How to Mend a Broken Cornea

1. How to Mend a Broken Cornea EyeMed 2019 Brian P. Den Beste, OD,FAAO Kyle Den Beste, MD

2. The Ayes, Eyes, I’s have it. • INFLAMMATION • INFECTION • INJURY

3. Corneal Anatomy • Three layers : Epithelium, Stroma , Endothelium. • 50-60 microns thick, • Epithelium: Superficial defects, Irregular configuration, able to regenerate to fill in defects like ulcers • Sometimes needs to be scraped to reform and come back more adhered to Bowmans • Sometimes just not optically happy and needs to removed to grow back “ Mo Clear”

4. Corneal epith • PEK punctate epith keratitis, small areas of inflammation …grey • PEE punctate epith erosions • SPK Thygeson's coarse epith change • When epithelial cells slide from the limbus and wing cells. It can come from the conjunctiva but these are not optically good • Limbal transplants for chemical burns

5. Stroma • When its gone its gone • DLK : white blood cells flow via the path of least resistance • You loose stroma and your going to have a divot…divots result in irregularity and this creates more prominent obscuration than an opacity …in the cornea… RGP ,not PTK is more often the answer

6. Endothelium • Low cell count and the pump is unable to keep the stroma clear • Trauma during cataract surgery ( phaco power) will lower the cell count. • Viscoat is the endo’s best friend • Femto might be the second best friend • Shallow AC is your worst enemy ie hyperopes and small eyes

7. Endothelium cont • Its attached to Descemet’s membrane • Sometimes detaches during cataract surgery • DSEK vs DMEK • No longer necessary to transplant the entire cornea when the problem is the pump

9. Corneal Inflammation • NO blood vessels….typically • The conjunctiva and limb us are loaded with soldiers ready to attack whatever is going on in the cornea…sometimes even when the “war is over” • They attach by sending in WBCs or grow vessels to get the pipeline even closer • Analogous to lung tissue. Your head cold and the virus are gone but you keep coughing.

10. Diagnosis • Sometimes difficult because EACH etiology, typically is accompanied with inflammation • Why is inflammation such a big part of corneal disease?

11. Treatment options • Anti infective agents • Antibiotics • Antivirals • Antimycotics • Anti inflammatory agents: steroids • Both • Neither • Lube and/or cover • Surgery : limbal tissue transplant, tarsorrhaphy, Glue, Graft /patch graft, reposition descemets or stromal flap

12. Steroids • Best friend or worse enemy • Hard to imagine treating corneal disease without them • Probably the biggest problem, however when dealing with infection and particularly fungal infection. The bug keeps growing but you can’t tell because the inflammatory response is muted. • Similar with bacterial ulcers

13. I’s have it: #1. Inflammation • Contact related: CLARE, metabolic keratoconjuntivitis • Rosacea and posterior blepharitis • DLK…diffuse lamellar keratoconjunctivitis • Mooren’s ulcer • Disciform HSK • Infectious ulcers that won’t re-epithelialize

14. I’s: #2 Infection • Herpes Simplex Keratitis • Herpes Zoster Keratitis • Adenoviral keratitis EKC • Bacterial Ulcer • Fungal or mycotic ulcer • Amoeba

15. I’s: #3 Injury • Abrasion/ Recurrent corneal erosion • Penetrating corneal injury or laceration • Iatrogenic: Wound leaks, Descemet’s detach • Penetrating keratoplasty, DSEK, DMEK, DALK for endothelial and stromal disease • Chemical keratitis • Medicamentosa: Glaucoma meds

16. I’s: #3 Injury cont. • Exposure Keratitis • Nocturnal Lag ophthalmous • Floppy Eyelid syndrome • Dellen from filtering sx or pterygium • 7th Nerve palsy from Bell’s palsy or SX • Ectropian or Entropian • Thyroid eye disease • Fishing Mucous syndrome

17. #1 Inflammation- CLARE • Contact lens associated red eye • Some think its related to bacteria but most think it’s hypoxia • Is it more common with silicone hydrogels? • Definitely more of an issue with EW • Probably more with torics….and hyperopic • ? Colored cls. • Can be related to solutions…hydrogen peroxide with platinum neutralizing disc

18. Wrong bottle

19. When hydrogen peroxide not neutralized

20. Wrong bottle.

21. Clare • Sometimes with large areas of epithelial erosion. Like paint splintering off the wall • Sometimes associated with peripheral infiltrates and sometimes with infiltrates that are not so peripheral • The closer to fixation the more problematic

22. Clare and Infiltrates • Do they stain? • Are there multiples? • Do they have concomitant facial inflammation… fair skin, rosacea, blue eyes? • Is there anterior chamber reaction • It is usually unilateral

23. Clare and Infiltrates • The eye is confused …sending in warriors without an infection • Pinpoint lesion? • Pupil is a good gauge for sizing • Tx : remove lens • IF lens has been off for > 12 hrs and they are still staining lubricate or reassure and see back the next day, if feeling better then start steroids….to turn down the volume

24. Infiltrates • Most Drs start them on tobradex or blephamide or maxitrol • Smarter to wait a day and use steroids, can’t increase combo gtts if need more anti-inflammation….then get too much ATB and more potential for toxicity • Cost is a consideration • Change the SCL regimen.. EW to DW… • DW to daily disp, ? Really need a toric.

25. Non silicone? • Silicone hydrogels stiffer but more permeability, more deposits? but….less comfort? • Acuvue 2 no longer made • Proclear is a non silicone option

26. Rosacea / posterior blepharitis • Number one misdiagnosed keratoconjunctivitis • Is often an underlying issue that makes another problem bad • Eyes get red when I wear scls • Had a small erosion after my cataract surgery but now I have constant foreign body sensation

27. Rosacea • Common denominator for slow healing • Negative lottery : rosacea, anterior basement membrane dystrophy and cataract surgery • “Don’t rub your eye” .. .compounds the issue • Similar : Lasik patient , pretty blue green eyes, deposit builder with scls, facial fairness/ mild rosacea, “ don’t rub your eyes” Formula for disaster

28. Rosacea • IF peripheral infiltrates, need topical steroids • Lid massage….Lipiflow works too • PO meds in low dosage • ? Restasis • No Punctal plugs • Reassurance

29. Rosacea cont • Spectrum of disease • Mild to corneal vascularity, thinning and perforation • Patient was treated for bilateral HSK by a corneal specialist

30. Dry Eye • Severe rheumatologic patients with sjogrens syndrome • Often with filaments • Try punctal plugs for neurotrophic cases, short term BCL • Topical steroids • Sometimes autologous gtts ( made from patients serum) • Sometimes acetyl cysteine gtts 5% (mucomyst)

31. Mooren’s ulcer • Inflammation usually in the form of an infiltrate often paralleling the limbus in a non contact lens wearer…they are sterile ulcers • They can have stromal thinning quickly • WBCs devouring normal tissue: polymorphonuclear • Case of “EKC” 30 yr BF that worsened and then had micro perforation inside of week • Claimed she was “healthy” • Told her to see her family dr. and she was hospitalized…unconscious for several days

32. Mooren’s ulcer • 62 yr old WF, with long standing dry eye. • H/O Sjogren's disease • Intermittently referred in for bouts of filamentary keratitis • Last episode, inferior infiltrate despite steroids, BCL, lubrication, Prokera, autologous gtts x 4 months • Finally referred back to her rheumatologist

33. Mooren’s ulcer • She was placed on an older Dmard: Plaquenil 200 mg and inside of a wk. her symptoms resolved. This was after 4 months of torture • disease-modifying antirheumatic drugs (DMARDs). • Biologics: Humara, Enbrel, Orencia

34. Diffuse Lamellar Keratitis • An inflammatory response to foreign matter in the interface • Anytime there is an inflammatory event : iritis , corneal FB, Hzo, you can get DLK • It is the path of least resistance for the soldiers to flow through

35. DLK • See it day one • It is rare but can cause permanent visual changes • Increase steroids topically, add po steroids, refloat and irrigate…..step by step process unless florid DLK • Avoid with irrigation during repositioning of flap

36. Disciform HSK • Stromal inflammation without epithelial disease • Usually not an initial episode • Thought to be an immunologic response • Tx ; with steroids and anti virals • Usually PO meds as well

37. I’s #2 Infection • Microbial keratitis • Fungal keratitis • Parasite keratitis • Viral Keratitis • HSK • HZO • EKC

38. Microbial Keratitis • Corneal Disease remains the leading cause of monocular blindness worldwide. • Update on the Management of Infectious Keratitis. Ophthalmology: 2017: 124:1678-1689 • Diagnosis is key. Culture still the std…great if you have a relationship with lab. Slides give quick idea if G+ or G`. Culture can be 24 hrs or longer if fungus ( 72 hrs at earliest) • In vivo confocal microscopy helpful with fungus and Acanthamoeba.

39. Microbes cont • Topical antibiotic remain the best tx for bacterial ulcers and “ a recent review found all commonly rx’d ATB were equally affective. • Comfort and toxicity less with mono-therapy

40. 1996 !! • Ophthalmology. 1996 Nov;103(11):1854-62; discussion 1862-3. • Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group. • CONCLUSION: • Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

41. Gatifloxacin 0.3% Versus Fortified Tobramycin–Cefazolin in Treating Nonperforated Bacterial Corneal Ulcers: Randomized, Controlled Trial Sharma, Namrata MD, MNAMS*; Arora, Tarun MD, DNB, FICO*; Jain, Vikas MD*; Agarwal, Tushar MD*; Jain, Rajat MS*; Jain, Vaibhav MD*; Yadav, ChanderPrakash PhD†; Titiyal, Jeewan MD*; Satpathy, Gita MD‡ Cornea: January 2016 - Volume 35 - Issue 1 - p 56–61 Conclusions: Using the prespecified definition of equivalence of ±20%, this trial found evidence that gatifloxacinmonotherapywas equivalent to combination therapy with cefazolin and tobramycin for the treatment of nonperforated bacterial corneal ulcers.

42. Managing nonresponsive bacterial keratitis cases. Dr. Edward Alfonso. Ophtho times sept 2017 • Pseudomonas accounted for the bulk of bacterial isolates. Staph aureus a distant second • The biggest reason a bacteria didn’t respond to treatment was because it was a fungus and not a bacteria. • 80 % of cases are treated empirically without any microbiologic studies. Drs. see SCL assoc. ulcer and mucopurulent discharge and assume pseudomonas

43. Anticollagenases • During acute phase of infection fibroblasts, keratocytes and other inflam cells secrete enzymes: collagenases …stabilization may make corneal melting less • No good studies to guide clinicians on the use of doxycycline for the tx of corneal ulcers despite wide spread use. • Rabbit studies show some impressive outcomes.

44. SCUT trial • Steroids for Corneal Ulcers Trial: SCUT • Srinavasan M, et al • RESULTS: • Screen 1769 N= 500 • No significant difference • was observed in the 3- • month BSCVA, • infiltrate/scar size, time to • re-epithelialization or • corneal perforation • CONCLUSION • We found no overall • difference in 3-month • BSCVA and no safety • concerns with adjunctive • corticosteroid therapy for • bacterial corneal ulcer

45. Non healing ulcers • Not a big lover of steroids and antibiotics on microbial keratitis but sometimes after the ulcer is sterile you can’t get reepithelialization until steroid is added. • Amazing how comfortable they are but still have epi defect • I am slow to add the steroid

46. Infection cont. • Fungal ulcers often have worse outcomes than bacterial with no new tx since the 1960s when Natamycin was introduced • I think mycotic ulcers often are misdiagnosed for many wks and thus the bad label • Patients with scls and /or on immuno-suppressives or DMARDs are at risk

47. MUTT IMycotic ulcer treatment trial • Showed a benefit of Natamycin over voriconazole particularly in fusarium infections • MUTT II : showed little help from rxing po voriconazole and since there are potential systemic issues with the po meds. But should be considered if treating fusarium

48. Herpes Simplex • Affects 500,000 people in the US. • It is the number one cause of unilateral infectious corneal blindness in developed countries. • Different from bacterial and fungal ….can be recurrent.

49. Treating HSK • Trifluridine still number one • Topical Acyclovir is the most common tx in Europe but not avail in US • Gancyclovir ( Zirgan) is used for HSK, and is being use for Varicella zoster keratitis as well as the rare CMV keratitis • Large randomized study ongoing looking at effectiveness or Zirgan for VZK…trifluridine is not indicated

50. HEDS I • Herpetic eye disease study • Evaluated the effectiveness of using steroids in HSV stromal keratitis. • Showed drastic improvement in the steroid treated group • Also studies the use of oral acyclovir ( 200 mg 5 times a day) . Not as statistically significant of a result. Hard to determine if one group was better and they all had stromal disease , not epithelial keratitis