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Approach to the Management of Bullous Keratopathy Michael C. Chen, MD May 15, 2015 HM CF 1M Pain HM HM Pain HM HM Pain Infectious keratitis Purpose To give an overview of how to approach and manage bullous keratopathy Corneal Anatomy Wilson SA et al. Management of corneal abrasions. Am Fam Physician 2004;70:124. Endothelial Pump Hatton MP et al. Corneal edema in ocular hypotony. Exp Eye Res 2004;78:549. Corneal Anatomy Normal endothelial cell density at birth: > 3500 cells/mm2 Bourne WM et al. Specular microscopy of human corneal endothelium in vivo. Am J Ophth 1976;81:319-23. Pigatto JAT et al. Morphological analysis of the corneal endothelium in eyes of dogs using specular microscopy. Pesq. Vet Bras 2008;28;427-30. Endothelial Cell Loss Decreases with age Without surgery: 0.6% per year Bourne WM et al. Specular microscopy of human corneal endothelium in vivo. Am J Ophth 1976;81:319-23. Bourne WM et al. Central corneal endothelial cell changes over a ten-year period. IOVS 1997;38:779-82. Endothelial Cell Loss Without surgery: 0.6% per year With cataract surgery: Initial loss + 2.5% per year With corneal transplant: Initial loss + 4.2% per year Bourne WM et al Continued cell loss ten years after lens implantation. Ophthalmology 1994;101:1014-23 Ing JJ et al, Ten-year postoperative results of penetrating keratoplasty. Ophthalmology 1998;105:1855-65 Endothelial Loss: SICS Study ECD Loss Timepoint George et al. 4.21% 6 weeks Mathew et al. 7.67% 6 weeks Gogate et al. 15.3% 25.9% with PC rent 6 weeks Ganekal et al. 16.49% 6 weeks Jiang et al. 19.0% 1 month Ganekal S et al. Comparison of morphological and functional endothelial cell changes after cataract surgery: phacoemulsification versus manual small-incision cataract surgery. Mid E Afr J Ophth 2014;21:56-60. George R et al. Comparison of Endothelial cell loss and surgically induced astigmatism following conventional extracapsular cataract surgery, manual small-incision surgery and phacoemulsification Gogate P et al. Comparison of endothelial cell loss after cataract surgery: phacoemulsification versus manual small-incision cataract surgery. JCRS 2010;36;247-253. Jiang T et al. Cataract surgery in aged patients: phacoemulsification or small-incision extracapsular cataract surgery. Int J Ophth 2011;513-8. Mathew PT et al. Endothelial cell loss and central corneal thickness in patients with and without diabetes after manual small incision cataract surgery. Cornea 2011;30:424-8. Endothelial Cell Loss ECD threshold for corneal decompensation: ? ~ 500 to 700 cells/mm2 Endothelial Cell Loss ECD threshold for corneal decompensation: ? ~ 500 to 700 cells/mm2 Inadequate endothelium Stromal edema Subepithelial bullae Pain and decreased vision Treatment Options Non-Surgical Surgical Hypertonic saline Collagen Crosslinking Bandage contact lens Phototherapeutic keratectomy ? Honey Amniotic membrane Conjunctival Flap Corneal cautery Anterior stromal puncture Corneal transplantation Treatment Approach Step 1: Treat any underlying inflammation or increased IOP Avoid carbonic anhydrase inhibitors (i.e. dorzolamide, brinzolamide, acetazolamide) Things to Consider Clinical factors: Severity of edema Location of edema (stromal or epithelial) Visual potential Functional status of the contralateral eye Patient factors: Primary concern (pain or vision) Compliance and followup ability Finances 5% Hypertonic Saline Cornea osmotic pressure: 300 mOsm 5% hypertonic saline: 1500 mOsm Frequency of treatment: 4-8x/day Brubaker RF et al. Microcryoscopic determination of the osmolality of interstitial fluid in the living rabbit cornea. Invest Ophthal 1962;653-660 Stanley JA et al. In vivo determination of endothelial permeability to water. Invest Ophthal 1966;371-7. Early (stromal) vs. Late (stromal + epithelial) stages of disease Visual acuity and pachymetry improved only in Early group Effective in patients with central corneal thickness <694 microns Not effective in patients with bullae Knezovic et al, Therapeutic efficacy of 5% hypertonic solution in patients with bullous keratopathy, Coll Antropol 2006;30:405-8 Bandage Contact Lens Hydrophilic soft contact lens Addition of 5% hypertonic saline may be helpful May increase neovascularization ? Duration of leaving the contact in ? Prophylactic antibiotics Gasset AR et al. Bandage lenses in the treatment of bullous keratopathy. AJO 1971;72;376-80 Takahashi et al. Hydrophilic contact lenses in corneal disease. 3. Topical hypertonic saline therapy in bullous keratopathy. Arch Ophth 1971; 86: 133-7 http://www.issaquahvision.net/uploads/image/products/products_contactlenses_contact.jpg Honey Used by Egyptians as early as 5000 years ago Hyperosmotic Anti-inflammatory Anti-oxidative Mansour AM et al. Bullous keratopathy treated with honey. Acta Ophth Scand 2004;312-3. http://www.nectarcafenj.com/files/honey-kills-bacteria1.jpg 24 patient with bullous keratopathy 1 drop of raw honey 3-4x/day All patient had clearing of bullae Mean VA improved from CF50cm to CF2m ?Clostridium botulinum spores Mansour AM et al. Bullous keratopathy treated with honey. Acta Ophth Scand 2004;312-3. http://www.nectarcafenj.com/files/honey-kills-bacteria1.jpg Collagen Cross-linking (CXL) Application of topical riboflavin-A and ultraviolet-A light induces corneal stromal crosslinks and stiffens the tissue Crosslinking compacts the anterior stromal collagen fibers and decreases the hydration of the cornea www.lasik-sa.co.za Collagen Cross-linking (CXL) Within 1 month: Improvement in visual acuity Improvement in symptoms Decrease in central corneal thickness Regression observed over 3-6 months More effect on earlier stages of disease? Arora R et al. Role of corneal collagen cross-linking in pseudophakic bullou skeratopathy: a clinicaopathological study. Ophthalmology 2013;120:2413-8. Sharma N et al. Outcomes of corneal collagen crosslinking in pseudophakic bullous keratopathy. Cornea 2014; 33:243-6. Phototherapeutic Keratectomy Excimer laser (193 nm) ablation Removes abnormal basement membrane/stroma Promotes stronger adhesion between epithelium and stroma Lowers the osmotic load of the stroma Deeper treatments (100 microns) effective in relieving pain Promotion of scarring Ablation of nerve plexus Lin P et al. Combined phototherapeutic keratectomy and therapeutic contact lens for recurrent erosions in bullous keratopathy. BJO 2001;85:908-11. Maini R et al. A comparison of different depth ablations in the treatment of painful bullous keratopathy with phototherapeutic keratectomy. BJO 2001;85:912-5. Thomann U et al. Phototherapeutic keratectomy for bullous keratopathy. BJO 1995;79:335-8. http://www.institutmacularetina.com/wp-content/uploads/PRK.jpg Amniotic Membrane Use on eye first described in 1940, popularized in 1990s Harvested from innermost layer of human placenta Basement membrane is similar to that of conjunctiva Mechanisms: mechanical barrier scaffold for epithelial growth Dua HS et al. The amniotic membrane in ophthalmology. Suv Ophth 2004;49:51-77. Altiparmak UE et al. Prospective comparison of two suturing techniques of amniotic membrane transplantation for symptomatic bullous keratopathy. AJO 2009;147:442-06. At 6 months, no difference in symptoms between groups At least 80% of both groups had no pain Chawla B et al. Comparative evaluation of phototherapeutic keratectomy and amniotic membrane transplantation for management of symptomatic chronic bullous keratopathy. Cornea 2010:29:976-9.. Conjunctival Flap Popularized by Gundersen in 1958 Superior conjunctiva mobilized over cornea Alleviates pain by providing a mechanical barrier Gundersen T, Arch Ophth 1958;60:880-8. Indiana University http://eyeatlas.glick.iu.edu/photo.php?id=43 Gundersen T, Arch Ophth 1958;60:880-8. Conjunctival Flap Disadvantages: Cosmesis Flap retraction (10-15%) Shortened fornix Loss of ability to perform future glaucoma surgery Potential loss of limbal stem cells for future corneal transplant Corneal Cautery Debride loose epithelium Apply ~450 spots with electrocautery DeVoe. Electrocautery of Bowman’s membrane. Arch Ophth 1966;76;768-71 Anterior Stromal Puncture First described in 1986 for recurrent erosion syndrome Promotes stronger adhesion between epithelium and stroma Low cost and possible to perform at slit lamp Usually no progression of neovascularization Can be performed while waiting for a corneal transplant McLean EN et al. Recurrent erosion: treatment by anterior stromal puncture. Ophthalmology 1986;93:784-8. Cormier G et al. Anterior stromal punctures for bullous keratopathy. Arch Ophth 1996;114:654-8. Gomes JAP et al. Anterior stromal puncture in the treatment of bullous keratopathy. Cornea 2001;570-2. Sridhar MS et al. Anterior stromal puncture in bullous keratopathy. Cornea 2001;573-9. Anterior Stromal Puncture Anterior Stromal Puncture Video Preop 3 Weeks Postop At 6 months: Presence of bullae Presence of subepithelial fibrosis Complete absence of pain ASP (n=18) 37.5% AMT (n=20) 22.2% 100% 88.9% 75% 66.7% Paris FdS. Amniotic membrane transplantation versus anterior stromal puncture in bullous keratopathy.: a comparative study. BJO 2013;97:980-4 Corneal Transplantation Penetrating Keratoplasty (full thickness) Descemet’s Stripping Endothelial Keratoplasty (partial stroma/ DM/endothelium) Descemet’s Membrane Endothelial Keratoplasty (DM/endothelium) Tan et al. Corneal transplantation. Lancet 2010;379:1749-61 Penetrating Keratoplasty Full thickness transplant Long rehabilitation time/ Many followup visits Irregular astigmatism Suture related complications Risk of dehiscence with trauma Tan et al. Corneal transplantation. Lancet 2010;379:1749-61 Corneal Transplant Prognosis: By Diagnosis 10 year graft survival rate Keratoconus: Fuchs’ Dystrophy: Corneal scar (non-herpetic): Corneal scar (herpetic): Bullous keratopathy: Repeat corneal transplant: 89% 73% 70% 60% 42% 37% Williams K et al. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation 2008; 86: 1720–24. Endothelial Keratoplasty Tan et al. Corneal transplantation. Lancet 2010;379:1749-61 Endothelial Keratoplasty Video Endothelial Keratoplasty Video Endothelial Keratoplasty Increasing popularity since 2005 Preferred procedure for endothelial decompensation Coster DJ et al. A comparison of lamellar and penetrating keratoplasty outcomes. Ophthalmology 2014;121:979-87. Endothelial Keratoplasty Increasing popularity since 2005 Preferred procedure for endothelial decompensation Greenrod EB et al. Center and surgeon efect on outcomes of endothelial keratoplasty versus penetrating keratoplasty in the United Kingdom. AJO 2014;158:957-66.. Endothelial Keratoplasty Predictable refractive error; less irregular astigmatism No suture related complications Less risk of dehiscence ? Less risk of rejection ? Steep learning curve and higher risk of graft failure Take Home Points Management of bullous keratopathy is a challenge Respect the endothelium: prevention is key Consider clinical and patient factors in choosing treatment Thank you! [email protected]