Top-Six on "From repair to regeneration"

Keith Martin

• The human trabecular meshwork has a remarkable ability to repair itself and regenerate after injury. Modulation of these regenerative responses may help overcome the loss of trabecular meshwork cells and accumulation of extracellular matrix seen in glaucoma.
• In the Moorfields 'More Flow' study of trabeculectomy with 5-flurouracil, not a single subject with a mean eye pressure less than 14 mmHg progressed during the follow-up period, but patients with such low pressures were in the minority. New treatments that modulate the healing response after surgery by manipulating growth factors, extracellular matrix, inflammation and the cell cycle may help many more patients achieve such excellent IOP control after glaucoma surgery, thus reducing the risk of progression.
• Mitochondrial dysfunction occurs during retinal ganglion cell injury and seems to be the point of no return for the functional rescue of affected cells. Long term survival of injured neurons and the initiation of regeneration depends critically on inhibition of mitochondrial dysfunction.
• Stem cell treatments for glaucoma show considerable promise, in particular if Muller progenitor cells isolated from the adult retina are used. However, the problems of rejection and lack of integration and function should not be underestimated.
• Astrocytes in the lamina cribrosa are prominent in the cellular response to optic nerve damage in glaucoma. Although reactive astrocyes in glaucoma have known detrimental effects, they may also exert positive roles such as maintenance of the blood nerve barrier, anti-inflammatory functions and protection of axons.
• One of the the most important barriers to neuronal regeneration in the central nervous system is inhibition by chondroitin sulphate proteoglycan. Chondroitinase, a bacterial enzyme that breaks down such proteoglycans, can dramatically increase the ability of central nervous system neurons to regenerate.

Top-Ten of the Symposium on ocular hypertension

Harry Quigley

In a two-hour symposium dealing with treatment of ocular hypertension, the following were important conclusions:

• Findings of the Ocular Hypertension Treatment Study show that IOP-lowering therapy is beneficial in preventing the development of change in the optic nerve head or initial visual field change.
• Risk factors that make conversion from suspect to definite glaucoma status more likely include higher IOP, larger initial cup/disc ratio, and worse baseline field status.
• The measurement of progressive change in field is complex and the ideal method has not yet been devised.
• Therapy for ocular hypertensives is complicated by inadequate compliance, side-effects, and failure to take effect of quality of life into account.
• Patients and physicians place different values on their vision and on the therapy choices.
• The value that patients place on their vision and on the beneficial and detrimental effects of therapy for glaucoma.
• A cost-benefit analysis suggested that treatment of ocular hypertensives with IOP greater than 24 mmHg is within the cost range of therapies considered valuable in general medical treatment.
• The cost of saving one eye from blindness by the treatment of ocular hypertension was estimated at $ 800,000.
• About 1.3 million ocular hypertensives are being treated in the United States at this time.
• The number of eyes saved from blindness by present therapy of ocular hypertension is only three to five times the number that are estimated to lose reading vision due to complications of cataract surgery that is necessitated by glaucoma treatment.

ARVO Top-Ten

Bal Chauhan

• CAT-152, an anti-TGF-b2 antibody used as a wound healing modulator, was shown not to have a significant advantage over placebo in a multicentre study of patients undergoing first-time trabeculectomy. These results were in contrast to previous positive results.
• Chondroitinase-ABC has been shown to restore neural plasticity by breaking down perineural nets which are thought to limit plasticity in the adult CNS with obvious implications for regenerating RGC axons.
• Statistical image mapping is a novel and exciting technique for detecting optic disc change in glaucoma.
• Outer retinal functional changes with multifocal ERG were shown in experimental monkey glaucoma. Since some of these animals had previously transected nerves ruling out an RGC contribution, these results suggest involvement of the outer retina in this model of glaucoma via a pressure-induced (perhaps ischaemic) mechanism.
• In patients enrolled in the Low Pressure Glaucoma Treatment Study the eye with greater damage was not associated with the eye with the higher IOP. These results are in contrast with previously reported studies that suggested that even in glaucoma patients with lower IOPs, pressure modulated the degree of damage.
• Using the microsphere technique, blood flow in the rat retina was found to be poorly regulated in the face of acute IOP elevation, suggesting that there may be an ischaemic component of damage in rat eyes treated with elevated IOP in rodent models of glaucoma.
• In experimental monkey glaucoma, there was 16-29% axonal loss at the onset of surface height changes measured with scanning laser tomography.
• RGC-targeted gene-knockdown was demonstrated in conditional knockdown mice using an adeno-associated viral vector delivery of Cre recombinase.
• A new valved seton was shown to reduce IOP in rabbit eyes with user defined pressure control.
• Using previously obtained patient, rather than population derived, probability density functions can lead to a 30-60% saving in test time in perimetry without increasing error.

ARVO Top-Ten

Tin Aung

• Functional Ultrahigh Resolution Optical Coherence Tomography provides unprecedented non-invasive imaging of retinal morphology and physiology
• Lower corneal hysteresis and thinner CCT may be independently associated with risk of glaucoma damage.
• The Incidence of Open-angle Glaucoma in a General Elderly Population: The Rotterdam Study gave a five year risk of up to 3.2% in men and 2.3% in women incidence data from a population based study in Europe.
• Polymorphisms in the Interleukin-1 gene (IL-1â +3953T) may protect an individual against developing POAG, results replicated in both American and Indian cohorts.
• Time-course of single cell apoptosis in vivo using video and image analysis of retinal ganglion cell disease model was demonstrated.
• Statistic Image Mapping may be useful in detecting structural change in a series of HRT images.
• Longer-term results of a RCT comparing deep sclerectomy with trabeculectomy found that trabeculectomy offered better IOP control.
• A population-based glaucoma survey in China found that POAG was slightly more common than PACG.
• In a rat experiment it was demonstrated that microtubules make a significant contribution to the RNFL birefringence.
• The latest gene discovered for POAG is WDR36 identified at the GLC1G locus on 5Q22.1.

ARVO Top-Ten

Andreas Boehm

• Neuroprotection means permanent long term cell survival and not only an extension of cell survival for days or weeks.
• Alteration of perineural nets restores plasticity of the central nervous system and enables to modulate cns functions.
• Decreased blood pressure increased the likelihood of glaucomatous neurodegeneration in DBA/2J mice.
• Crushed axons regenerated into the optic nerve head in the presence of a macrophage activator or elevated intracellular cAMP levels in adult cats.
• Dendritic pathology of lateral geniculate neurons in the brain occurs even if no significant optic nerve fiber damage is detectable.
• Memantine protects lateral geniculate nucleus neurons from shrinkage following glaucomatous optic nerve injury.
• Increased peptidylarginine deiminase type II activity is associated with glaucomatous optic nerve damage.
• High-speed ultrahigh resolution OCT allows images of the living retina with a resolution less than 5 µm.
• Scleral biomechanical properties are a major determinant of optic nerve head biomechanics.
• Corneal thickness and corneal hysteresis are independently associated with glaucomatous damage.

Issue 7-1

Table of Contents Editor's Selection

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