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Further examination of three important cornea health topics
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I participated in the excellent Cornea Health Round Table organized and moderated by Terry Kim, MD, at OSN New York 2014. For those interested, OSN New York is held every fall and enjoys a great reputation for clinically useful information using a case study format. I will share a few more thoughts on the three core topics presented in the cover story: epidemic keratoconjunctivitis, toxic anterior segment syndrome and the MRSA/MRSE positive patient who is scheduled for cataract surgery.
As Jodi Luchs, MD, mentioned during the discussion, based on the experience of several clinical trials, the differential diagnosis of the red eye can be difficult, with many errors in diagnosis when clinical impressions are compared with definitive cultures and laboratory diagnostics. This is a potential problem because a misdiagnosed EKC patient can create an epidemic in an ophthalmologist’s office. It is wise for the front desk person to triage the patient with an acute red eye to a specific examination room. The patient with an acute red eye should not go room to room with multiple tests by multiple technicians because viral keratoconjunctivitis, especially EKC, is very contagious.
Useful clinical exam features pointing to a viral etiology include the history of a upper respiratory infection, a watery serous discharge rather than mucopurulent, a follicular conjunctival response rather than micropapillary, and the presence of a preauricular node. Still, the clinical differential diagnosis can be a challenge. The RPS Adeno Detector Plus is a useful test and has a 95% sensitivity and specificity. It is low cost and gives a rapid test outcome. If positive, I treat as viral conjunctivitis. Not all viral conjunctivitis is EKC, but I treat them as though they were. Because EKC is extremely contagious, patients need to be instructed to stay home from school or work for 2 weeks. This is a significant hardship, but an epidemic in a clinic or at a workplace is a disaster, and quarantines work, as we learned again in the Ebola epidemic.
So, now to some more controversial comments. I will tell you what I would do if I or my wife had probable EKC with a positive RPS. There is some evidence to my following thoughts, but everything to follow could be considered investigational and all is definitely off label. Is there anything that can speed up the resolution? I do not want to take 2 weeks off work or sentence my wife to 2 weeks of quarantine. There is some evidence that dilute Betadine (povidone-iodine at approximately 0.5% to 1.0%, Purdue Products) and Zirgan (ganciclovir, Bausch + Lomb) can kill the virus and/or shorten the days of viral shedding. If I or a family member had EKC, I would treat with dilute topical Betadine (it burns) twice daily to four times daily or Zirgan five times daily for 7 to 14 days. If my wife developed EKC, I would also treat myself with Zirgan, hoping to reduce the chance of getting the disease, and sleep in a separate bed, use a separate bathroom, use separate towels and wash my hands a lot for 2 weeks. Controversial, but this is a sight-threatening disease.
If I am treating with Betadine or Zirgan, I would also likely prescribe a topical steroid such as loteprednol or FML (fluorometholone, Allergan) four times daily to make me or my wife more comfortable and reduce the chance for subepithelial infiltrates, conjunctival scarring and corneal opacities. A steroid alone extends the period of time the virus sheds and can prolong the disease, but in combination with dilute Betadine or Zirgan, this issue appears to be mitigated. If treated with Betadine or Zirgan, I would recommend a quarantine for only a week, rather than 2 weeks. This is much more acceptable to most patients. For cleaning my lids, I would use a hypochlorous solution such as Avenova. It can be sprayed right on the open eye many times a day, cleaning away debris, enhancing comfort and maybe providing some additional antisepsis. So, if that is what I am going to do for myself or my wife, I should probably offer it to my patients, and I have.
Now, on to TASS in a family member. While the purist would say that all “endophthalmitis” deserves a vitreous tap, culture and intraocular antibiotics and that TASS is an “endophthalmitis,” after seeing many cases of both infectious endophthalmitis and TASS, I believe I can usually tell the difference. TASS presents the morning after surgery with no lid edema, minimal to no pain, a pretty pale/white eye, a very edematous cornea, a significant hypopyon out of proportion to the prior findings, and if one can see into the vitreous, no cells in the vitreous. Infectious endophthalmitis is often not diagnosed until day two or later, presents with pain, lid edema, a very injected eye, a clearer cornea, a smaller hypopyon, and cells in the anterior chamber and vitreous.
So, if it really looks like TASS on day 1 (and maybe I will have several cases), I will consider a therapeutic trial of intense topical steroid. I will use difluprednate and put in a drop myself every 5 minutes times four, add a drop of cycloplegic as well, and have the patient either stay in the office or go home and take difluprednate every 1 hour for 4 to 6 hours. I will also have them put in a fluoroquinolone antibiotic, but I am not sure this matters. I then bring the patient back to my office later in the day of postoperative day 1. If the patient has TASS, there will be a remarkable improvement. If the patient has infectious endophthalmitis, there will be minimal improvement or even progression. If in doubt, I will treat as infectious endophthalmitis, but I have seen TASS eyes in which the hypopyon has totally resolved and corneal edema improved significantly in 4 to 6 hours on this regimen. Controversial, but this is how I would treat myself or a family member with probable/presumed TASS.
Finally, if my wife or I were a known MRSA/MRSE carrier, what would I do or want done preoperatively, intraoperatively and postoperatively if cataract surgery were planned? We have some good antibiotics with minimal resistance available, namely Polytrim (polymyxin B sulfate and trimethoprim ophthalmic solution, Allergan), bacitracin ointment and compounded vancomycin. So, preoperatively, I would treat any culture positive nares with 2% Bactroban (mupirocin, GlaxoSmithKline) four times daily and put Polytrim drops in four times daily and bacitracin ophthalmic ointment at night for a week. At surgery, the usual good Betadine prep and careful draping. Intraoperatively, I would inject Tri-Moxi-Vanc (Imprimis) into the vitreous. I would seal the wound with ReSure from Ocular Therapeutix. I would educate the patient about the signs and symptoms of endophthalmitis and then treat postoperatively with the same antibiotic medications as preoperatively (usually with intravitreal Tri-Moxi or Tri-Moxi-Vanc, I do not use a postoperative antibiotic or steroid drop, only a topical NSAID). I would see the patient at 1 day, 1 week and 2 weeks after surgery. I would also do eye and lid hygiene with Avenova at least twice daily, which is soothing, good for treating blepharitis/meibomian gland dysfunction, and a good staph killer preoperatively and postoperatively.
I am hopeful that in 5 years we will have proven FDA-approved treatments for EKC. I suspect we will not for TASS and the MRSA/MRSE-positive preoperative patient. Such is the practice of medicine, as much art as science, and there are not always three or more well-designed prospective masked randomized clinical trials to guide us with so-called level 1 evidence. Many on our Cornea Health Round Table would have disagreed with one or even all of my positions. Open debate among experienced clinicians is how I best learn. Join us in 2015 at OSN New York for a great learning experience.
Disclosure: Lindstrom reports he is a consultant to Alcon, Bausch + Lomb, Imprimis, NovaBay and Ocular Therapeutix.