ECT) is a promising method for
long-term drug delivery to the posterior segment of the eye.
- Selective inhibition of c-Jun N-terminal kinase (JNK) is strongly
neuroproctective in cultured retinal ganglion cells exposed to either
excitotoxic injury or neurotrophin withdrawal.
- Annexin V labelling, combined with scanning laser ophthalmoscopy
allows in vivo imaging of apoptosis in the mouse eye.
- Secondary degeneration in the optic nerve appears to involve
activation of the MAP kinase and p53 signal transduction cascades, as
also occurs in glaucoma and after complete optic nerve transection.
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