Ep 48: Approaching eye involvement in rheumatic diseases

In this podcast, join Dr Stephanie Gall (Rheumatology Registrar) with her guest Dr Nima Ghadiri, a consultant Medical Ophthalmologist at the National Behçet's Centre of Excellence (Liverpool). In this episode, common eye presentations to rheumatology clinics are covered, including discussions regarding ophthalmic manifestations of rheumatic diseases and recommendations for investigation and management of eye disease presenting to rheumatologists.

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Transcript

SG - Welcome to BSR Talking Rheumatology Spotlight today where we'll be discussing ophthalmic manifestations and rheumatological conditions. I'm Dr Stephanie Gall, I'm a rheumatology registrar. I'm pleased to be joined by Dr Nima Ghidiri who's a medical ophthalmologist at the Liverpool University Foundation Trust. He's also an honorary clinical associate professor at the University of Liverpool. We work closely with Dr Ghidiri as he's a medical ophthalmologist at the National Bechets Centre of Excellence in Liverpool. Thank you so much for joining us today.

NG - Thank you Stephanie, pleasure to be here.

SG - Lovely to speak with you. I wondered if we could start with some broad topics today, so I wondered what are the common eye conditions we might see in the Rheumatology Clinic?

NG - Well I think there's quite a few eye conditions that you might see, in my patch of medical ophthalmology specifically ocular inflammatory diseases in particular there's there's a number of patients whom I share with rheumatology possibly more than any other speciality and any rheumatology trainees will have seen one or many of these in their clinics. So I think the common conditions or the ones that we will see described and referred the most often are uveitis, so whether it's anterior intermediate to positive otitis, These might be patients who haven't actually seen an eye specialist yet but will be describing their symptoms within the rheumatology clinic which leads to better clarity on their diagnosis. There's other similar inflammatory conditions which can present near the front of the eye such as scleritis or episcleritis, even further towards the front of the eye in the cornea there's manifestations such as keratoconjunctivitis, sicker but some rheumatologists might also see orbital inflammatory diseases of different sorts and diseases which can affect the back of the eye such as retinal vasculitis or autoimmune retinitis or ischaemic optic neuropathies that you see in conditions such as joint cell arthritis, so there's a whole gamut of potential conditions which can be seen in the rheumatology clinic which may or may not be known to the eye specialists in the same hospital.

SG - Yeah so there's lots of things that we could see and so integral questions what we should be asking about when inquiring about the eyes of Rheumatology what questions would you suggest?

NG - It can be a challenge with patients especially when they have vague symptoms and some symptoms which come and go in particular but I think that the key symptoms that you can screen for in rheumatology clinic which will be very useful especially when referring to an ophthalmologist are pain and particularly with the pain, how severe it is so a grade of one to 10 is useful of course, worse on eye movement as well just to help skew towards a particular diagnosis. Redness, sometimes the patient might not have red eye but might have photos of red eyes and it's useful to have a look at them and just see whether it's diffuse redness or localised to a particular part of the eye. Vision changes subjectively so when the patient themselves are describing sudden loss of vision is important, whether they're describing or blur vision at all is of course crucial, but even symptoms such as floaters or flashes and floaters can be useful for an ophthalmologist or anyone who's assessing the eye symptoms to gauge how quickly they need to act. A particular symptom which is useful is photophobia or light sensitivity which is very important in conditions such as UVI but also can be in other ocular surface entities as well. On that subject here dry dryness and grittiness can help unmask dry eye conditions but also discharge as well so watery discharge or epiphora important and purely discharge in infections and some very severe autoimmune entities. So those kinds of symptoms are very useful but also laterality is crucial as well so whether it's unilateral bilateral, whether it's acute or chronic, whether there's other things which might be red herrings in terms of rheumatological conditions, so for example contact lens use, whether what you're seeing is an infective aetiology and then find like in any past history past ophthalmic and past uveitic history is very useful as well so whether there's been a history of that of any autoimmune disease in general but especially if there's been any ocular inflammatory disease is important.

SG - Okay thank you so much that's really useful. In terms of the conditions that we see, I know obviously if I saw somebody with a sudden loss of vision I'd be referring to the ophthalmologist urgently, but are there any other red flags that we might pick up in rheumatology that would be an irritable to yourselves?

NG - Yeah, you mentioned just there the sudden pain, sudden painless or painful loss of vision, both of those are what I consider to be a red flag. From a rheumatological perspective a severe eye pain with redness, the things we would all be thinking of are uveitis and scleritis of course, then if the light sensitivity is also by a visual disturbance I would consider that to be something which needs a more urgent referral to not thermology because it's more likely to be a ocular inflammatory entity. New onset flashes and floaters, if particularly if the patient describes a torrent of flashes of floaters then we're thinking in the context of rheumatological conditions whether there's been an increase or a new uveitis which is affecting the middle or the back of the eye. In terms of non-rheumatological conditions of course those symptoms can also happen with retinal tears as well but we'll just rule out an inflammatory episode which has caused those. For orbital inflammatory diseases which can be a manifestation of lots of rheumatological conditions such as anca vasculitis such as IgG4 related disease and various other things, sarcoidosis and there's probably half a dozen things which I could mention if I thought about them right now but with that the symptoms of proptosis so the eyes looking or one eye looking much more swollen than the other and pain, particularly pain on eye movements. Yep, so particularly in those instances want to rule out inflammatory disease or orbital cellulitis but I'm sure most rheumatologists are very familiar with the features of GCA but it's all underscoring them again: scalp tenderness, jaw claudication, headache and visual symptoms. But the amaurotic symptoms are sometimes which are not often thought about instantly when it comes to RI casualties so I do always want to mention to rheumatologists to think about amaurosis fugax, so it occurs on like vision loss as well in gca.

SG - Yeah that's a really useful one because we tend to think of more of sort of a thrombotic strain than giant cell arthritis but that's a that's a an excellent one to mention. When you see somebody in eye clinic how do you go about assessing the eye?

NG - We start with visual acuities, so when referring and this is a bugbear for off homology on call registrars when other specialties in the hospital are referred, patients, is it's always, crucial to have a visual acuity for which, even if you can't have a formal Snellen chart or logMAR chart, applications with the right correct distance on your on the phone or an iPad or a monitor can help give a visual acuity. So visual acuity is key and it is important for us to know quite how much the vision's reduced compared to what we might know or might not know about the patient before. Where possible, pinhole using a pinhole tool to isolate the vision itself outside things like medial opacities or refractive errors is important so that's something we do in the visual assessment clinics but if rheumatologists are able to do that that's great as well. Then after vision obviously is something which can be fed back from rheumatology colleagues. Pattern of redness as I mentioned can be useful so we're thinking of diffuse redness can be useful but diffuse is nonspecific so you know, even if someone's had a bit of a viral, conjunctivitis that can have caused diffuse redness. But, if the character of the redness and how, aggressive it looks and the colour can be important photos, of course, important as well if they're available. Sectoral is useful because then when you have a, say nodular episcleritis which is sectoral that that will help identify that as episcleritis rather than say more diffuse scleritis for example. There's one pattern of redness that you get with uveitis which is very useful which is called ciliary flush so it's a ring of red around the iris and that can be a very important tip when it comes to uveitis. Pupillary reactions are very useful so just to check for any optic nerve involvement of course as well so doing an RAPD and checking for constriction and also and also consensual photophobia which is a feature that you see in uveitis as well so both eyes being suffering if one of the eyes has uveitis in it. Then external examination you can still even just see if there's discharge from the eyes that's always useful feedback for the lymphoma and tell us if the lids are swollen or if the orbit looks really swollen, again those are useful things as well but obviously understandably there's certain things which need to slip up and I'll pharmac assessment so any feedback from this that you can give and of course those who still have their fundoscopes with them in rheumatology clinic, any indication of optic disc swelling or pallor or haemorrhage around the optic disc can be can be critical for us as well.

SG - That that was useful. It's really useful to know what, things we should be assessing when we're referring to yourselves and what things are useful to know. I wonder if we can go on to sort of more, specific, issues with the eye, so when we see patients with uveitis how does it typically present?

NG - Uveitis that we see in rheumatology clinics and that you might see in eye casualty, statistically speaking it's more likely to be anterior uveitis that presents with pain, with light sensitivity, photophobia and often blurring of vision, can present with floaters depending on the amount of cells but particularly if it's more cells which are escaping into the vitreous or if it's more intermediate uveitis in those instances the floaters will be more of an issue. Clinically you see the redness, the ciliary flush which I described the ring around the iris is very useful, a pupil which looks quite small and misshapen of the adhesions which form between the pupil and other structures around it something called synechiae can be a very useful feature as well for anterior uveitis. Other things I don't think it would be possible to see within an outpatient clinic. If it's the likelihood of them of the patient having a reduction in addition is higher for the posterior segment inflammation. So if it's uveitis affecting the back of the eye they're more likely to describe both the floaters and the reduction in vision as well. 

SG - Okay what, I know uveitis is something we will we will all see in rheumatology clinic, but what conditions of ours are we more likely to see uveitis in? 

NG - The most common systemic disease linked to uveitis is HLA B27 associated to uveitis, so relating to ankylosing spondylitis or axspa and sero negative spondyloarthropathies in general, those ones count pretty much fifty percent of anterior uveitis of which the other fifty percent we're not so sure what the aetiology is or a host of other things but you can also see in paediatric rheumatology clinics more commonly JIA related uveitis, that's specifically the oligoarticular subtype which is ANA positive, rheumatoid factor negative. This entity really reflects the importance of screening because patients who can sometimes have a rip roaring uveitis in the eye, the kids who have it, they often can be asymptomatic so the issue in those instances is only when the complications of uveitis arise are the patients diagnosed in places where adequate screening isn't available so something to be aware of for anyone who works especially in other countries where JIA uveitis is seen that patients will not present in the same way as HLA B27 associated uveitis which tends to be more painful and are life sensitive and then a host of other immune conditions from sarcoids to behcets, so one of those which are more focused on the eye it can also cause uveitis specific in the front of the eye but in general I always emphasised this to patients that, for whom we saw they had a diagnosis, uveitis is a spectrum of about 150 conditions and in fifty percent of people we never find the cause and in the other fifty percent it's always important for us in ophthalmology to ask questions and then in rheumatology if a patient still queries this or that then the sentinel ophthalmologist who might be able to find an answer by the by the nature of the uveitis that we're seeing.

SG - Well I don't think I'd appreciated it in over 150 different conditions.

NG - Yeah there's about 40 kind of broad umbrella entities but in terms of just individual conditions which can cause uveitis there's yeah there's it's really broad.

SG – Okay, going on to, scleritis and episcleritis, what conditions might we see these in in rheumatology and how do these tend to be managed?

NG - The condition of rheumatoid arthritis which doesn't tend to cause, uveitis in general is, linked to scleritis and episcleritis and not just rheumatoid arthritis but the GPA as well where there's some associated, anca associated with vasculitis and certain other conditions as well such as lupus and lupus like entities can cause both of these. This can sometimes be challenging to differentiate, scleritis and episcleritis. We do describe in scleritis the pain as being very severe and worse on eye movement but I've seen episcleritis that the pain is really bad as well. So episcleritis tends to be milder but not necessarily, often can be self-limiting, can be helped a bit with non steroidal or sometimes topical steroids. Sclerotic on the other hand tends to need treatment, often systemic immunosuppression and as I mentioned severe pain. The redness that you see in the eye has a kind of deeper hue to it, it's deeper and we call it violaceous, it's got a kind of purply red hue to it. In practice in clinic we, we give a ten percent phenylephrine drops where, that concentration of phenylephrine, blanches vessels in episcleritis, so a patient with episcleritis their eyes become white with that whereas in scleritis it remains red. So that's our kind of easy differentiator but the symptom pathology should, if you ask close enough questions, should hopefully help you tease out some the differentiation or also with scleritis people will tend to notice vision loss much commonly than episcleritis.

SG - In episcleritis and scleritis, say in our patients with rheumatoid arthritis, would you expect that to when the rheumatoid arthritis is under control, would you expect they're less likely to have the episcleritis and scleritis or can that come even if they've got quite well controlled disease of the rheumatoid arthritis?

NG - It tends they tend to be linked but not necessarily and it does depend on whether the nature of their systemic disease has changed a little bit or the immunosuppression they've been on has really controlled their scariest, for example, but not quite sorry that they're rheumatoid arthritis, in terms of the joints, but not quite the ocular manifestation. But you you're right in that in general flares of these diseases, the various organs which are affecting the body do tend to get affected at once it just does depend on how well certain treatments certain organs are being treated by an immune expressive which might work better in say the joints of the eye or the or the brain for example.

SG - I just wondered if we could talk about giant cell arthritis, so sometimes it's difficult for us to interpret as rheumatologists the ophthalmology findings unless it specifically says anterior ischemic optic neuropathy is there. I wondered what do you actually see at the back of the eye and what findings might you see in GCA that is affecting the back of the eye? 

NG - GCA can be a big challenge and ophthalmologists use some GCA as much as rheumatologists do to help us define the likelihood in the patient that we're seeing when they come in with exactly what you described the mouthful which is arthritic Arteritic Ischemic Optic Neuropathy when they do have that AION we often see a pale swollen optic disc so the nature of the disc edema is a little bit different compared to other causes of optic nerve swelling be they infective or autoimmune it's got kind of chalky white blood cells which does help us a little bit identify whether this is GCA or not. Beyond that a lot of what we rely on in terms of our investigations are other features such as visual field defects. So whether the patient's had a total loss in the affected eye or whether it's an just an altitudinal field defect, the symptomatology like we just described the amaurosis fujax and transient vision loss that's patients might get whether there's a diplopia or manifestations of cranial nerve palsy because of the giant cell arthritis which can be variable as well, those are some of the features that that that we might see. It's especially in people of the right age and the right risk factors often we just think of the risk of other things that we could be looking at and decide always it's much less likely to be to be say an optic neuritis or a central retinal artery occlusion or a non-arthritic anterior osteophytic neuropathy which would tend to cause more of an altitudinal field defect than this and doesn't have quite the same kind of texture or colour to the optic nerve which often has other features with the NIONS in terms of the appearance of the nerve which is which is often more crowded than the and the colour stiff. These kind of nuances make a difference with our assessments but really we are also just thinking oh we you know the key differential here is the GCA so we ought to treat or we ought to discuss with rheumatology colleagues.

SG - Okay yeah that makes that makes sense, it's it can be quite a tricky one and it's good to know that you guys find it tricky especially with the nuances of it as well. When you describe the visual field defects, is there any way that it tends to affect first as in does it affect sort of the area or inferior area or can it vary from person to person?

NG - It can vary a lot from person to person and also there's other manifestations of visual field defect that you can get with gca which can muddy the water a little bit. So for example you know often patients will get a visual loss in one eye and then they can progress the other and the actual field defect can affect the patient different ways. I've seen gca where as a red herring or as a consequence of the gca it was linked to a stroke in the other which caused a loss of vision in the corresponding half of the visual field in both eyes which are the manifestations in the visual fields with GCA but there is there's quite a bit of variability in terms of what we see both with the fields and with the back of the eye in terms of the optic nerve. And as I said the optic nerve appearances that I've described there the chalky white edema are more the findings are what we see with ischaemic damage so you would see other features in the eye which are indicative of, ischemic damage to small spots such as, adjacent retinal, whitening as well. So these are kind of features which are nonspecific for gca but if you, you know, if you see them then it raises your kind of barometer of anxiety I guess, but we know we know in general that some sometimes the other findings in gca aren't the best defined and you might not get any pathognomonic features in the patients in front of you.

SG - Okay that's really useful to know because it can be managing GCA and finding out whether it is GCAs, it can be can be really true. The things at the back of the eye are incredibly useful. I wondered if I could move on to biologics in uveitis. So, from our understanding, adalimumab has got the best evidence for working for uveitis compared to other biologics. But far as you're aware is there is there evidence to suggest that other biologics can be equally effective?

NG - Yes. As you said, the adalimumab tends to be what uveitis specialists use the most for non-infectious uveitis although use infliximab for a Behcets uveitis and increasing and is also licensed for ocular sarcoid as well. Really for in practice for me and for a lot of uveitis specialists in The United Kingdom there isn't that much between adalimumab and infliximab in terms of efficacy for NIU. I just come back from a meeting it was interesting just to see how different differently patients are treated elsewhere and based on access to treatment and their own national guidelines but our strongest evidence is on adalimumab elsewhere because of availability they might be more likely to use JAK inhibitors for which for at least for optimal inflammation there is some evidence but not enough strong efficacy evidence compared to the anti TNFs. Elsewhere we use tocilizumab. So tocilizumab is licensed for JIA uveitis and also as we know for GCA. Increasingly for inflammatory diseases it's being used effectively off label. So the IL-six pathway we describe the I l six pathway as one of the broadest when it comes to the cytokine cascade. So it seems to be, it seems to be a potentially useful target for various different inflammatory eye disease that we can't. Probably warrants a little bit of a closer review and with new anti IL6 molecules coming to the fore, I suspect that a tocilizumab will be potentially used more often. Even now over the last two years, they're using it more in thyroid eye disease in isolated cases around Europe. The other one is abatacept as well. So abatacept is in, has increasingly shown strong experimental data and where patients with non-infectious uveitis aren't quite responding as well as you would have hoped to anti TNFs, that seems to be another option after anti IL6. Those seem to be the latter at the moment. In other countries, they go to JAK inhibitors after AntiIL6 whereas we don't go to The United Kingdom. Of course, there's other things, in terms of adjunctive steroid sparing agents, the classics that we and yourselves have been using for many decades of methotrexate, mycophenolate and the calcineurin inhibitors which although have a kind of narrow therapeutic window do act very quickly at the top of the autoimmune cascade and we still we still we still use them obviously need a lot of monitoring and hoping again that there's the new the new workhouse in neuro inhibitors find an expansion in their usage and that we can use them a bit more for uveitis.

SG - Oh that's really useful, it's good to know there's that there's a used elsewhere and things that are looking promising for uveitis as well. Was there anything else that you wanted to discuss at all?

NG - Just to let rheumatologists know that we've got quite a bit of excitement with some new uveitis clinical trials, which, maybe, maybe, expanded to other autoimmune conditions as well. So there's combined JAK and TIK, inhibitor trial which is, which we're doing in uveitis now, looking at Brepocitinib, JAK inhibitors, baricitinib and tofacitinib are being used a bit more often in other countries than we than we are in The UK but to get that sort of combination which also looks at other pathways including IL23, IL17 which we know are affected in experimental autoimmune uveitis that that is quite exciting, so hoping that we'll have new kind of additions to the momentum in the future as well as new delivery systems in the eye as well so that perhaps we can isolate the ocular and the systemic elements of the autoimmune diseases and also ophthalmology in general is one of the specialities which is the most exciting when it comes to AI and what we call oculomics, so biomarkers for predicting systemic diseases through the eye. So hopefully we'll be able to diagnose more systemic diseases including particularly autoimmune diseases via imaging and different types of investigations which are eye specific in the future which can definitely help rheumatologists for the kind of most challenging cases in the future so that those two are the kind of watch the space element when it comes to ocular inflammatory diseases linked to rheumatology.

SG - Oh, that's really interesting. Thank you. Thank you so much. And thank you for joining us today.

NG - Great pleasure.