Insight - August 2019

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Professor JONATHAN CROWSTON, professor of

ophthalmology at Duke-NUS Medical School Singapore

and former CERA director, tackled the subject of

Primary open-angle glaucoma disease progression, an

art with notoriously poor accuracy.

GLAUCOMA PROGRESSION

Overall, 75% of cases progress and the remaining 25% do not progress.

Furthermore, it takes a long time to study progress validly, meaning

few undertake the task due to it being impractical. He also noted that

neuroprotective trials were prohibitively expensive and were unlikely to be

undertaken either lightly or without significant support.

Stressed RGCs can lead to cell death and annexin V (also known

as annexin A5, a cellular protein) assays permit quantification of the

number of dying cells. However, that in turn only allows a rough estimate

of the number of residual RGCs. Cells that have already undergone

phagocytosis fluoresce.

It is estimated that about 65 RGCs die each day as part of the normal

ageing process. Also of interest are RGCs undergoing dendritic pruning

involving axonal cytoplasmic and mitochondrial micro-changes.

Recovery of RGC function remains largely unknown and its exact nature

is still debated.

RGC recovery in rodents has been confirmed in the lab over a period of

at least 7 days. Importantly, real-time assessment of RGC health in a lab

setting is now possible.

THE BIG PICTURE

Ophthalmologist, Assistant Professor LUCY SHEN,

a glaucoma specialist at Massachusetts Eye and

Ear Hospital, gave a brief presentation on imaging,

particularly wide-field imaging.

Swept-source optical coherence tomography (OCT)

already offers 12 x 9 mm image areas, allowing for a

useful analysis of the retinal nerve fibre layer (RNFL).

Adaptive optics imaging offers a view of individual

cells and nerve fibres, but the process is slow and

intense.

Other ocular parameters of interest include Bruch’s

membrane opening, minimum rim width, and lamina cribrosa depth,

including its deeper layers between 40 and 80 microns further out.

A recurring difficulty involves marrying old and new data due to different

instruments and techniques creating incompatibilities. Parameters of

interest include changes in RNFL thickness and macula ganglion cell

populations, among others.

Another clinical pursuit is reconciling structure and function. OCT-A, for

example, uses high-speed OCT to detect retinal features that change

over time, especially moving blood. In NAION (Non-arteritic, Anterior

Ischaemic Optic Neuropathy), the density of the superficial retinal blood

vessels is reduced. Shen predicted that future OCT devices would be

better at characterising the glaucoma patient and their eyes. However,

she also noted that artefacts, including optical artefacts, remain an

imaging issue.

WHAT’S BEYOND MIGS?

Well-known Canadian eye surgeon and

ophthalmology academic Professor IKE AHMED

spoke about minimally invasive glaucoma surgery

(MIGS) and other anterior chamber drainage

approaches to glaucoma therapy.

Significant factors to be considered when selecting a treatment

regimen include quality-of-life, cost, and the approach’s ability to

prevent blindness. According to Ahmed, the invasiveness of the ab

interno MIGS approach “does not matter”, noting that only part of the

trabecular meshwork is involved in filtering at any one time.

Despite the number already available, he believes that more

devices are still required and that there are some novel examples

in the pipeline. He also holds the view that the interest in MIGS is

considerable, based on the recent number of publications that focus

on the devices. Promoting further interest is the fact that there is a

plateau across the purely surgical approaches to glaucoma.

One new approach is the Swiss eyeWatch; an adjustable-flow

device featuring a magnetically-coupled, external, adjustable valve.

The eyePlate drainage shunt is inserted sub-conjunctivally and is

connected to the eyeWatch via a short elastomeric tube. A rigid

extension of the eyeWatch component is plumbed into the anterior

chamber. Sutured scleral tissue is used to protect the ‘system’ once

implanted.

When placed directly over the implant, the eyeWatch Pen surgeon’s

tool indicates the current valve setting. It also contains a magnet that

is used to adjust the eccentric-cam clamp that impinges upon the

eyeWatch’s internal tubing, altering outflow control.

Other devices take a suprachoroidal approach, but he cautioned

that any such device needed to be anti-fibrotic to avoid problems in

the longer-term. Another device is the Camras Shunt from Camras

Vision, now marketed as the Sollevio from Alievio Inc. The shunt

targets lower levels of intraocular pressure (IOP), less than 14 mm,

and incorporates a micropore antibacterial filter to prevent ingression

of micro-organisms into the anterior chamber. Its outlet is located

externally, under the upper eyelid.

The iDose (Glaukos) is an intraocular implant that delivers travoprost

after a ‘micro-invasive’ surgical procedure. More than half the

participants in an early trial showed about a 30% IOP reduction at 12

months compared to baseline results. A much larger clinical trial is

underway.

The XEN Gel Stent (Allergan) is a permanent, porcine-gelatine/crosslinked

with glutaraldehyde, anterior chamber implant that shunts the

anterior chamber to the sub-conjunctival space. A needle ‘introducer’

is used to enter the anterior chamber. It is already available.

In a later presentation, Professor Andrew White from Westmead

Hospital (Sydney) reported on his department’s experience with the

XEN shunt combined with MMC (mitomycin C used in a large volume/

low concentration dose). They found a rapid rehabilitation, with

visual acuity back to baselines within seven days. Insertion required

minimum manipulation, but care was required to avoid excessive

pushing at the time of insertion. As with all tubes, there is a risk of

erosion at the insertion site. His study used topical steroids for 4-6

weeks post-insertion to prevent local fibrosis.

Ahmed wrapped up his presentation with a prediction that in the

future, microstenting of filtering blebs would be used as a possible

glaucoma therapy, or as an adjunct to existing therapy.

INSIGHT August 2019 47

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