Recurrent corneal erosions and ptk

Recurrent corneal erosions
yy Dr.Haridas

1. Recurrent corneal erosions and PTK Dr.Haridas

2. Brief History This clinical entity was first described by HANSEN in the year 1872 and he named it “intermittent neuralgic vesicular keratitis” the term recurrent corneal erosions was coined by Von Artl in 1874 Both recognized antecedent trauma Vogt in 1921 described fine white dots on Bowman’s layer , fluorescein staining lines , and an irregular epithelial surface with localized odema using slit lamp

3. Chandler classified recurrent corneal erosions into 2 main forms Chandler’s microform erosions in which minor episodes which usually last from few minutes to hours and show no obvious epithelial defect Chandler’s macroform erosions are severe episodes may persist over several days and associated with intolerable pain decreased vision and photophobia , a frank epithelial defect in slit lamp examination

4. Recurrent erosions of the corneal epithelium is a clinical syndrome of multiple etiologies , characterized by inadequate epithelial-stromal attachments, resulting in episodic dys - adhesions and defects of the corneal epithelium The condition occurs across all ages , however the average age is the mid-fifth decade with a slight female predominance

5. The corneal epithelium is firmly adherent to underlying Bowman layer and stroma by specialized attachment complexes c omprised of hemidesmosomes of the basal cells Cell adhesion molecules – integrin Anchoring fibrils of type VII collagen secreted by basal cells

6. The long cliliary nerves provide the perilimbal nerve ring Fibres penetrate the cornea in deep peripheral stroma and Lose their myelin sheath within a short distance into the cornea and run parallel to epithelium Turn toward the surface penetrating the Bowman’s layer and basement membrane forming sub basal plexus and finally terminate in the wing cells as nerve endings

7. pathogenesis The changes which reduce the adhesion of the corneal epithelium include a deficient basement membrane The absence and abnormality of hemidesmosomes Loss of anchoring fibrils Increased level or activity of several members of matrix metalloproteinase (MMP) including MMP-2 , MMP-9 are reported in patients having RCE

8. S ymptoms Repeated episodes of sudden onset of pain usually at night or upon first awakening accompanied by redness photophobia and watering of the eyes

9. Primary a) Epithelial basement membrane dystrophy b) Dystophy involving Bowman’s layer -Reis-Buckler’s dystrophy -Thiel- Benke dystrophy c)Stromal Dystophy Lattice, Macular and Granular dystrophies d)Endothelial dystrophy Etiologies of Recurrent C orneal E rosions

10. II. Secondary a) Degeneration Band Keratopathy , Salzmann’s Nodular degeneration b) Trauma Epithelial abrasions , Chemical and thermal injury c) Eyelid pathology Entropion , ectropion , lagophthalmos , Meibomian gland dysfunctions, blepharitis d) Following Ocular Infections- Bacterial and viral keratitis e) Following Refractive surgery- LASIK,PRK f) Systemic causes Diabetes mellitus, epidermolysis bullosa , juvenile x-linked Alport’s syn g) Miscellaneous Keratoconunctivitis sicca , Bullous Keratopathy , idiopathic,

11. Trauma accounts for 45-69 % of cases Epithelial basement membrane dystrophy accounts for 20-30 % of cases Other dystrophic and degenerative diseases account for a minority of cases

12. Trauma leading to RCE Incidence estimates of RCE following traumatic corneal abrasions have ranged from 5 % - 25 % Corneal wound healing occurs in 3 phases Epithelial migration Epithelial proliferation Epithelial adhesion

13. Epithelial migration ~3hrs - Neutrophil accumulation (from tear film) occurs along wound edge and thinning of epithelium to a single layer of flattened cells Latent phase (4-6hrs) – characterized by increased intracellular protein synthesis, actin filament polymerization and reorganization from apical to basal region of cells Linear phase (4- 5 days) – the flattened cells move across the defect as a sheet until completely covered Lamellopodia & filopodia marks the beginning of cell migration

14. Epithelial Proliferation Basal epithelial cells are the key participants The transient amplifying basal cells reproduce via mitosis and the new cells move inwards toward the center of the defect, then upwards to fill it Stem cells at the limbus are responsible for the epithelial cell replacement by their increased mitosis EGF,TGF β and  and NGF plays a vital role

15. Epithelial Adhesion Reformation of the adhesion complexes occur gradually starting from periphery to centre Focal contacts at the leading edge of epithelium form by linkages from cytoplasmic actin filament to extracellular matrix proteins like fibronectin , laminin . Trauma predispose to RCE either because the basal epithelial cells fail to produce proper basement membrane complexes to attach to the Bowman layer or because of defective epithelial adhesion

16. Epithelial basement Membrane Dystrophy (EBMD) Cogan’s Microcystic (Map Dot Fingerprint) Dystrophy pathophysiologic hallmark is an abnormality in the formation and maintenance of the epithelial basement membrane adhesion complex of the corneal epithelium a history of recurrent erosions should suggest this diagnosis, especially if they are bilateral and occur in multiple sites

17. pathogenesis Epithellial cells produce abnormal multilaminar basement membrane , both in normal location and intra- epithelially Blocks the normal migration of epithelial cells toward the surface Trapped epithelial cells degenerate to form intraepithelial microcysts , which slowly migrate to the surface

18. With continued cycles of epithelial breakdown and aborted efforts at the development of a stable epithelial basement membrane adhesion complex, morphological changes eventually develop, which lead to the classic "map-dot-fingerprint" epithelial and subepithelial findings .

19. Map changes Dot changes

20. Inadequate formation of hemidesmosomes by the basal epithelial cells results in compensatory aberrant regeneration and duplication of the epithelial basement membrane, a change that is clinically manifested by the "fingerprint" lines. Fingerprint like changes

21. Diagnosis of RCE A history of prior corneal abrasions , especially a shearing injury as from a tree branch or a fingernail scratch can often be elicited In patients lacking a cause for erosions , examination done under fluorescein staining and retroillumination for EBMD in asymptomatic eyes

22. Adhesion test In cases where a erosion is suspected but lacks the evidence of epithelial defect in slit lamp examination , the presence of an occult epithelial adhesion is detected by use of dry cellulose surgical sponge rubbed gently and tangentially over the suspected area after topically anesthetizing the cornea. If the intact epithelial sheet is moveable ( + ve adhesion test) then the lack of adequate epithelial stromal adhesion is certain.

23. Management Conservative management aims mainly in resolution of the epithelial defect A)For relatively small (less than 1 quadrant of cornea) and clean (without infiltrate) defect 1) Lubrication This is considered first-line therapy frequent application of preservative-free artificial tears combined with 2) mild antibiotic eye ointment at bedtime (or more frequently) to prevent the eyelid from adhering to the corneal epithelium and antibiotic prophylaxis.

24. Topical immunomodulators such as 0.05% cyclosporine-A ( Restasis ), reduce the likelihood of RCEs by improving the lacrimal and mucin tear layer quality by inhibiting lacrimal gland T-lymphocyte proliferation and increasing goblet cell numbers, which can help decrease corneal friction.

25. Hypertonic (5%) sodium chloride drops will promote the epithelial adherence by increasing the the tear osmolarity , thereby decreasing the epithelial odema and promoting epithelial adherence. These agents should be continued for a few months as it takes few months for the adhesion complexes to build up

26. B) If the epithelial defect is larger and patient is extremely uncomfortable then continuous pressure patching (24-72hrs) is employed . C) In the presence of corneal stromal infiltrate and/or anterior chamber reaction , a concomitant infection must be suspected thereby microbiological cultures are performed

27. Therapeutic Contact lens provide symptomatic relief and encourage healing of the epithelium by protecting them from the ‘windshield wiper’ debridement action of the blinking eyelids Diadvantages – increase the risk of microbial keratitis hence a topical antibiotic( flouroquinolones ) should be used once/twice daily

28. a relatively flat (base curve >8.6mm), plano or low minus power , high water content SCL are preferred The lens can be worn from few weeks to several months, replacing it every 2 weeks

29. Any signs of underlying blepharitis should be treated with lid hygiene measures (hot compresses and eyelid scrubbing) with additional oral doxycycline in more severe cases. Combination therapy with topical lubrication, oral tetracyclines , and a topical corticosteroid particularly for patients with meibomian gland dysfunction Both doxycycline and methylprednisolone inhibit matrix metalloproteinase-9, which is implicated in cleaving scaffolding proteins in the corneal epithelial basement membrane. This inhibition can aid the recovery and reattachment of the corneal epithelium following RCE.

30. Punctal occlusion For chronic dry eye patients whose RCE is resistant to lubrication, punctal occlusion may be performed. This simple, one-time intervention can promote more rapid healing and prevent further attacks by increasing the ocular surface residence time of both natural and exogenously applied tears. As a trial, especially in patients with mild to moderate dry eye, a dissolvable short-term collagen punctal plug may be used . However, in patients with severe tear film insufficiency, longer-term silicone punctal plugs are recommended.

31. Autologous serum biochemical properties of blood serum are very similar to that of the tear film. It is composed of substances necessary for epithelial healing, such as vit A , EGF,TGF β and fibronectin. The lipids present in serum acts as a substitute for lipid components produced by meibomian glands Autologous serum generally is accepted as safe Disadvantages - costly and cumbersome

32. Amniotic membrane (AM) patching Transplantation of cryo -preserved AM exerts anti- inflammatory, anti-scarring and anti- angiogenic actions , they contain tissue inhibitors of MMPs Under topical anesthesia, debridement of the loose epithelial cells by a dry cellulose sponge is done and the corneal surface is covered with AM They act as a biological bandage and help in treating RCE

33. hydrated amniotic tissue PROKERA (Bio-Tissue , Inc , Miami FL) has been approved by the FDA as a self retained sutureless medical device to promote corneal wound healing This device is an amniotic membrane sheet supported on a 16mm plastic ring. It can be applied simply as a large-diameter contact lens, though the ring itself is much thicker than a standard contact lens.

34. Surgical techniques Debridement Superficial epithelial keratectomy Anterior stromal puncture Phototherapeutic Keratectomy

35. Debridement Applied in cases with Extensive epithelial deterioration and residual associated cellular debris Mechanical debridement of loosely adhered or nonadherent epithelium provides a smooth basement membrane to which healthy epithelium may re-adhere This technique requires only a cotton swab or blunt instrument and can be performed at the slit lamp with topical anesthesia.

36. Devitalised epithelium and debris adherent to the damaged basement membrane surface inhibit restoration of intact basement membrane and recovery of tight epithelial- stromal adhesion

37. After the application of topical anesthetic, a gentle scrub with a dry cellulose sponge or No 15 BP blade is performed to sweep aside nonadherent epithelium and debris.

38. Jeweler’s forceps are employed to remove loose shards of marginal epithelium.

39. The surface of the Bowman’s layer is polished with a dry cellulose sponge . Topical antibiotic are applied followed by pressure patch. If the defect persist >72hrs, then patch is replaced with BCL

40. limitations of this procedure derive from the fact that no significant modifications to enhance epithelial adhesion are made in Bowman’s layer or other deeper corneal structures

41. Superficial keratectomy The optimum candidate for this procedure has spontaneous multiple erosions in different areas of the cornea, no history of trauma and severe basement membrane dystrophy , involving visual axis resulting in poor vision and large areas of loosely adherent irregular epithelium . The premise behind superficial keratectomy is that if irregularities in the epithelium and anchoring complex are removed and allowed to grow back in a controlled environment, the structures may normalize as they develop

42. Under local anesthesia (or, in some highly cooperative patients, the use of topical anesthetic agents) a lid speculum is inserted to hold the eye open. The area appropriate for debridement is identified with fluorescein or adhesion test . The epithelial and subepithellial debris are removed using dry cellulose sponge

43. A superficial plane of dissection using a No 15 BP blade is established in the perilimbal area Leaving approximately 1 mm of intact perilimbal epithelium, the rest of the epithelium and its basement membrane, if possible, are lifted and dissected free. An attempt should be made to peel and dissect away the epithelium in a continuous sheet.

44. Persistent epithelial fragments may be visualized by instilling fluorescein. Bowman’s layer should not be incised but should be scraped with a blade oriented perpendicular to the surface of the cornea, taking care not to produce linear scars in Bowman’s layer. Alternatively a diamond burr may be used to gently polish Bowman’s layer to enhance epithelial adhesion it leaves a smooth surface upon which new epithelium can grow

45. Anterior stromal puncture (epithelial reinforcement, corneal micropuncture ) This technique involved the use of a straight 20-gauge needle to make multiple shallow penetrations through the epithelium into anterior corneal stroma to improve epithelial adhesion, apparently by inciting focal microcicatrization to ‘spot weld’ the epithelium to stroma . This technique performed under topical anesthesia under slit lamp , and is best suited for those with single erosive areas(from trauma) in area outside the visual axis

46. A careful preoperative slit lamp examination should also include retroillumination . Epithelial reinforcement may be performed either between erosive episodes or through loose, irregular epithelium during an active erosion without the need for debridement. Topical nonsteroidal drops should be instilled every 10 to 15 minutes, starting 30 minutes to 1 hour before the procedure to aid in postoperative pain management. Also, several drops of a fluoroquinolone , or other broad- spectrum antibiotic drop used pre operatively.

47. The large gauge needle used to eliminate the risk of perforation , alternatively bending the tip of the needle like cystatome also helps in producing small punctures of consistent depth. The treatment is performed directly over the areas of defective epithelium or over the dysadhesive areas of cell sheet and should extend 1-2 mm beyond the erosive focus into normal tissue

48. Flouresein along with anesthetic , should be applied to help visualize the puncture marks.

49. Anterior stromal puncture also done using Nd Yag laser Advantages include minute and uniform wound with less corneal scarring, so the procedure can be repeated whenever necessary

50. Phototherapeutic Keratectomy The excimer laser revolutionized corneal refractive surgery in the 1990s. PTK was approved by the FDA in 1995. The ablation method involves 193nm laser emission with repetition rate upto 50hz and diameter 6.5mm. No more than 4 shots should be performed on one area in order to preserve the Bowman’s layer

51. FDA approved Indications of PTK Superficial corneal dystrophies (including granular, lattice and Reis Buckler’s dystrophy) EBMD and irregular corneal surfaces Corneal scars and Opacities

52. Ideal Patient criteria Significant visual compromise Pathological condition in anterior third of cornea Elevated or flat opacity Myopic Under consideration for corneal transplant Quiet, uninflamed eye Recurrent corneal erosion that has failed medical therapy

53. Pre operative evaluation Should be performed no longer than 90 days before the surgery Medical history (collagen vascular d/s , immunodeficiencies ) Visual acuity with and without correction Intraocular pressures Slit lamp examination Dilated fundus examination Irregular astigmatism should be evaluated by keratometry and corneal topography Preoperative corneal thickness is measured by pachymetry Anterior segment OCT used to have detailed view of entire cornea

54. Relative contraindications Pathological condition deeper than 1/3 rd of cornea Thin preoperative cornea Active ocular inflammation like uveitis Hyperopic refractive error Severe Blepharitis Lagophthalmos or poorly controlled dry eye Collagen vascular disease like RA Immunosuppression

55. Technique General Remove the bulk of opacity from the central cornea Smooth the central and mid peripheral cornea Remove the least amount of stroma that is required Ablate and check frequently during the procedure to ensure that only required amount of tissue is removed If the epithelium is helping create a smooth corneal surface , it is best to perform transepithelial ablation If the epithelium is exacerbating the corneal irregularity , it is mechanically removed before the laser treatment Masking agents are very helpful in smoothening the cornea

56. For recurrent corneal erosions All the loose epithelium is removed with a sharp blade A 6.5mm diameter circular PTK ablation is applied centrally for a depth of 5-6 µm , which is part way through the bowmans membrane If an area larger than the largest ablation zone needs to be treated , then the central area is treated and a 6.5 mm sponge is placed centrally to block the previously treated area, the laser ablation zone diameter is set to 4mm and peripheral areas are treated with barely overlapping 5-6 µm depth ablation

57. Masking agents These are substances that are applied to the cornea during the treatment to selectively block laser ablation to create smoother surface Saline or artificial tears are used the masking agents are applied in areas where no laser ablation is desired

58. Post operative management Initial managements include 1) Epithelial healing Immediately after the surgery , topical antibiotics are given, cycloplegic agents are instilled . The eye can be pressure patched with an antibiotic ointment or BSCL 2)Pain control Pain reduced by a combination of icepacks over orbit for several days , oral painkillers and neuropathic pain medications( gabapentin) The pain diminishes gradually as the epithelial defect resolves

59. complications Pain Poor epithelial healing Haze/scar Infection Induced hyperopia, regular and irregular astigmatism Decreased uncorrected and best corrected vision Recurrence of condition (11 percent)

60. Post operative haze over the first several weeks after surgery, the treated area may develop anterior stromal haze. If it is mild and without any symptoms, it can be followed up and it diminishes on its own. If it is more significant , topical steroids are helpful

61. Thank you