 So Dr. Jost is going to be talking to us today about floaters fatigue and forgotten insulin Dr. Jost has been the intern prepping all my cataract surgeries for the last three months He's done a fantastic job. A lot of you probably don't know him yet since he's sort of been hanging out at the VA But I think you're really going to enjoy him as a resident Because he's been very conscientious and a hard worker. So without further ado Good morning, everybody Thank you for coming So like Lloyd said Title of my presentation is floaters fatigue and forgotten insulin and these are the three presenting Complaints that a patient had that I just saw recently at the VA about two weeks back So patient named CS Chief complaint of dark squiggly floaters in the right eye He's a 62 year old male set a three-day history of these dark floaters that he describes in a squiggly line pattern Also accompanied with eye pain blurred vision in the right eye Patient states that he woke up with a painful eye also some tearing and crusting of the lids and some mild Photophobia no trauma to the eye Interestingly patient had been off of his insulin for two weeks prior to the onset of this He does have a history of poorly controlled diabetes. This is not uncommon for him He apparently went on vacation and just decided not to take his insulin with him Also, he noted that his eye pain was increasing at severity Patients past ocular history He denies any past eye problems. No surgeries in the past or trauma Like I stated previously poorly controlled diabetic Believe his most recent a1c in the VA system was over nine He's had two previous hospitalizations for diabetic ketoacidosis and he He admittedly told us that his blood sugars usually in the two to four hundred range also Significant in his history in 2005 at the Salt Lake VA. He had an admission in the ICU where he was severely septic The source was right shoulder osteomyelitis, which grew out methicillin sensitive staph aureus During that same hospitalization. He had an infection of his parotid gland, which also grew out MSSA and Somewhat unclear history of these pulmonary nodules that were sampled during that hospital stay But resolved after antibiotic therapy For this right shoulder osteomyelitis. He was on IV antibiotics for three months as an outpatient Also significant for fungal infection of the groin Recent dental abscess in which he did not complete his amoxicillin prescribed to him and some other medical history of hypertension high cholesterol and reflux disease No family history of eye disease Patient lives in Rock Springs, Wyoming. He's retired No IV drug use history. It's never been incarcerated never homeless medications include medications for reflux disease oral and insulin for diabetes Receive statin and spironolactone for high blood pressure. He has no medical allergies on review systems He complained of recent fatigue However, he was ambulatory still active able to drive from Rock Springs, Wyoming to the Salt Lake VA and also complaining of recent tooth pain More specifically, he denied any of the following fevers chills night sweats chest pain Skin rash myelogies arthralges On eye exam his visual acuity with with correction of the right eye was count fingers And his left eye was actually pretty good at 20 30 slight improvement on pinhole of the right eye He had no afferent pupillary defect as motility was full Interaction pressures are 9 and 12 respectively and his confrontational visual fields were full On slit lamp exam. He did have some mild ptosis of the right eye and some periorbid ol erythema His congenitivin sclera. He had two plus injection of the right eye He had some corneal edema and he's all actually bizarre linear keratic precipitates That none of us that actually seen before when we took a look at him at the slit lamp I have a picture of that coming up Also noted some gutata on the left eye. He did have three plus cell of the anterior chamber of the right eye and as Our excuse me that should be left eyes quiet He also had some pigment on the interior lens capsule the right eye So hopefully this projects well, but there's some linear Precipitates here on the cornea and initially we believe that these were actually on the anterior and posterior surfaces of cornea Not the best picture. This is an iPhone slip lamp photo Here's a more zoomed-in picture. Thanks to Tom oberg for taking these he's really great at that You can see these linear. They're kind of brownish golden in appearance On fundus exam. He had three plus vitreous haze three plus vitreous cell the right eye And from what we could see there was an elevated white lesion with overlying hemorrhages in fear to the optic nerve The lesion appeared to be sub retinal and elevated and they were scattered mid peripheral dot blot hemorrhages Probably secondary to his poorly controlled diabetes So here's a photo from what you can tell the fundus Landmarks are obscured. It doesn't project very well on the screen, but maybe optic nerve under here in a White elevated lesion Actually on indirect ophthalmoscopy. You could see a lot better than this photo shows So from now This patient was seen at the VA. We wanted to send them here to the Moran. We had to come up with a differential So broad differential of pan uveitis. He had inflammation of what appeared to be all chambers of the eye Just to break it down. You have infectious causes and non infectious causes typical bacterial players fungal parasitic organisms like toxoplasmosis other Viral etiologies that can cause necrotizing viral retinitis tuberculosis syphilis and With patient with an unknown immune status. You always have to think of It's a quality of HIV infection Although cmv doesn't typically present as an elevated lesion the view wasn't Good enough for we could say this was clearly not cmv Other possibilities include non infectious sarcoidosis masquerade syndromes Vascularities So our assessment was pan uveitis with the elevated peripapular retinal lesion Surrounding retinal hemorrhages and possibly sub retinal abscess of the right eye so Our work up an initial management consisted of he was sent here to the Moran urgently that afternoon Dr. Shakur performed a vitreous tab where actually took out One and a half cc's of vitreous It was sent for Gramstein culture fungal cultures These following were sent for PCR These were done here, and then also bacterium fungal PCR was sent to the University of Washington, which took a while to come back Vitreous was injected with Gans cycle veer vancomycin Cytasin and clindamycin Did not know what was causing this so we wanted to cover all our bases And then initial systemic workup He came back to the VA for labs. He had a ppd placed HIV and hepatitis Panel was drawn test for syphilis test for sarcoidosis Basic lab work chest x-ray to look for any pulmonary nodules And also blood cultures were sent Also fungal blood cultures Patient was initially started on Bactrum a cycle veer and then cycle gel and prettiness alone topically So on the second day patient came back to clinic here his visual cutie had dropped A little bit to count fingers at two feet. Although he was subjectively feeling better That's a good sign for him. These interestingly these linear keratic precipitates had disappeared overnight Which confused us even more since we didn't know exactly what was causing them And then it initially Additionally, intravitual injection with voriconazole was added to cover for fungal Um Gave him a couple more medications of voriconazole and azithromycin cover for fungal and Also cover for toxoplasmosis So here's a picture. I just wanted to show that these keratic precipitates had disappeared Here's a Fibrin plaque on the interior lens capsule that appears to be resolving Maybe a small hypopia down here is difficult to see The zoomed in picture just showing that vibrant plaque and also some corneal edema And it's nice slip slip beam photo where it shows that those keratic precipitates were that are no longer evident So a better picture of the fundus A little bit better visualized on this day. You can see this fluffy raised lesion With some surrounding hemorrhages Another photo Basically showing the same thing So follow-up days five through eight We had a lot of our lab work back Which was nice to have he did show just a mild leukocytosis with a left shift Interestingly one blood culture came back positive for staph aureus We thought maybe this was a contaminant. Um, so we recent blood cultures Not really high SR, CRP Not super high either and actually all of his other systemic lab work came back negative ppd syphilis workup, etc The initial sensitivity of that positive blood culture revealed that it was methicillin sensitive staph aureus And then the repeat blood culture for still pending So two days later once the repeat blood cultures came back showed msa again Um, once we found this out. He was still ambulatory still feeling generally well Um, we saw him in clinic on a monday and he was sent to the VA for evaluation Of this bacteremia in the emergency department So medicine department evaluated him Decided to be admitted with this bacteremia. He started on naphyllin two grams every four hours To treat the bacteremia We discontinued a cycle here in bacterem. We discussed this with the primary team and we felt that this was the best option Uh, we did not think this was a viral etiology and the bacterem was not going to do the same job as as the naphyllin Infectious disease was consulted to help identify the source And because we weren't exactly sure that this lesion in the eye was caused by staff We wanted to make sure to keep on our fungal coverage Until uh, our final pcr is from university washington and came back negative Uh, actually his v it there's visual acuity on david mission would improve significantly to 2060 And you'll see throughout the presentation how that changes Uh, he had a trans thoracic echocardiogram, which is the initial test to look for endocarditis Um, this was negative for any vegetations But of course they had to do the obligatory of trans esophageal echocardiogram just with a higher positive predictive value Um, did show a two millimeter highly mobile Thickening of the aortic valve consistent with aortic valve endocarditis I wish I had a picture of the echocardiogram vegetation two millimeters is pretty small and i'm not sure how that would have projected up here Um, on fall up day day number 12 Uh, it's visual acuity like I stated was 2060 his exam was stable Um, zithromycin fluconazole was discontinued However, we did continue the topical therapy of the steroid to reduce inflammation and the cycle gel to Prevent any formation of posterior synecai A ct of his orbits and brain was obtained. Although we would have preferred an MRI to Better characterize the possible abscess in the brain or posterior to the orbits There was no abscess seen on the ct Patient did start to develop worsening renal function while in the hospital as creatinine I believe it was initially 1.1 1.2 range And bumped up to a high ones almost low twos range um A little bit conflicting thoughts on what was causing this but one one of the possibilities was that he was flicking off septic emboli to his kidneys Patient was uh Had repeat blood cultures, which were negative once they were negative for 48 hours He was discharged home on ivy antibiotics for six weeks at minimum So here's some better photos At follow-up appointment. You can see this almost boat shaped hemorrhage. Um, this fluffy vitreous Opacity that's protruding forward And some elevation of lesion as well Nice montage photo of the same thing Also some peripheral dot blot hemorrhages Here's an oct through the lesion You can see here that the retina is swollen or edematous Uh Coralite appears normal and intact and then this is a sub retinal lesion So the rest of my discussion today will focus on endogenous endophthalmitus Here's a nice, uh graph of the branching point between what we See more commonly is exogenous postoperative endophthalmitus But i'm going to focus on the endogenous causes which account for less than 10 percent of endophthalmitus Our patient would probably be classified as a diffuse case and posterior if you're going to break it down So endogenous endophthalmitus Due to a hematogenous spread of organisms Like I mentioned less than 10 percent of all forms of endophthalmitus are due to endogenous causes Um, all ages can be afflicted. Um, typically much sicker patients in general And that's why our case was quite unusual because he was ambulatory and carrying on with his daily life just fine Right eye is twice as common to be affected as the left eye The thought is there that it's the right carotid artery comes off theortic trunk more proximal location It can be bilayerally in up to 25 of cases Extra-ocular focus can be found in in up to 90 of cases, which I thought was a pretty high high number These top four here endocarditis meningitis skin and moon infections in pneumonia are more common in the world West Down here, hepatobiliary infections more common in the east Liver abscess is commonly seen in in Asia Some case reports of intradominal infections like iliosoas abscesses So CT imaging is is warranted in if your history dictates that risk factors for endogenous endophthalmitus clearly immune to compromise patients Not necessarily in severely ill HIV patients and Neutropenic and organ transplantation patients actually in a run-of-the-mill diabetic patients This number is actually pretty similar to the amount of diabetic patients. I have at the VA and And this this is a pretty strikingly high number of the The case series that I've that I researched Up to 50% of cases patients that had incombinant diabetes Other things that we see a lot of chronic renal failure malignancies Don't see so much HIV, but the obvious obvious risk factor for this Especially fungal causes IV drug abuse again another Player that involves fungal endophthalmitus People with valvular heart disease recent surgeries People with chronic indwelling lines and catheters as our patient did have for about three months. Go ahead, Jeff Yeah That was listed on one of the reviews that I did see but I didn't see a long discussion about the pathogenesis and how that is so I could view it as a immunocompromised state Also burn patients more susceptible to infections and patients with chronic antibiotic use Just to highlight a couple things that our patient did have diabetic diabetes poorly controlled Chronic indwelling lines and catheters, although this was many many years ago and also a long-term use of antibiotics So why diabetes just a quick review on Why diabetic patients tend to get more infections? There's an increase in a bacterium in general in diabetics, although the overall mortality is not higher The attributable mortality to bacteremia is higher in diabetic patients On the biochemical level some of the things that cause Poor immune function, neutral chemotaxis is depressed along with phagocytosis Bactericidal activity Cell-mediated immunity are all depressed in diabetes patients Specifically those with hyperglycemia as our patient has Specifically one thing methylglyoxal glycation. This is a major Cause of a glycemic damage in diabetic patients Specifically inhibits IL-10 interferon gamma tnf alpha from t-cells We all know that diabetics get vascular have vascular insufficiency This leads to some ischemia of local tissues and destruction and depressed bactericidal function of leukocytes neuropathy of Typically in the lower extremities leads to microtrauma and a An opening for bacteria to enter the bloodstream And then lastly, I think is actually most important in our patient cases that Skin and mucosal colonization with pathogens like staph like candida Is seen in a higher incidence in diabetic patients asymptomatically This would predispose them to transient bacteremia which is Possibly how our patient come came to develop a aortic vegetation So clinical features of it endogenous endothelitis Typical things you see with any infection fever Chills elevated white blood cell count left shift positive blood cultures Commonly ill patients hospital bound those in the icu Although we can see ambulatory patients as seen With our patient here acute and onset Blurred vision sensitivity to light Can see fibrin and you can see fibrin in the interior chamber with the route hypopion Bittress inflammation, which can be marked Retinal sub-retinal absceses Roth spots and also can present as a feared presentation of panophthalmitis with all layers of the eye involved To the pathogenesis briefly Micro microorganisms enter retinal circulation and lodge in small capillaries The areas of the highest blood flow in the eye Particularly the retina coroid ciliary body are preferentially affected In order to invade the tissues the pathogen must cross must cross the blood ocular barrier This is thought to be through direct invasion of septic emboli emboli and also changes in the vascular endothelium If the infection does spread into the vitreous it is Develops in the retina and then breaks through into the vitreous cavity And then the poor visual outcome that typically follow are due to the high inflammatory Cells in the in the vitreous cavity and throughout the eye and also through direct invasion of the organism Microbiology briefly Fungal is by far the most common Cause with Canada species being the most common fungal Canada species typically have a better prognosis and are more easily treated than things like aspergillus which tend to have a poor prognosis In terms of bacterial causes, grand positives are the most common with strep being The most common player here And actually staph aureus is more involved in cutaneous infections than you'd think of the endocarditis or Intraabdominal GI infections Gram negative bugs are also another feared Pathogen and these typically in general have a poor prognosis as well So I just wanted to highlight here that Staph aureus is what our patient had Risk factors that are seen our diabetes like he had started to develop some renal failure Did have some intravenous catheters in the past Although we didn't see any cutaneous infections in him does have a history of septic arthritis our patient does fit quite well with Some of these series that have seen similar patients Just a brief comparison between fungal and bacterial endogenous endothelitis There's a couple case series here that present Fungal versus bacterial Fungal in particular is more indolent slower growing Bacterial presentation is more explosive like our patient had More seen bilateral with fungal blood cultures Very very highly positive in bacterial endogenous endothelitis And here's a brief comparison between prognosis They called greater than 2400 A good prognosis in terms of outcomes And you can see that there's quite a range of of data in terms of who achieved better than 2400 Important here is that there is a very very significant incidents of either no light perception or just light perception vision So in terms of diagnostic recommendations I feel that we followed What's been seen in the literature either an aqueous of vitreous tap Vitreous tap and vitrectomy have a higher yield of organisms with Vitreous taps being cited as having up to 80% yield rate Although our tap did come back negative for all our test scent This is consistent with the appearance of the lesion being subretinal hadn't broken through into the vitreous So actually wasn't too surprising that our Cultures came back negative PCR can be useful Either panbacteria pan fungal primers those were the Test that we sent up to the university of washington to help make our diagnosis Things like fluorescein angiography B-scan CTs and MRIs of the orbits can be helpful if the diagnosis is still unclear in our patient We didn't opt to do B-scan just because our view was actually good enough where we didn't feel it was necessary to need a B-scan The role of the trectomy is still very unclear In the cases of endogenous endophthalmitis as as opposed to Exogenous endophthalmitis and important note is that the EVS study does not apply in terms of recommendations to this because it's endogenous So why why do we choose to do vitrectomy? Can provide additional material for culture removed debris from the eye And possibly better distribution of antibiotics. I don't think there's any great data to support that Outcomes are much better with vitrectomy In terms of systemic work up, of course, we always are told there's no substitute for a careful history, especially in patients with UVitis This can be aided by internist or infectious disease as we utilized blood and urine cultures HIV testing in patients with unknown unknown immune status chest radiographs echocardiogram Leading cause of endocarditis by far is staph aureus and patients with Staph bacteremia up to 30 of those actually have the order cardiac vegetations on their valves Intravitral therapy cover for bacterial pathogens thank myosin for gram positives Cytasidine or amacasin and gentamyosin to cover for gram negatives these last two amacasin and gentamyosin Have fallen out of favor somewhat just due to the potential risk for retinal toxicity And then also a careful balance between using steroids Our patient of note was not injected with dexamethasone In terms of covering for fungal pathogens amphotericin for econosal We chose for econosal as there is also some potential risk with amphotericin An important note is to avoid steroids when either fungal or viral Pathogens are suspect suspected, which is why I believe Dr. Shakur opted not to inject with dexamethasone Early treatment obviously is very important It's one study that shows better visual outcomes with treatment in That started 24 hours within diagnosis In terms of topical therapy This is less important however In terms of preventing posterior synechii secondary glaucoma topical antibiotic can be used if there's intense infection of the interior portion of the eye of keratitis Cycloplegics like I said to prevent synechii formation And if they start to develop secondary glaucoma ocular hypotensives can be used In terms of surgical therapy No great recommendations for vitrectomy Some things to consider when you would use a vitrectomy are Diffuse posterior cases Prominous vitreous involvement Patients that are not getting better despite this optimum medical management Especially virulent organisms like gram positives or excuse me gram negatives and aspergillus would be a good reason Why to choose vitrectomy Patients with poor visual cutie On presentation might like might benefit from a vitrectomy And then also I believe we got somewhat fortunate in this case with having a positive blood culture With all the rest of our studies coming back negative This might have been a reason why we Chose to do a complete vitrectomy in this patient if we wouldn't have the positive blood culture Other secondary issues that can develop our rental detachments holes and tears That need to be managed Either initially or later down the road In terms of systemic therapy This is better left to our internal medicine colleagues. However Cover for gram positives mancomycin is great for gram positives also MRSA Aminoglycosides or third generation cephalosporins which cover for Pseudomonas and gram negatives Um, and then once sensitivity is returned it's important to tailor your intravenous antibiotics appropriately based on cultural results Like I mentioned vancomycin MRSA IV drug users Napselin oxacillin are great choices for mssa, which our patient was placed on If fungal, uh If the fungal pathogen is identified in culture Amphotericin although we know that there's Quite a bit of toxicity systemically with amphotericin Other choices fluconazole or conazole caspifungin And then also important to Continue to cover for other players it could could potentially be affecting the patient We weren't sure initially viral or parasitic or fungal. That's what we kept those other oral medications on board Terms of complications down the road both systemic and ocular Every system can be affected obviously a patient with sepsis that Develop severe sepsis and shock potentially life-threatening Terms of the eye things like tractional retinal retinal detachment Hemorrhages in the back of the eye cataracts epiretinal membrane secondary glaucoma sympathetic ophthalmia Hypoteny, which is a poor prognosticator and also tisis Terms of prognosis a lot of conflicting data again Important to note that up to 10% of patients with fungimia have ocular involvement It's very important to keep in mind if you're seeing a patient in the hospital That's admitted with fungimia typically patients that are fungimic are Severely severely immunocompromised. That's why the mortality rate is so high Also goes to show that our patient didn't necessarily fit in with a lot of the studies That were published based on the severity of his underlying immunosuppression Visual prognosis is generally poor Some of the poor prognosticators Are those afflicted with more virulent organisms? Patients that are sicker in general delay in diagnosis The wide range of initially misdiagnosed cases And only about 50 percent of patients that present with endogenous and ophthalmitus are initially seen by an ophthalmologist Other poor prognosticators like I mentioned are obviously retinal detachment low intraocular pressure And uh worst visual acuity on presentation I mentioned aspergillus and gram negative associated with worst prognosis and staff actually Seem to be associated more with better prognosis, which is fortunate in this patient So in terms of our patient, I actually saw him yesterday in clinic at the VA His visual acuity has dropped a little bit to 2150 Although his uh on fundoscopic exam his hemorrhages seem to be dissipating somewhat He is on a home infusion pump and he was using it When I was there, he did have trouble with it last week where it broke Which I thought was It's perfect for him, but He is being compliant with his medications, which is very very important We will be following him weekly And uh important consideration for him any type of dental procedure Intraabdominal procedure. He's going to need prophylactic antibiotics Just because of his history And that's it. I want to thank Dr. Shakur specifically for helping me with his presentation And uh all the photographers that help get all these images up. So any questions? Thank you Let's start over here That's a good point. I know there are some value abnormalities Like excrescences that come off the aortic valves that could be seen as a possible vegetation I think maybe there's a chance that they over called this because of his bacteremia and they were quite worried about it Um, I don't have exact numbers of false positive rates. I do know Yeah, I thought it was important that the infectious disease people didn't just stop at at the echo once it was positive We initially additionally got the CT scan of the brain, which would have been better visualized with MRI He did I forgot to mention that he did have a dental evaluation uh Pretty early on in the course when we saw him we sent him over to the dentistry department at the VA and The dentist took what's that Yeah, the next day and the dentist wasn't really impressed with it But he did end up having a root canal a few days later. So it's kind of a mixed picture in terms of what was really causing it He did have a sore tooth and I was Yeah And we we think of we think of strep viridans as as one of the what we're taught is terms of Organisms in the mouth but staff and mssa and actually mrsa are actually seen actually in higher incidents in the mouth Then we once thought to you so True