Keratoconus and Its management

Keratoconus and its management

1. Ectatic disorder of Cornea “Keratoconus” Prepared by: Santosh C hhetri Master in Clinical Optometry (II Batch) Moderator: Dr. Rachana Singh

2. Introduction Cornea Ectasia Keratoconus Introduction Cascade Hypothesis Classification Management Take home message

3. “ Ectasia ” as defined in most medical dictionaries refers to a dilation or distention of a tubular structure. * “ Ectasia progression” is defined by a consistent change in at least 2 of the following parameters : 1. Steepening of the anterior corneal surface 2. Steepening of the posterior corneal surface 3. Thinning and/or an increase in the rate of corneal thickness change from the periphery to the thinnest point.” * Gomes JA, Rapuano CJ, Belin MW, Ambrósio Jr R. Global consensus on keratoconus diagnosis. Cornea. 2015 Dec 1;34(12):e38-9. Corneal Ectasia

4. As opposed to “thinning disorders” the following are classified under “ ectatic diseases ” Keratoconus PMD Keratoglobus Postrefractive surgery progressive corneal ectasia Gomes JA, Rapuano CJ, Belin MW, Ambrósio Jr R. Global consensus on keratoconus diagnosis. Cornea. 2015 Dec 1;34(12):e38-9

5. Keratoconus

6. Introduction Non-inflammatory, progressive thinning of the cornea that results in apical protrusion ( ectasia ) resulting in a high degree of irregular myopic astigmatism with observable structural changes appearing in later stages . The prevalence of keratoconus varies widely depending upon the geographic location and diagnostic criteria used * The reported incidence of keratoconus is 1 in 2000 individuals. * The reports of two surveys in the UK indicated a prevalence 4.4 and 7.5 times greater for Asian (Indian, Pakistani, and Bangladeshi) subjects compared with white subject.* Gokhale NS. Epidemiology of keratoconus . Indian journal of ophthalmology. 2013 Aug;61(8):382 Georgiou T, Funnell CL, Cassels -Brown A, O’Connor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic diseases in Asian and white patients. Eye ( Lond ) 2004;18:379–83 11. Pearson AR, Soneji B, Sarvananthan N, Sandforth -Smith JH. Does ethnic origin influence the incidence or severity of keratoconus ? Eye ( Lond )  2000;14:625–8 Rabinowitz YS. Keratoconus . Surv Ophthalmol 1998;42(4):297–319. Edwards M, McGhee CN, Dean S. The genetics of keratoconus . Clin Exp Ophthalmol 2001;29(6):345–51.

7. Keratoconus and ectatic corneal diseases have been recognized for more than 150 years . * Posterior corneal elevation abnormalities must be present to diagnose mild or subclinical keratoconus. * Krachmer JH, Feder RS, Belin MW. Keratoconus and related non inflflammatory corneal thinning disorders. Surv Ophthalmol . 1984;28: 293–322 . Rabinowitz YS. Keratoconus. Surv Ophthalmol . 1998;42:297–319 . Gomes JA, Rapuano CJ, Belin MW, Ambrósio Jr R. Global consensus on keratoconus diagnosis. Cornea. 2015 Dec 1;34(12):e38-9.

8. No gender predisposition More common in hot, dry climates Zadnik K, Barr JT, Edrington TB, et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci 1998;39(13):2537-46.

9. 1. Characterization of the abnormal matrix The keratoconus corneas had decreased levels of fibronectin , laminin , entactin , type IV collagen and type XII collagen associated with the epithelial basement membranes. There were also increased levels of fibrosis-associated extracellular matrices such as type III collagen, tenascin -C, and fibrillin-1 in the regions of anterior stromal scars and disrupted Bowman’s layer

10. 2.Enzyme and inhibitor abnormalities Keratoconus corneas had elevated levels of gelatinase activity. It is likely that keratoconus corneas have an imbalance between the corneal MMP-2 and its inhibitors, tissue inhibitors of metalloproteinases (TIMPs ) Keratoconus corneas have decreased levels of enzyme inhibitors and increased enzyme activities that can degrade the various extracellular matrices within the keratoconus corneas. The inhibitor–enzyme imbalance undoubtedly plays a major role in the stromal thinning and Bowman’s layer/basement membrane breaks that are characteristic of keratoconus corneas.

11. 3. Apoptosis in keratoconus corneas The keratoconus corneas have increased apoptosis and this phenomenon of cell death may be important in its pathogenesis . Factors that cause apoptosis include chronic epithelial cell damage, increased levels of LAR(of leukocyte common antigen related protein) and decreased levels of TIMP-1.

12. 4. Abnormal regulation and signal transduction Keratoconus corneas have increased levels of Sp1, a transcription factor that can down-regulate proteinase inhibitor. Phosphotyrosine phosphatase enzyme (LAR)(function of the phosphotyrosine phosphatase is removal of the phosphates from the tyrosine molecules) that was found in keratoconus but lacking in normal corneas

13. 5. Oxidative damage in keratoconus corneas Keratoconus corneas have increased oxidative damage compared to normal .They lack the necessary enzyme components (ALDH3, superoxide dismutase ) to process the reactive oxygen species that occur . With an accumulation of the reactive oxygen species , there is a resultant deposition of cytotoxic by-products ( malondialdehyde and peroxynitrites ) that can damage the corneal tissues.

14. Cascade Hypothesis – Oxidative Damage

15. Enzymes in lipid peroxidation &/or nitric oxide pathways are abnormal or defective ­Oxidative & cytotoxic by-products Various corneal proteins altered Cascade of events triggered: Apoptosis Signaling pathway altered ­↑ enzyme activities Fibrosis Cornea exhibits : Steepening ­↑ astigmatism ­↑ irregularity ¯ thickness Scarring Progressive changes After Kenney & Brown, 2003 Eventually, may show : Vogt’s striae Fleischer’s ring Ruptures in Descemet’s Hydrops Munson’s sign ­↑ nerve visibility Scissor retinoscopy reflex

16. Mechanical factors : Floppy eyelid syndrome ,eye rubbing associated with atopy or vernal keratoconjunctivitis Connective tissue disorders ( Marfan syndrome, Ehlers – Danlos syndrome ). Positive family history( The prevalence of keratoconus in first degree relatives is 3.34%, which is 15–67 times higher than the general population .) Down syndrome(0.5-15% of patients) Ethnic factors ( eg , Asian and Arabian )

17. Mild: <45 D Moderate: 45 – 52 D Advanced: 52 – 62 D Severe: > 62 D Booysen, 2003 KC: Classification by Corneal Curvature

18. Normal: 543 m Early: 506 m Moderate: 473 m Advanced: 446 m Classification by Corneal Thickness Booysen, 2003    

19. Nipple Oval Globus Morphological Classification Nipple Oval Globus

20. KC: Classification by Corneal Shape After: Bogan et al ., 1990, Rabinowitz et al ., 1996, Rasheed et al ., 1998, Levy et al ., 2004

21. Amsler Krumeich classification

22. Symptoms Asymptomatic Visual degradation reported Progresses slowly over first 5 – 10 years of life Ghosting/monocular diplopia due to irregular astigmatism Flare at night Photophobia Itching

23. External Sign Rizzuti Phenomena Munson’s Sign

24. Normal Mild Moderate Advanced Temporal Nasal

25. Signs ↓ unaided vision Scissoring Reflex Progression of myopia & Irregular astigmatism Distorted keratometry mires ↑ visibility of corneal nerve fibres Vogt’s striae Rupture of Descemet’s membrane (corneal hydrops ) Fleischer’s iron ring Corneal topography/Tomography

26. Early sign : Distorted retinoscopy reflex Irregular astigmatism ↓ unaided vision Marked changes in Rx sphere, cylinder, & axis Distorted keratometry mires Distorted photokeratoscope Placido rings Steepening in Topography/tomography Apical corneal thinning (stromal)

27. Later sign : Advanced cone formation seen in profile Apical scar formation Munson’s sign on lower lid Fleischer’s iron ring ↑ visibility of corneal nerve fibres Vogt’s striae Non-uniform red reflex with ophthalmoscopy Rupture of Descemet’s membrane (corneal hydrops ) ↓ IOP

28. Additional Sign in Advanced KCN Thinning Stromal edema Splits/tears in the endothelium/ Descemet’s membrane Endothelial cells may be elongated Corneal scarring

29. KISA%: Rabinowitz Criteria Corneal power (K) [>47.2 D] Inferior-Superior dioptric asymmetry (I-S) [>1.2 D] Sim K Astigmatism ( Ast ) >1.5 D Skewed Radial Axis (S RAX ) [>21°] If KISA% > 60%, case is a KC suspect KISA = (Central K) × (I−S) × (AST) × (SRAX) × 100/300

30. Management

31. Non surgical Management Verbal guidance to the patient regarding the importance of not rubbing eyes and use of topical lubricants (in case of ocular irritation) to decrease the impulse to rub eyes. U se of topical antiallergic medication( ie , antihistamines, mast cell stabilizer, antiinflammatory ) in patients with allergy. “Use of eye drops without preservatives is preferable in keratoconus patients.”

32. Does spectacle works in Keratoconus? Mild keratoconus in early stage can be corrected with spectacles. As the cornea steepens and becomes more irregular, glasses not capable of providing adequate visual improvement.

33. Soft contact lens Suited to early stage progression only as it does have any tear lens formation doesn't correct the irregularities. In cases of GP CL intolerance Usually, astigmatic component corrected with over-spectacles Contact Lens

34. RGP contact lens Eliminate corneal irregularities with pre-corneal tear lens formed by these lenses thus provides better visual correction

35. RGP fitting philosophies Apical clearance Apical bearing 3 point or divided support

36. APICAL CLEARANCE The central pooling or no apical touch and the bearing is towards the periphery Reduces the risk of scarring Tightening at the periphery may result in sealing the tear exchange

37. APICAL BEARING The central bearing or apical touch and the pooling is towards the periphery resulting in good visual acuity Results in the corneal scarring and intolerance

38. 3 POINT or DIVIDED SUPPORT Divided support or three point touch • An apical contact area of two to three millimetres, a intermediate clearance zone and mid peripheral contact annulus with conventional edge clearance at the periphery. CL weight distributed over larger area. Woodward EG. Contact lenses in abnormal ocular conditions— keratoconus . In: Phillips AJ, Speedwell L, eds.

39. So, what if patient cannot tolerate RGP lenses ?? Piggy back system Hybrid lens system

40. Piggyback CLs  Rigid lens fitted over a hydrogel lens increases comfort resulting in adequate wearing time with good vision SCL acts as a ‘carrier’ for the overlying GP CL Used to ↑ comfort & ↓ risk of epithelial abrasion by a GP CL Ultra-thin SCL (usually disposable )

41. Potential problems Piggyback CLs ???? Handling and care of two different types of lenses. Difficulty in obtaining centration of the rigid lens.

42. Better options than Piggy back ! One way to overcome the problems with piggy-back lenses, yet have the optics of a rigid lens with the comfort of a hydrogel, is to fuse a soft rim onto a hard central portion Hybrid Lens system

43. C ombine the benefits of rigid lens optics, including better lens centration and decreased aberrations, along with the comfort of a soft lens Potential C omplications … F lexure of the GP centre lens (leading to astigmatism and decreasing visual results), D ifficulties with insertion and removal of the lenses, and T earing at the GP lens and hydrogel skirt junction.

44.   Fully keratoconic designed lenses?? Scleral lens Rose k family of lens

45. Scleral Lens   Cornea is completely vaulted Creating an equal and opposite keratoconic surface ultimately restoring uniform optical lens and elimination of astigmatism. This result in less ghosting and much crisper vision Mini-Scleral – 12.5mm to 14.5mm Medium Range Scleral– 15.0mm to 18.0mm Full Scleral – 18.5mm to 28.0mm

46. Advantages Better comfort, Less mechanical trauma to the cornea better vision.

47. Rose K lens Unlike traditional contact lenses, the complex geometry built into every ROSE K contact lens closely mimics the cone-like shape of the cornea for every stage of the condition . The result is a more comfortable fitting lens for patients and better sight (visual acuity ). Standard lens designs with fixed optical zones (OZ) do not ideally fit the cone shape of keratoconus patients

48. Keratoconus show high flattening between the very steep apex of the cone and the flat periphery. Need to have very steep lenses in the center that get flatter quickly at periphery.

49. Fig shows a standard lens that will yield unwanted pooling at the base of the cone and peripheral bearing that can seal off and cause corneal problems

50. Fig demonstrates the benefits of a smaller optical zone to fit the cone contour. The design results in little tear pooling at the base of the cone and shows an even distribution of tears under the lens.

51. Key points: Use UV protection in the contact lenses and glasses Improve patient comfort in order to minimize eye rubbing Non-steroidal anti-inflammatory medications (NSAIDs) Preservative-free artificial tears Allergy medications Use properly fit contact lenses Contact and scleral lenses are extremely important for visual rehab. in patients with keratoconus .

52. Surgical Management C orneal cross-linking Deep anterior lamellar keratoplasty (DALK) Penetrating keratoplasy (PK)

53. Corneal collagen cross-linking (CXL) First described in 1998 by Spoerl et al. as a modality for increasing the corneal biomechanical strength to halt disease progression First data presented in 2003 by Wollensak et al . In April 2016 , the U.S. FDA gave approval to corneal collagen cross-linking to treat progressive keratoconus and post-LASIK ectasia . Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66:97–103 G.Wollensak , E. Spoerl , and T. Seiler, “Riboflavin/ultraviolet- ainduced ollagen crosslinking for the treatment of keratoconus ,” The American Journal of Ophthalmology, vol. 135, no. 5, pp. 620– 627,

54. Corneal collagen cross-linking (CXL) In CXL, riboflavin (vitamin B2) is administered in conjunction with ultraviolet A (UVA, 365 nm). –The interaction of riboflavin and UVA leads to the formation of reactive oxygen species, which leads to the formation of additional covalent bonds between collagen molecules, with consequent biomechanical stiffening of the cornea

55. Surgical Management Young ( eg , 15-year-old) patient with progressive KCN with satisfactory vision with glasses Perform CXL and prescribe glasses or contact lenses Older ( eg , 55-year-old) patient with stable KCN with satisfactory vision with glasses Prescribe glasses only or with contact lenses

56. Patient with stable severe KCN with unsatisfactory vision with glasses and contact and scleral lenses? This patient has moderate anterior corneal scarring but no evidence of previous corneal hydrops Perform DALK Patient with stable severe KCN with unsatisfactory vision with glasses and contact and scleral lenses? This patient has moderate anterior and deep corneal scarring with evidence of previous corneal hydrops PK alone

57. As for PK, the most important factor in considering keratoplasty in keratoconus is when Significant corneal scarring ( eg , posthydrops ) is present. C ontact lens intolerant or is not keen on wearing contact lenses; other surgical strategies fail, or are contraindicated; the cornea is very thin (200 um ); and K eratoconus is deemed to be severe and at a potential risk of acute hydrops .

58. TAKE HOME MESSAGE A proper assessment of corneal topography is required Careful Skilled fluorescein-pattern interpretation is the cornerstone of successful CL fitting

59. Thank you Avoid eye rubbing to avoid KCN progression……..