Caroline Richards, editor, Ophthalmology Times Europe®

home

authors

caroline-richards-editor-ophthalmology-times-europe-

This transcript has been lightly edited for clarity.

 Thank you for joining me today, Dr Lubeck, to discuss your presentation on endothelial cells, which I understand you just gave, in fact. It's lovely to meet you here in sunny Milan. I'm Caroline, editor of Ophthalmology Times Europe. Could you please tell me more about your presentation and what the key takeaway points were?

Caroline, we and surgeons who have done MIGs surgery have been drawn more and more to the possible consequences of damaging corneal epithelium as we do our procedures. There's much still to be learned about how these procedures affect the epithelium over the long term.

Canaloplasty, which is procedure I've been doing for about seven years, there was little to no data on its effect on the endothelial. Two years ago, Robert Noecker and I began a prospective study to determine the effects of canaloplasty on the cornea...

We found very, very strongly that canaloplasty has no negative impact on the corneal epithelium compared to cataract surgery alone. So essentially, it has minimal impact to no impact on the health of the cornea.

 Where do you see this research going in the future?

We hope to extend the current study up to 5 years, but we've also embarked on a much bigger data registry project called the iTrack Glaucoma [Global] Data Registry. It's being housed in the ISGR, the National Glaucoma Surgery Registry. And we hope to enrol up to 1,000 patients in that over a fairly short period of time, and then have a much more comprehensive look at knowing the efficacy, safety profiles and the nuanced elements of the procedure.

 It sounds like it will be really valuable data when that comes through.

It's essential. We don't have for this procedure. We don't have a single, large database, and it's been around for a long time.

 Well is anything else you would like to add, anything you're really excited about at present? Or have we covered everything?

The procedure is attractive in the beginning because it's non-destructive, there's no stents left behind. And from a Bayesian standpoint, or reasoning, it makes sense in terms of what it does for glaucoma, and the treatment. It has tremendous implications for the future.

Once we understand not only the biomechanics, but the bio-physiology of glaucoma, I believe that this technology is going to have a future application to different modalities of treatment.

 Oh really? Oh, that sounds excellent. Well, thank you very much for your insights today, Dr Lubeck.

It's a pleasure. Thank you very much, Caroline.

Videos

Dr David Lubeck talks with Caroline Richards of Ophthalmology Times Europe about his ESCRS presentations, touching on surgical effects on corneal epithelium and the iTrack Global Registry for glaucoma.

Investigating the effects of canaloplasty on corneal epithelium

When introducing genetic material into the target cell of a patient to prevent or cure a disease, one approach is to replace an otherwise mutated or missing gene with the correct coding sequence. Another is to inactivate or silence a mutant copy of the gene with a dominant negative or toxic effect (for example, using endonuclease/CRISPR-Cas9, ribozyme or antisense RNA). It is also possible to introduce therapeutically beneficial genetic material such as a ‘killer gene’ into tumours.

These three approaches were introduced by Prof. Isabelle Audo in one of her presentations at this year’s European Society of Retinal Specialists (EURETINA) Meeting on 3rd September in Hamburg, Germany, in the Session on “Inherited Retinal Diseases”. Prof. Audo is based at the Department of Genetics, Institut de la Vision, Paris, France.

However, there is another promising avenue available in gene therapy: optogenetics. In this case, the genetic material consists of light-sensitive proteins which can induce a biological process when exposed to light of a certain wavelength. This has potential in the progressive, inherited disease retinitis pigmentosa (RP), Prof. Audo explained.

The ongoing PIONEER Phase I/II study is a first-in-human dose escalation study that is investigating the optogenetics approach with the AAV2-based candidate GS030 (GenSight Biologics), which is delivered by a single intravitreal injection in the worst-seeing eyes of RP patients.

GS030 encodes the light-sensitive protein red-shifted channelrhodopsin. According to Prof. Audo, the gene is stimulated with an optoelectronic device consisting of a pair of engineered glasses, to transform an external light stimulus into a signal to activate the retinal ganglion cells and the retinal output is sent to the brain for image processing.

The clinical trial is being undertaken at is being at three sites in the United Kingdom (London), Paris (France) and United States (Pittsburg, Pennsylvania) and has enrolled 18 subjects between the ages of 18 and 75 with non-syndromic RP into three cohorts. Patients eligible for the study were affected by end-stage RP with no light perception or light perception levels of visual acuity. An extension cohort expanded the inclusion criteria by recruiting patients with hand motion and counting fingers levels of visual acuity.

The first cohort of patients (n = 3) received a dose of 5.0 x 1010 vector genomes, the second (n = 3) received 1.5 x 1011 vector genomes and the third cohort (n = 3) were administered with a dose of 5.0 x 1011 vector genomes. Dosing in these three cohorts has been completed and, following review by the independent Data Safety Monitoring Review Board, no safety issues were found. Based on this, the Board advised that the highest dose could be selected for the extension cohort, and one patient in this cohort is currently being reviewed in France.

In terms of efficacy data to date, Prof. Audo described by way of a video how a patient with late-stage RP in the second cohort partially recovered her visual function following treatment with a single dose. The patient had been diagnosed with RP 20 years prior to enrolment and, 12 months following injection in her worse-seeing eye, she could correctly locate objects of different sizes and contrasts on a white table in front of her, with a 57% success rate when wearing the light-stimulating goggles, versus 24% without the device.

The optogenetic candidate has been granted orphan drug designation in Europe and the United States.

Another company that is investigating the optogenetic approach in RP patients is Nanoscope Therapeutics. According to Prof. Audo, enrolment is complete in a Phase IIb trial, RESTORE, in 27 adult patients with a diagnosis of advanced RP.

In this trial, the experimental treatment is the ambient-light activatable multi-characteristic opsin MCO-010, delivered in a single intravitreal injection. There are two dose groups that comprise patients over the age of 18-years-old who have a confirmed diagnosis of advanced RP based on clinical examination, dilated fundus examination and genetic testing.

Enrolled patients had a best-corrected visual acuity worse than 1.9 LogMAR (Snellen equivalent of 20/1600), counts fingers/hand motion in the study eye and no better than 1.6 LogMAR (Snellen equivalent 20/800) in the fellow eye during screening. Patients also had the presence of retinal inner nuclear and nerve fibre layers detected on optical coherence tomography testing in the study eye during screening as determined by the investigator and confirmed by the sponsor or designee.

Patients will be assessed over 52 weeks and the primary outcome measures are the efficacy of a single intravitreal injection of vMCO-010 assessed by Y-Mobility test, and the type, severity and incidence of ocular and systemic adverse events, specifically those related to intravitreal injection of the candidate.

Dr Audo concluded by stating that in the future it should be possible to fine-tune the vectors to improve sensitivity and simulation and to target dormant cones to help restore vision.

Articles

Companies are exploring light-sensitive proteins method in patients with advanced disease.

Optogenetics approach could restore visual function in retinitis pigmentosa

It's great to see you. I know you presented yesterday on quality of life—yesterday afternoon. Could you tell me a bit more about the key takeaway points from your presentation?

 Yeah, so I'm a glaucoma specialist, and a cataract surgeon. And nowadays with advances in glaucoma surgery, there's a new type of glaucoma surgery that most ophthalmologists are familiar with called minimally invasive glaucoma surgery. And this is surgery that can be very easily and fits perfectly well when it's combined with cataract surgery.

 So, at the same time, as a patient having a cataract surgery, we can now do operations to better control or optimize their glaucoma.
I've been doing this for at least the last 10 years now. And what I've noticed—certainly in the last few years, as we're doing higher volumes of these patients—is that when patients come back to their post-op visit, the next day or one week later, you can see a big transformation in the patients. They are seeing better, so they're happy. The eye pressures are better controlled, they're taking less glaucoma medications, and they just feel less anxious about glaucoma.

Glaucoma is the leading cause of irreversible sight loss in the world. And a lot of patients worry about this in between the clinic visits, glaucoma can dominate their lives. And you see that once their pressures are better controlled, and you sort of told them their glaucoma is stable, that really allays a lot of their anxiety.

Then you've got the other patients, big group of patients, majority of patients that hate taking their drops. You know, imagine if you have to put drops twice a day for the rest of your life. That can isolate you, can limit your social interactions with others, and again, creates that insular approach that "I have a stigma of a disease or chronic disease."

 And they sort of dissociate themselves from society. So getting patients off glaucoma drops then frees them from that. So they have that sort of physical independence from not being on the drops. But on the other side, their eyes are a lot more comfortable.

Glaucoma drops are effective, or they can make the eyes red, sore, itchy, watery. So we've looked at a study essentially, as opposed to just seeing patients in the clinic, actually doing a study to look at patient-reported outcome measures, using some well-established patient reported outcome measures such as the glaucoma severity scale, glaucoma quality of life, the ocular surface disease index.

So we looked at all the these both before the surgery, four months after the surgery, and just recently 12 months after surgery. And we see a big improvement from before the surgery to four months. And that improvement has been maintained at 12 months.

 So and then when we examine their eyes, we look at the surface of the eyes, look at how healthy their tear film is, how healthy their eyes are in general. And that also has shown a big improvement.

So you know, it's nice to have post-op patients that are happy. They're—happy patients make happy doctors. And really, of course, glaucoma is about controlling the eye pressure, about preventing further visual field loss and keeping patients from visual disability in their lifetime.

But if patients are happier, more confident, less anxious, and have a better quality of life, then that's a that's a huge—

 A win-win. And it's something that probably as clinicians we underestimate, and hopefully these kinds of studies will help make it more commonplace to sort of start off thinking as there's a patient at the end of that eyeball.

 So one step towards that. Lots of more work to do. But yeah, very happy with the initial results.

What would be the next steps for this research?

So the next step would be to apply it to other glaucoma surgeries and not just the minimally invasive glaucoma surgeries but some of the bigger surgeries that we need to do for patients who are a little bit more advanced or the glaucoma is a bit more aggressive, and maybe potentially looking at at other types of surgery as well.

We know some stuff about cataract surgery, but you know, retinal surgery, and those sorts of things, so not just limited to glaucoma. And then within our own data, we've got 12-month data, but it'd be lovely to see whether this is maintained at two years, three years and five years. They're the next steps, really.

Yes. Oh, that sounds really good. Well, thank you very much for sharing your insights with Ophthalmology Times Europe.

Mr Gokulan Ratnarajan recaps his 2022 ESCRS presentation: "A Real World Comparison Of iStent Combined With Phacoemulsification And Endocyclophotocoagulation (Ice2) With Preserflo And Xen-45 Implants In The UK; Short- And Long-Term Outcomes."

Should endocyclophotocoagulation be considered part of MIGS? Mr Ratnarajan delves in

 This transcript has been lightly edited for clarity.

So thank you for joining me, Professor Dirisamer. I understand you participated in an instructional course on refractive surgery. I'm Caroline, editor of Ophthalmology Times Europe, and I would love to hear more about the key takeaways from that instructional course.

Thanks for the kind invitation to talk to you. Yeah, what we tried to say or to transport in this instructional course, are, where are the limitations and indications for the specific treatment options we have in refractive, in modern refractive surgery, either with laser refractive surgery or lens based surgery like phakic IOLs or refractive lens exchange.

Excellent. And what would you say the main challenges are that people have to pay attention to?

Yeah, since we get more and more precise pre-operative assessments, we get nicer and very precise devices based on different technologies like OCT-based, or like, [audio unclear]-based, and also epithelial mapping, for example. So there are many, many parameters for refractive surgeons have to keep in mind and have to look into their decision whether the patient gets refractive surgery and which kind of refractive surgery. This is very important since this kind of an elective procedure. So there's no medical need for that. You have to be more precise, and rule out the suspicious cases. That sounds easy, but it's tricky.

Exactly, there's not really a certain rule. Now you can really say, Okay, this is safe or it's not safe. There are some, but it remains the decision by the surgeon what we do.

And I suppose with more experience, it becomes easier to...

And it's, of course, an individual decision for each surgeon because someone may feel more comfortable with this technology, the other one with the other techniques. So we try to cover the latest publication and latest scientific works and see what changed.

There are some changes. So we are very happy to have epithelial mapping. So this is a tool that it's getting more precise to rule out suspicious corneas.

Yeah, I think we are getting close to zero complication rates.

No, but close enough. I was going to ask you what you're most excited about in the field, but I would imagine it's epithelial mapping. Or is there anything else?

Well, in terms of diagnostic, I think epithelial mapping is pretty, pretty cool. But there was a biomechanical measurements, which are coming more and more in terms of surgical techniques. I think the SMILE technique, which is a femtosecond laser lenticule extraction, I think this becomes the future of cornea and refractive surgery. Yes. Many, many companies are now providing this technique. So let's developing tool we have in our armamentarium.

Yeah, yeah. How long, how long has that been around now? It's just a few years, isn't it?

More than 10 years. Yeah, we probably see next year or so hyperopic treatments for SMILE and cyclotorsion compensation and so on. So this, yeah I'm looking forward to that.

Professor Dirisamer, that was really interesting. Thank you very much for sharing your insight.

Prof. Martin Dirisamer speaks with Editor Caroline Richards about his ESCRS instructional course, "Mastering laser refractive surgery: Indications and outcomes."

Author | Caroline Richards, editor, Ophthalmology Times Europe®

Articles

Optogenetics approach could restore visual function in retinitis pigmentosa

Should endocyclophotocoagulation be considered part of MIGS? Mr Ratnarajan delves in

Investigating better indications and outcomes in laser refractive surgery

Investigating the effects of canaloplasty on corneal epithelium