Eye health #3

00:00:03: Welcome to Crystal Clear.

00:00:05: In this podcast, we share knowledge and experiences around cystinosis To help make living with this chronic disease a little more manageable And a bit easier in everyday life.

00:00:16: We're glad you are here With us!

00:00:28: Our guests are Ophthalmologist Rachel Bishop from the United States and pediatric ophthalmologists Sismito Biswas, from The United Kingdom.

00:00:37: Great to have you with us!

00:00:39: And a warm welcome.

00:00:57: But my involvement with cystinosis dates to fourteen years when I was working at the National Institutes of Health NIH here in Bethesda, Maryland treating patients who were on our Cystinosis research protocols.

00:01:10: We had a couple hundred patients involved in this research and i developed a keen interest.

00:01:20: So I'm just delighted to be able to speak to an audience of patients and families who have cystinosis.

00:01:27: Thank you for having me!

00:01:49: children with cystinosis and adults in our hospital as part of a multidisciplinary team.

00:02:00: We're one of three centres in England, In the UK that are specially funded to see their children and adults with this rare disease And we've been doing it for several years.

00:02:18: first started cystinosis when I was an early consultant in pediatric ophthalmology, and we were seeing many of these patients in our clinic but not part of a MDT.

00:02:34: And i sort of realized that these patients are already being managed in somewhat variable manner... ...and as a result after attending a national meeting.

00:02:48: So I think Rachel was there, and suddenly realized that patients were being managed in much more coordinated and multidisciplinary way.

00:03:00: so we brought back to Manchester now but it's been extended into our National Service.

00:03:06: so i'm delighted be here and share my experience with everyone

00:03:13: And maybe, Suspita I might add on that note.

00:03:16: We were you and i were lucky to be involved also with Claudia Prickinger in the development of the guidelines for treatment of eye disease That was Published In Germany To apply to Europe and Of course extending beyond for care For patients with cystinosis and it Was a pleasure working together On that.

00:03:37: so yes our paths have woven together over the years, and as everybody listening knows this is an orphan disease.

00:03:44: This is a rare disease And it has a tight community of families and patients involved.

00:03:49: so one of the reasons we remain involved Is that?

00:03:53: um...this is really A very close-knit Community and I'm grateful to be part Of It.

00:03:59: i may ask you The first question says me dough That people are interested in.

00:04:03: We certainly hear this at the family meetings which At what age should eyedrops be started in a patient with cystinosis?

00:04:11: Yeah, thanks.

00:04:12: So this is... there's some element of uncertainty as to the exact age at which you know eye drops should be prescribed but we do know that with the infantile cystinosus condition it's present from very early on and crystals are probably forming within the cornea, within the first few months of life.

00:04:45: They can be quite hard to see.

00:04:46: that's the difficulty I think in infancy unless you really know what your looking for.

00:04:54: And from that point of view examining the eyes with a slit lamp either table mounted or handheld can be very helpful.

00:05:05: And knowing where to find the crystals in the early stages is also important because they're located in the peripheral cornea, peripheral anterior cornea and it could be quite fine deposits.

00:05:20: so I think definitely as soon you start to see crystals eye drops should be started can be as early as five, six months of age.

00:05:38: However I am aware that you know patients maybe just starting their treatment journey in cystinosis and they're on an awful lot of medications including renal replacement therapies for parents to kind of take on board the additional eye drop treatment.

00:06:09: So I think we had a discussion, didn't we?

00:06:14: When they were making these guidelines about when to start these eye drops and I think our view was that as soon as possible but as soon the treatments that they needed to get started systemically in child.

00:06:36: And, I think there isn't a lower age cut-off as far as i'm aware with all of these eye drops prescribed so you can prescribe them as soon as your parents are able.

00:06:56: Yeah,

00:06:59: well I completely agree and i think.

00:07:04: I appreciate that it is not an emergency And as you so well stated parents and families are under a lot of stress in many demands In just learning how to begin the treatment at so many levels?

00:07:23: a clinic and drops are started at a few years of age.

00:07:31: We used to not even start before age, you know five six.

00:07:35: typically these patients still do very well in they can clear the crystals.

00:07:40: but like you said I believe patients do best when we don't let the crystals accumulate or the smallest accumulation possible.

00:07:49: so that's kind of the idea between starters early as possible.

00:07:53: But please don't feel that if you weren't able to start in your child's first year of life, but you have damaged your child.

00:08:00: That is not true and it's not a helpful guilt to carry.

00:08:05: so I agree fully.

00:08:07: You start when you have the capacity to handle this added burden.

00:08:10: The other benefit just starting early is as we all know, we are creatures of habit.

00:08:16: We learn things.

00:08:17: so even if you start with one drop a day that child is beginning to get used to receiving a drop.

00:08:23: So one drop per day and maybe once they're comfortable with that You increase two drops a day And such like this.

00:08:30: This works very well.

00:08:31: It's easier for all involved The parents then the children.

00:08:37: So happily unlike systemic therapy which is essential right when diagnosed.

00:08:44: The eye drop therapy can lag behind a little bit and patients still do very well?

00:08:52: Yeah, thanks, Sergei.

00:08:52: I mean i think the important thing is to get into kind of routine with this because we know that the oral medications it's important to get timing right for that.

00:09:10: so routine has kinda built in optimal management of patients with cystinosis.

00:09:17: So it would be helpful as well to have routine built in, uh...as far the eye drops are concerned but It's a question how they've build that into the day.

00:09:29: But I think we'll cover that later on this podcast.

00:09:34: Um so i'm gonna ask you a question Rachel about who should prescribe these?

00:09:44: Do you think it should be the role in responsibility of the ophthalmologist or the nephrologist?

00:09:49: What do you think, Rachel.

00:09:52: Well my view on this is that ideal person to prescribing medicine is a doctor who is performing an exam.

00:10:01: so if I drop, it's the opthamologist in the ideal use of the drops.

00:10:10: I do like that.

00:10:10: our guidelines and are thinking is rooted in reality, and the reality as many patients will be seeing or they certainly we'll see nephrologist before the ophthalmologist.

00:10:20: And so if a nephrologist is comfortable prescribing the drops getting patient started then that makes their way to the opthalmologist after some amount time.

00:10:33: That's also very fine.

00:10:35: And the reality is that many of our patients are prescribed drops first by the nephrologist and then, you know make their way into the care of ophthalmology.

00:10:44: There's nothing wrong with that as we'll discuss when we talk about timing of eye exams The important point is that those patients do get in to the Ophthalmologist chair so that the eyes can be assessed and proper guidance can given.

00:10:58: Thanks yeah I fully agree everything you've said there, Rachel.

00:11:02: I think that we have experience of our nephrologists prescribing sustainably in eye drops and the important thing is when they are prescribing their happy about dosage or advising likely to experience through routine use of these eye drops.

00:11:31: I'm also happy about telling them how to administer the eyedrops etc, so this is obviously something that can develop as a skill within.

00:11:47: you know the nephrologist Particularly when they interact with each other and you know, if the nephrologists are able to communicate effectively.

00:11:58: Build each others knowledge base about respective treatments for this young person or child then it builds that confidence in flexible approach to prescribing.

00:12:14: so I think thats key really is.

00:12:17: there's good communication I think between nephrologists and ophthalmologists to enhance that prescribing capability.

00:12:26: Actually, what you've said points something in this prescribing pattern.

00:12:35: when it's a multidisciplinary team those nephrologists are quite familiar with the experience of the family giving eye drops or patients themselves getting eyedrops.

00:12:47: The reason we both, it sounds like prefer that the ophthalmologist be as involved as possible early on is there are subtleties which will speak about to administering the drops.

00:12:58: So clearly you say its a skill and skills are best acquired when taught they're right technique early.

00:13:04: so one of reasons why this really quite ideal for the opthalmologists to prescribe the drop is take time can teach properly how put them in all these details you've just mentioned.

00:13:16: So yeah, if your nephrologist is... If we're all at these meetings together then this is not new news to them?

00:13:25: If they are a little less familiar or operating outside of a multidisciplinary team than it would fall more heavily on the ophthalmologist to do that education.

00:13:34: so I might ask you... Sorry!

00:13:37: I'm gonna ask you Sosmeto in terms of practical tips.

00:13:42: a child diagnosed with cystinosis.

00:13:48: I was given the drops, my child doesn't like receiving them.

00:13:52: she squeezes her eyes closed tight.

00:13:54: what can you tell me to help me with this situation?

00:13:59: Yeah i mean it's fair to say no young child or infant particularly enjoys having eye drops put in.

00:14:06: and um...I think that uh..what I often tell parents do To a certain extent depends on the formulation.

00:14:15: We will discuss the formulations, I think in short while.

00:14:19: but so In The US i Think you use sister around don't You?

00:14:25: and That's quite an aqueous Formulation.

00:14:29: So it was a watery eyedrop.

00:14:30: that's

00:14:31: right.

00:14:32: in many parts of Europe And in UK we Use A more viscous Formulation Which is called Sister Drops.

00:14:42: now If you're using an aqueous eye drop, I tend to advise parents not worry too much about the eyes being closed because it is a natural response for a child close their eyes when they are having something put in them.

00:15:01: And rather than fight and make big struggle with the child... It's probably best allow them to lie back maybe on a couch or bed, and then place the drop in the inner corner just where the nose and the eyelids meet.

00:15:22: That's called medial canthus.

00:15:24: Place of dropping the medial canvas.

00:15:27: And we know from lots studies that actually if you do this and allow your child to gently blink Or physically pull it down eyelid down a little bit, drops get in.

00:15:45: So we know that drops will get in and also it will sting.

00:15:51: so what I tell parents to just be aware of is the drops will sting when they first start but you know its a sign that it's getting there.

00:16:06: because obviously if then you wonder whether actually the drop has got in.

00:16:14: The eye will only take a certain volume of eyedrop, so if they make a bit of a mess... ...of the first drop going in don't be afraid to put a second drop-in If you feel that it's not properly got in the eye.

00:16:26: You won't overdose from having, y'know A couple drops put into your eyes or even three if you feel like you've missed the second time round.

00:16:37: and afterwards, you know lots of praise Lots of rewards star charts Something that will make the child feel but it's been worth it because at the end of a week Of having these eye drops in It's going to be an ongoing challenge.

00:16:59: But if they feel good about it all and I think They've achieved something then that makes The whole thing easier In the long run.

00:17:09: Rachel, what do you do?

00:17:11: Yeah.

00:17:12: So I love that technique and then as the patient gets older, an age as the individual can do.

00:17:29: Very often, certainly an eight-year old uh can be putting in their drops.

00:17:33: very often um but of course it depends on the maturity of the child.

00:17:38: and then teaching the good technique for that I'm excited.

00:17:42: i think there are some excellent videos on how to self administer drops and I believe one is even being put in production, uh...in German.

00:17:51: Um that i think will be released shortly with our guidance on that.

00:17:55: um.

00:17:56: And so if say the child is at this point ready to self-administer?

00:18:01: I think teaching that technique One way that it's helpful Uh for a slightly older child we're speaking now Is they wash their hands They open the whichever The bottle the vial whatever the cases of what they are using on their cheek, and then that is the scaffolding on which the other hand—that's the dominant hand.

00:18:22: The hand holding a bottle can rest.

00:18:25: if they're lying back with their chin up because you are sitting in your chair or laying down in bed by putting one hand as the scaffoldings The arm is not moving, so it's stable and they can develop a pattern for how to put the drop in.

00:18:47: They pull down a little bit on the hand that is on the cheek So the lower lid has pulled down a Little bit and the drop can be placed into the lower lip.

00:18:55: It doesn't have to land smack dab In the middle of the cornea-the clear part of the eye which Is more irritating?

00:19:02: I take time To teach this in the exam room And then they go home and practice.

00:19:06: like you said, a drop missed here or there is no problem.

00:19:09: There's no

00:19:09: overdosing.".

00:19:11: The only other thing I'd say about eyedrop administration in terms of timing—and the routine that you spoke about was so important—we have learned even though for example sister and drops are approved by FDA in the United States to be administered every single hour while awake because this study.

00:19:33: The good news is that's actually not the frequency required for successful treatment in patients.

00:19:39: In fact, we know from years of experience drops getting into the eye six to ten times a day for these liquid cistern drops.

00:19:57: So those can be spaced rather than every hour, and those can space in groupings that are closer to an hour so long as the eye doesn't react by feeling irritated from those compounds.

00:20:12: two, three drops then they might get the remaining four to six drops in after school.

00:20:17: You know half hour apart something like this and it alleviates the burden of feeling that they have to do this every single hour or miss out on fun events.

00:20:31: And the real test is just when the child comes back for the eye exam, if the eyes are well controlled and the accumulation of crystals is really minimal.

00:20:41: Minimal or none but basically minimal then it's working.

00:20:44: they're doing great.

00:20:45: so I try to recommend a routine that fits with their individual schedule and this much easier for families and kids.

00:20:54: Yeah i think thats'a really important point you've made there Rachel in terms adjusting the frequency according to time of day and when it's convenient be able to put drops in.

00:21:10: Because we know its contact time, isn't there?

00:21:13: It is probably a contact-time of eye drop with ocular surface that really determines how effectively clears crystal from cornea.

00:21:25: so...it doesn't matter if that contact time is maximized in the morning or middle of a day, as long you're taught up the total time and it's roughly the same on daily basis.

00:21:39: So I think contact-time is an important thing to have a concept off if your able put into drops more frequently because its convenient than yes so be it that would best do.

00:21:58: In addition to this obviously as I said in Europe Many countries in Europe are using the viscous formulation.

00:22:06: So, This is a sister drop formulation.

00:22:08: so it's a little bit different with their sister drops.

00:22:12: What i know from?

00:22:14: The use of the sister drops Is that be the bottle design Has the squeezer in the tip not the actual bottle itself which has a glass file and has to be squeezed between finger and thumb.

00:22:30: Your technique that you describe is excellent using one hand as support for the other hand, again The sister drops because it's quite thick.

00:22:41: It takes quite a while And this is the thing patients often say When they're putting their sister drops in.

00:22:48: They are squeezing This drop takes long time To come out of the bottle.

00:22:53: That creates anxiety.

00:22:56: you know again they're sort of shutting their eyes and closing the rise, it can be a bit messy.

00:23:02: And I think your... Again the concept of putting a drop in the corner of the eye works.

00:23:10: still we know that the sister-drop formulation when gets to body temperature becomes less viscous.

00:23:22: but You know, when you're squeezing out the bottle it is quite thick.

00:23:29: Sometimes I say to people balancing the bottle or tip across the bridge of their nose so its lying horizontally can be helpful...across the bridge at the nose.

00:23:40: So that's another similar way of stabilizing it.

00:23:44: Of course depends on your nose!

00:23:47: Some have a bigger nose than others Again, because it's quite thick.

00:23:57: It can get entangled with the eyelashes and I know that a lot of people do complain about the eyelashes getting a bit sticky And stuck together.

00:24:08: so i think as soon As you feel is gone in The eye You Can wipe the eyelashes Because it will leave A residue otherwise Which can be a bit troublesome.

00:24:20: So those are just some additional things to think about.

00:24:23: I had one parent, which is very interesting—one parent who was using the sister drops and they said that they used to keep it in their top pocket before they put the drops in the eye —and that would warm up a little bit more than just you know when they took its straight from the

00:24:40: packet.".

00:24:41: And that allowed it to be a little but more runny and was able to apply the drops a bit more effectively that way.

00:24:48: so that's another potential hint Although, you know I did ask the company at the time.

00:24:55: You know will raising the temperature of a bottle To sort-of body temperature cause a problem with their stability and They hadn't really looked to that but on it.

00:25:06: i Know That The bottom once It's the sister drops Is is normally Once Its Opened its kept outside at room Temperature?

00:25:15: It doesn't need to be kept in the fridge.

00:25:18: So that's one sort of advantage.

00:25:20: It can cope with a warmer temperature, but the bottle obviously gets replaced at end-of-the week for new ones.

00:25:29: Yeah and... Oh sorry!

00:25:31: No no, carry on Rachel.

00:25:32: yeah I don't want to interrupt you.

00:25:34: i'm sure we have some further things to say about it?

00:25:39: Well my apologies.

00:25:43: what is coming out are differences in the two that are commercially available.

00:25:51: Just recently, Cisteran which is as you introduced... The more liquid version-the one that's commonly used in the United States has been tested and found to be not need to remain refrigerated.

00:26:06: so once individual bottle is open.

00:26:09: So that's actually very recent and good to know update, makes it a little easier for people carrying them around.

00:26:17: so just thinking about what's useful for people to know about the differences between these two drops.

00:26:22: I think we've talked a little bit about differences in putting them in the eyes.

00:26:27: you had mentioned this sister drops.

00:26:29: the thicker ones are needed less frequently.

00:26:33: they're tested and approved four times per day Whereas the sister ran, as I was explaining very typically six to ten times a day.

00:26:41: Often six-to eight being very fine and so i think people can... People we know have good success in both formulations..I will say that some are more comfortable with one over another.

00:26:55: there are not so many patients who have had the benefit of trying both but personal response.

00:27:04: Some people feel that one version stings a little less than the other one, or one is a little easier then the other.

00:27:11: in a perfect world-people would have choices and end up with the ones most comfortable.

00:27:16: but I think we're just glad to see some options.

00:27:20: Is there anything else?

00:27:33: people are aware of.

00:27:35: I think a little bit more with the sister drops than, um... With The Sister-Own or The Aqueous Formulations.

00:27:41: is that there Is a Little Bit More Of An Effective Blurring Of Vision Afterwards?

00:27:49: Um.. I mean We Are Talking Probably A Matter Of Minutes Rather Than You Know A Long Duration Of Blurred Vision.

00:27:56: But i Think That's A Product or a function of the fact that the viscous drops are, you know... ...a little bit thick on the surface of the eye and will cause some blurring off the vision.

00:28:12: And anecdotally I think some patients may find that the stinging effect of the eyedrop lasts a little longer with the viscus formulation than aqueous formulations, but it's very variable isn't.

00:28:29: and you're quite right Rachel in that there is a lot of Inter into individual variation In how the side effects are perceived by patients By children.

00:28:44: so some You know.

00:28:45: when I've asked some children they sort of say.

00:28:49: They don't like the stinging.

00:28:52: Most Of The Children i've seen on sister drops, I think they're more upset by the thick gloopiness of the viscous formulation.

00:29:04: More than the stinging actually.

00:29:08: So you know.

00:29:10: and then there are some who just absolutely fine with it.

00:29:14: They have no problems but quite happy And i don't what is that makes one person more tolerant to them?

00:29:23: I don't know, have you got any ideas Rachel?

00:29:25: Biological diversity.

00:29:27: We're so grateful for!

00:29:30: Yeah absolutely The next thing we were going to ask and talk about was how often they should be applied.

00:29:37: but we actually touched on that Did do anything else too?

00:29:42: You said Rachel, you said sister Anne six-to ten times a day can very effective.

00:29:48: Once you've started someone Let's say, you know they're on ten times a day and They are having a good response To that ten times the date.

00:29:59: Do you tell them to?

00:30:01: Reduce the frequency what do you?

00:30:03: What do you say?

00:30:05: Yeah, so that's a great question.

00:30:07: I Adapt the recommendation based on how they're doing.

00:30:10: So if we have a new patient who has a lot of crystals and we have different methods Of scoring but the studies that originally led to approval at the NIH The NIH Studies of the first sister amine eye drops Used a grading score where photos were taken?

00:30:29: And then these photo standard photos the gall scale was compared against the kind of like a legend that went from zero to three anyway.

00:30:41: We have different methods now, but we still do those photo comparisons.

00:30:46: so if somebody came in and I give that context only because If you had a score of three That meant You had A lot Of crystals In The eye?

00:30:52: That Would be a patient.

00:30:52: i would Be trying To Have them use drops ten or more times a day for that first year And I would see them more often in that first year too, as we're getting them accustomed to the routine and making sure they are able do their technique properly.

00:31:08: But then say you clear down a point five which is well tolerated by patients who will not hurt your eye long term.

00:31:18: We'd be very happy with it.

00:31:20: They might maintain this at just six drops of day.

00:31:23: So exactly right?

00:31:24: It's no one done recommendation in terms of frequency and so I think that can change over time.

00:31:35: Yeah, there's a similar story with the sister drops.

00:31:40: they've done studies.

00:31:44: it might have been the OCT-I study which used or didn't rely on just the girl school.

00:31:56: In fact, it was using primarily the in vitro confocal microscopy.

00:32:01: So it was grading crystals at the microscopic level within the layers of the cornea and they showed that initially starting the drops four times a day where patients had A positive response with reduced measures off crystal density on the in vivo confocal microscope.

00:32:27: They then followed up after a period of time by reducing the frequency, uh...by one drop.

00:32:35: and they reviewed again.

00:32:37: if it continued to reduce that would reduce the frequency twice today but increased there will increase the frequency against.

00:32:45: so they titrated according to the IVCM in V-vote confocal microscopy score And I think on average, by the end of that study patients were probably on average using it less than four times a day.

00:33:01: Probably in the region around three times per day on average.

00:33:05: so there may have been some patients who are using and managing to keep stability of their crystals at frequency twice a day but some might've relied on using for time today.

00:33:17: The sister drops was initially licensed to use To begin with and that's how we started off.

00:33:25: And in those patients where?

00:33:27: We can see it clearly good response.

00:33:29: We will reduce it By one drop

00:33:34: like a similar a similar practice pattern, so maybe we could get to the question That is naturally next which Is What do you expect in these exams Like How often and what are we expecting In the examinations of patients with cystinosis.

00:33:54: Do you want to introduce your thoughts on that, Suzmito?

00:34:00: Yeah so I think we will always start off with the basic stuff during examination.

00:34:07: So what i do is check their visual acuities With an age-appropriate visual acuity test check, and I don't know if you do this Rachel but i checked their contrast sensitivity.

00:34:27: And that's only because...I think the cornea is sensitive to haziness due to increasing crystal deposition problems with that over time.

00:34:44: Contrast sensitivity rather than just straightforward visual acuity a sensitive method of detecting real-life vision problems for these patients.

00:34:55: So, so contrast sensitivity is something else I measure and then you know we'll look at their cornea with the with the slit lamp.

00:35:07: um and i think that's...you know..the slit lamp examination is an important aspect talking about the different age groups.

00:35:18: The vast majority of children are absolutely fine having their eyes examined on a slit lamp, but you might find that infants and very young children may be a little bit more tricky to examine with this slit lamp.

00:35:30: um...and you can use uh..a handheld device.

00:35:36: But if-if you don't have a handhold device You can still hold a baby up against a normal conventional table mounted slit lamp by holding the baby in a sort of superman position, flying baby position.

00:35:50: And usually you can get very good luck at their corn ear even for few seconds because the St.

00:35:57: Lampe is such great device for looking like corn ear.

00:36:01: You often got quite a good view what's happening with your crystals So that I think would be the minimum surface disease, erosions.

00:36:18: Obviously look at things like eyelet eyelashes eyelid margins Conjunctiva and that sort of thing taking all back into view.

00:36:28: but I think we just discussed about trying to see whether we can document these things as accurately as possible.

00:36:37: crystals in the cornea.

00:36:39: We mentioned if the instruments were available, photographs of the cornea.

00:36:46: So you can use the garl scale more effectively.

00:36:49: so it's something that is a tried and tested method of assessing corneal crystals.

00:36:57: The garl-scale using photographs can be very helpful particularly in younger groups And then I find that using anterior segment OCT is a quite practical way and well tolerated of documenting crystal deposition in the coroner.

00:37:17: It's quite quick, painless relatively totally non-invasive way... ...and well tolerate by even very young children And it can identify crystals easily with ease.

00:37:37: So I think if you have an anterior segment OCT, even a posterior-segment OCT device can be used to look at the anterior segment these days.

00:37:49: So we don't have to particularly purchase especially designed anterior-segment OCT because many posterior conventional OCTs for looking in the retina are adapted to use of the anterior segments.

00:38:04: Of course there other instruments that can be used with increasing difficulty, so we as a matter of routine do densitometry.

00:38:15: Some OCT devices have dense tometry built into it and thats nice objective way measuring crystals.

00:38:23: there's no interpretation required.

00:38:26: the examiner software within instruments does all for you.

00:38:32: IVCM in vivo confocal microscopy has been used In clinical trials.

00:38:40: So some of the Trials that were used for the sister drops.

00:38:43: I mentioned earlier Used in Vivo confocal Microscopy, but in reality This is not a very practical instrument to use in your nor practice Our daily practice because it does require contact.

00:38:57: at the moment contact with the cornea.

00:39:00: Non-contact devices are being developed, but they're not on the market as yet.

00:39:04: As far I'm aware.

00:39:06: But if they do become in a market that might provide an additional means it probably will come at a cost i suspect.

00:39:14: So i'm just thinking about practical things.

00:39:18: i'm sure Rachel you've got plenty to say About what?

00:39:20: You can Do practically To examine these children.

00:39:23: What do you think?

00:39:25: Well, I think you've covered it that the punchline is You do whatever.

00:39:28: You can get out of the exam.

00:39:30: and What i find Is helpful about?

00:39:36: The images whether It's a photograph or the OCT.

00:39:39: And for the families listening in patients listening.

00:39:42: the nice thing About the techniques That susmito described.

00:39:45: they are non-invasive The light burden tends to be very well tolerated and they're quick, so these are great devices.

00:39:54: But to be able... I'm thinking of one my patients in particular at NIH when i was image looked like, it's quite impressive.

00:40:08: So we see it all the time.

00:40:09: but the patients don't always have to benefit.

00:40:11: so be able show them.

00:40:13: and then when I showed him what it looks after he had worked really hard almost a year with the drops in how much improved picture was not only did you feel better seeing that was so motivating.

00:40:25: being able use imaging technologies is helpful for families or patients.

00:40:32: all this hard work is paying off, both on how they're feeling but also medically what the images of their eyes look like.

00:40:39: You know, and I would add in terms of exams one Of the things that is important in the eye exam And the reason we want to do this exam at least every year In every patient with cystinosis Is that it's not just The front-of-the-eye.

00:40:52: so if the crystals are well controlled?

00:40:54: And the drops Are being used.

00:40:55: Well We still do need To continue seeing the patients because there are changes That happen inside the eye that we Need to screen a monitor for two up those our If crystals accumulate.

00:41:09: Pardon me.

00:41:10: If crystals accumulate in the retina, which is back neural tissue of the eye whose job to receive vision signal and then send it onto brain if crystals accumulate there they can damage that tissue and lead to vision loss.

00:41:26: this part of the I actually served by blood vessels need medicine given.

00:41:38: Systemic medicine is needed to protect the eye, not just the eyedrops.

00:41:43: So it's very important that patients serve on both.

00:41:45: The reason the eyedsrops are also needed because of the front surface of the eye—the clear cornea we're talking about does not have its own blood supply and lucky for us, eyedrops do a great job at getting into that tissue.

00:41:58: but the retina is only protected when the medicine is in the body.

00:42:02: so it comes through with systemic therapy.

00:42:05: And if a child is well-managed, then they will not have problems with retinopathy and loss of vision because damage from the crystals in their retina.

00:42:13: However... If that has been inadequately controlled there can be retinopathy!

00:42:17: That's important to detect on exam.

00:42:20: The second thing that's important for an exam is swelling of optic nerve.

00:42:25: The optic nerve connects the eyeball to brain.

00:42:28: This swelling happens even patients who are well-controlled both with systemic meds drops.

00:42:35: We call it papillodema, and its a swelling of the nerve that can damage nerve tissue and lead also to vision loss.

00:42:42: there are treatments for that.

00:42:43: we can manage but only if you know what's happening.

00:42:46: sometimes it could be associated with headache which is why your leave visit.

00:42:58: Yes, please see your ophthalmologist.

00:43:00: Make sure you're seeing them once a year.

00:43:01: even if you are being told that your eyes look great and you have no problems or symptoms when playing nice sports in the sunshine while tolerating it all You still need that yearly eye exam.

00:43:13: I

00:43:15: think fully agree with everything you said particularly around making sure there is no posterior parts of the eye getting involved the back of your eyes, not getting involved.

00:43:29: I think that point you made about patients and young people having a look at photographs with their own eyes is really important And i too have experienced both patients who've had positive effects from being very good you know, putting their drops in and taking the oral medications.

00:43:56: And being able to demonstrate to them that things are clearing but in a corner of the retina looks healthy.

00:44:04: they're doing really well.

00:44:06: Similarly even patients who haven't been great at using their drops or have not particularly good with their oral medication.

00:44:17: I've come across patients whose pictures were shown.

00:44:23: that's what my eye, and it does become a motivator from this point of view.

00:44:29: They suddenly realise there is actually physical effect which they may not have been aware off.

00:44:36: Of course they might have symptoms with photophobia or some ocular surface discomfort but they may be unaware physically caused by these deposits in the coil.

00:44:50: when they see that then suddenly just changes their perspective on things and you know hopefully translates into better use, more regular use of the eye drops.

00:45:03: so I think feedback is really important for them.

00:45:13: We covered how we assess the crystals and how we rate the effectiveness of treatment.

00:45:21: I'm going to move on to next question, Rachel... ...and ask you what are the consequences of not using eye drops?

00:45:32: Oh yeah!

00:45:33: The default is that these crystals accumulate in all tissues of their eyes In the simplest form of knowing about it, it can lead to complications that cause both discomfort and also vision loss.

00:45:48: So like... That's just a punch line up front.

00:45:51: It-it can cause scarring on the surface of the eye, scarring in internal contents.

00:45:56: so there is a form of glaucoma when fluid doesn't drain properly into anterior chamber Of course retinopathy which could lead to vision loss because the retina tissue isn't receiving the vision signal.

00:46:11: So all structures of the eye can be damaged through accumulation of crystals, very simply put.

00:46:21: The good news is when patients are well treated we rarely see these problems.

00:46:26: so this is really a matter of adherence to therapy.

00:46:32: We're very lucky if you have treatment.

00:46:35: Yeah absolutely and I think it's interesting isn't that?

00:46:39: because since Systemine has come onto the scene in the early two thousands, wasn't it?

00:46:48: We now see very few people with genuine retinopathy these days.

00:46:55: And that's quite different from previous experience of this condition prior to treatment being available where retinal involvement was inevitable for a vast majority patients as they got older.

00:47:11: So this has been a real game changer, hasn't it?

00:47:15: As far as the eyes are concerned and similarly with the eye drops.

00:47:20: It is a game-changer The important thing to recognise when these problems occur because they very rarely happen in ten years of life, or even in the second ten years.

00:47:43: It's really when you're in your twenties and thirties that a history not using your medications starts to have negative effect on your eyesight.

00:47:59: The clear window at front of the eye starts to lose its clarity Your contrast sensitivity starts your retina may start getting involved, so your peripheral vision might start getting affected.

00:48:13: Your visual acuity may start reducing as a result of these complications accumulating.

00:48:23: So I think that for me the message is important That in your teens particularly when you are getting autonomy, you're starting to take control of your own destiny.

00:48:41: Your own medicines and that sort-of thing.

00:48:43: You may feel it yeah everything's okay with my eyes but actually what you are trying to do is invest in your eyes by being as good as possible can with compliance with the medication because...you don't want get into a situation where you were in your twenties or thirties where your vision is really now starting to get affected by the complications of having long-standing crystals accumulating in your cornea.

00:49:16: Would you agree with that, Rachel?

00:49:18: Yes I fully agree and my only fear.

00:49:20: if someone hears this message they should not misinterpret it thinking nothing bad can happen before their twenties... The symptoms of crystal accumulation And the photophobia can prevent, of course we know this.

00:49:33: Can prevent the kids from enjoying a good social life and active life as sporty life.

00:49:38: So I think that message you're sharing is Be diligent!

00:49:50: The second message was shared earlier.

00:49:52: You don't have to be frenetic about starting at super young age before one or two But just be diligent.

00:49:59: establish patterns, and a little bit is better than nothing.

00:50:03: And a little more's better then the little

00:50:04: bit.".

00:50:05: So if what you can do is twice-a day because that's your life doing right now don't say I can't do ten times of days so i'm not doing it at all.

00:50:13: Do the twice-A Day.

00:50:15: That will become second nature when brush your teeth or whatever.

00:50:17: Then add the third time.

00:50:19: Just build these patterns...I think this way helps people.

00:50:25: You know, and I'm aware we only have a few more minutes to share our thoughts with our audience.

00:50:32: It's just me doing one thing...I wanted to make sure when we talked about eyedrops was that we sometimes recommend lubricant eye drops And I just wanted to say a word on that and hear your thoughts.

00:50:46: Lubricant eyedrops are commonly used by people who have no eye disease, they just have little eye dryness because their on screens alot not blinking as often.

00:50:56: so lubricant eyedsrops you can find in over the counter pretty much everywhere.

00:51:02: Patients with corneal issues with crystals could have drier eyes than the normal population.

00:51:10: So if somebody is having eye irritation, I will often recommend lubricant, preservative-free lubricant eyedrops and they can be used a little bit before this cis-damming drops go in.

00:51:21: I don't like it to immediately because it dilutes effect a bit.

00:51:26: we would believe that could be the case.

00:51:28: but If thats what's required make more comfortable its worth.

00:51:31: have combination even if we are going to dilute to enable the child or young adult, or the adult to tolerate the drops.

00:51:41: So that's something nice to have in our armamentarium.

00:51:44: Something you as a patient and family member can discuss with the ophthalmologist.

00:51:47: hey should we test it for dryness?

00:51:51: Should be using lubricant drops?

00:51:54: I don't know if there are any final thoughts.

00:51:56: Susmeeta maybe didn't come up on this discussion

00:52:04: also prescribe lubricants before and after using the eye drops.

00:52:10: I make sure that they don't put it in immediately for straight-after, so at least... Well anecdotally like kind of say you know twenty minutes before or twenty minutes afterwards there's a good time to have an effect.

00:52:28: It may provide a little bit cushioning on the surface offset some of the stinging when you put the eye drops in, but also probably if you provide a nice environment for the epithelium to heal.

00:52:44: The sensitivity of the eye having things placed on it like the sister drops or the systemine drops is reduced as well.

00:52:55: because can imagine someone who's got poor ocular surface where there are erosion putting the sister drops or the sister and eye drops, can just hit those corneal nerves a little bit more readily.

00:53:11: And make it feel a little uncomfortable.

00:53:14: so I think the lubricant drops are really helpful and fully agree with your recommendation.

00:53:30: some take-home messages, can't we?

00:53:32: At this point given the... We've covered probably lots of things around using eye drops and different eye drop formulations.

00:53:40: And what else to look out for?

00:53:43: so you know I'm sorry one more thing came to me as you were talking.

00:53:48: What haven't talked about yet is preservative free eye drops or compounded eyedrops.

00:53:54: maybe could say a word.

00:53:58: Some people are sensitive to the benzalconium chloride that's used as a preservative in both sister drops and sister ran.

00:54:08: Compounding pharmacies can make sister amine eye drops using kind of a cookbook formula for this, we of course cannot validate a pharmacy that hasn't been inspected or such.

00:54:21: but do know that patients whose corneal disease is well controlled on compounded drops.

00:54:28: So really the effectiveness is tested in patient response itself, so if you have a child or yourself are allergic to this preservative do seek talk with the ophthalmologist about getting compounded drops that has no preservatives.

00:54:47: but then of course follow-up exams will be able tell whether particular formulation But it's not gonna hide if its working well your exams will continue to be good.

00:55:01: and If It's Not Effective Then An Adjustment To Therapy Will Need, To Be Made but Just To Be Aware of That.

00:55:07: Yeah Agree I mean we before sister drops was Was Available We Only Had Compounded Pharmacy Prepared Eye Drops.

00:55:16: And You Know There there is always going to be you know A challenge Around Stability For These Eyedrops Because As You Know Systemine Is a is a very unstable compound in the presence of oxygen and sunlight, has to be prepared very carefully.

00:55:34: And what we know from you know that the cistern and the sister drops are these have gone through a very rigorous process of manufacturing stability as being tested.

00:55:48: so they're pharmaceutical companies putting their best efforts you know, stability for the period of time where the drop is indicated.

00:56:00: This is course more of a challenge from compounding pharmacies and they don't necessarily have the ability to check these.

00:56:08: but we do know that this work as we've seen them from patients who being on these treatments prior to availability of the licensed products.

00:56:18: so it may work As long as your able put in effectively look after the drops, you know keep them at a right temperature.

00:56:28: Keep them away from sunlight or that kind of business.

00:56:31: but it's more of a challenge But absolutely have to have an alternative if benzalconium is not tolerated by patients.

00:56:42: And I guess, I'm just coming up with all my last thoughts as we wrap-up.

00:56:46: One more thing that i think would want to tell people who have cystinosis or are caring for a family member is the community groups...the patient advocacy group.

00:57:00: and there are groups in Europe.

00:57:01: they're groups from United States.

00:57:04: these groups wonderful to join to become informed, to meet other families and patients.

00:57:12: I would encourage anybody newly diagnosed with cystinosis or any family who has a newly-diagnosed child with Cystinosis to get online And I don't know anyone who hasn't benefited from getting involved.

00:57:33: Sometimes there are even scholarships to be able attend the family meetings if funding is an issue-to-go, but going once just at beginning meet other parents or people like you that have a condition and can talk about it... It's very helpful!

00:57:49: That would my little plug before we give some final take home messages.

00:57:56: Yeah, no absolutely.

00:57:57: It's a rare disease doesn't it?

00:57:58: and patients might feel a bit isolated on their own if They've been diagnosed with this and they're not.

00:58:06: if the if you are able to plug into Patient support groups that can be immensely helpful.

00:58:14: so yeah I absolutely agree with that.

00:58:17: So maybe we will go to our take-home messages.

00:58:25: What's your first-taker message, Rachel?

00:58:29: I guess the one that i like most is start treatment as soon you're able to even before symptoms.

00:58:39: For sure before you have symptoms balanced by don't make yourself crazy as a new parent understanding this is hard and give yourself some grace.

00:58:49: That's my message number One.

00:58:51: what about You?

00:58:52: Yeah thankyou for that.

00:58:56: the other messages that you know, as you quite rightly said and you've said various times in this podcast.

00:59:02: Systemine eye drops work um...and uh..you can if your diligent using them You can reduce And even clear The crystals in your cornea.

00:59:13: So thats a really good positive point to make about these eyedrops Anymore from you?

00:59:20: Right, sure.

00:59:21: Yeah oh I can't...I mean totally clear.

00:59:23: we've had patients who went from a three to zero.

00:59:25: i just have to say this is true This is at NIH and I was there And I saw it and It's a beautiful thing.

00:59:31: so I fully endorse your favorite point um..i would Say Point number Three see-your-eye doctor yearly.

00:59:42: You might Have more often than yearly At the beginning.

00:59:44: you Might need if its More Often Than Yearly but at least See Your Eye Doctor Yearly.

00:59:49: Very simple formula, live by that one.

00:59:53: And what about your next one?

00:59:55: It keeps

00:59:56: us in business as well Rachel doesn't it?

00:59:58: and...

00:59:59: This is a rare disease!

01:00:00: That's not going to keep this in business.

01:00:01: we want to keep our patients healthy.

01:00:05: So the other thing obviously again its just all about eye drops.

01:00:11: clearly the nephrologists will be prescribing systemine orally But remember, the oral system is doing good to your eyes as well.

01:00:21: It definitely reduces problems related to back of eye.

01:00:27: retina can keep healthy long-long term for rest life.

01:00:34: if you go with your oral system that gets very nicely into the retina because it has a great blood supply.

01:00:41: so what taking by mouth getting there effectively must must take your oral system.

01:00:50: Yes, and we have seen our patients.

01:00:52: Susmeita!

01:00:52: We've been following our patient in their teens...in their twenties...in the thirties....in their forties.

01:00:59: I mean new parents.

01:01:01: Patients with sister-nesses who have families of their own.

01:01:04: It is so exciting it's so beautiful.

01:01:06: So keep you eyes healthy guys You're gonna need them.

01:01:13: Thank you Rachel.

01:01:14: that's

01:01:15: brilliant

01:01:17: Thank you.

01:01:17: No, no I've enjoyed it and yeah i've learnt a lot.

01:01:20: so thank you!

01:01:22: It's always fun and come join a meeting.

01:01:25: maybe you'll see us.

01:01:26: audience.

01:01:27: who is listening?

01:01:28: please don't be isolated.

01:01:29: Please don't think that your the only one with this.

01:01:32: Find others And we hope to meet each other at family meetings in the United States or Europe.

01:01:36: Best of luck To all of you.

01:01:39: Thanks for watching.

01:01:42: If you'd like to learn more, the Cystenosis Foundation offers further podcast episodes and videos that provide helpful information and support for everyday life with cystenosis.

01:01:53: Do take a look!

01:01:54: And see in next episode.