The authors have no financial interest Early Changes in Corneal Sensation, Ocular Surface Integrity, Tear-Film Function, and Conjunctival Impression Cytology After Photorefractive Keratectomy Byeong Hee Lee, M.D. Young Jeung Park, M.D. Ph.D. Kyoo Won Lee, M.D. Ph.D. Cheil Eye Hospital , Daegu, Korea The authors have no financial interest

Background and purpose There are some reports detailing the course of corneal sensation, ocular surface integrity, and tear-film function after myopic surface ablation(PRK, LASEK) No previous reports on morphological alteration of the ocular surface after myopic surface ablation. To investigate the morphological alteration of the ocular surface, corneal sensation, ocular surface integrity, and tear-film function after photorefractive keratectomy (PRK)

Materials and Methods Prospective study: Included patients having myopic PRK surgery (25 patients, 50 eyes) PRK procedure Removal of corneal epithelium by Amoils epithelial scrubber® Technolas 217z 100® flying spot excimer laser was used on tissue saving mode Chilled balanced salt solution (BSS®) was used to irrigate, and bandage contact lenses were used to cover the cornea Antibiotics and anti-inflammatory eye drops were used until reepithelization of the cornea is completed, and bandage contact lenses were removed (3~5 days post-op.). Topical steroids were administered 4 times daily, and tapered to abstinence in span of 4 months

Evaluation Ocular surface disease index (OSDI) questionnaire Corneal sensation (Cochet-Bonnet esthesiometer) Tear-film breakup time (BUT) Schimer test without anesthesia (Schimer Ⅰ) Corneal fluorescein staining score (CFS): Using 4-point scale: 0 = no staining of the cornea, 1 = less than one-third staining, 2 = less than two-third staining, 3 = more than two-third staining Conjunctival impression cytology (CIC): Use filters composed of mixed esters of cellulose with submicroscopic pores (ML-Millipore) Instill anesthesia and then applied to the superior bulbar conjunctiva with forceps and pressed usually for 3-5 sec. After PAS stain, evaluated degree of squamous metaplasia, density of goblet cells (cell/mm2), snake-like chromatic change : Nelson’s classification Followed up at pre-op, 2nd week, 1, 2, 3, and 6 months post-op.

Patient and ocular characteristics. PRK Number of eyes (patients) 50 (25) Male/Female 6/19 Mean age of patients (years) (Range) 25.56±4.35 (19~35) CL history (years) 4.81±5.36 (0~20) Preoperative SE (Diopter) -4.80±1.64 (-1.75~-8.5) Preoperative pachymetry (μm) 543.7±30.2 (484~608) Ablation depth (μm) 82.39±22.04 (41~127) Ablation diameter (mm) 6.54±0.30 (6.0~7.2)

Clinical parameters before and after PRK . ‡ Parameter Preoperative Postoperative 2 Week 1 Months 2 Months 3 Months 6 Months Conjunctival epithelial metaplasia 0.72±0.74 1.74±0.56* 1.82±0.54* 1.23±0.65* 0.96±0.69 0.51±0.49 Goblet cell count (cell/mm2) 226.2±154.2 77.0±56.3* 135.7±133.5* 205.6±111.1 265.0±168.1 348.4±188.3† Corneal sensation (mm) 56.00±4.30 50.00±5.20* 52.00±5.20* 56.80±2.84 57.20±3.84 59.00±2.04† Corneal fluorescein staining 0.72±1.21 1.6±1.22* 0.48±0.65 0.48±0.71 0.36±0.76* 0.44±0.77 OSDI§ 29.16±22.71 36.86±13.79* 27.53±13.77 25.01±13.13 21.25±10.65 20.84±12.42 BUT∥ (seconds) 4.00±3.66 4.60±2.89 4.92±2.60 4.04±2.62 4.88±3.00 5.00±3.07 Schimer I (mm) 13.6±12.25 11.28±9.24 10.88±8.14 9.16±7.59* 8.32±9.32* 9.60±5.35 * Significantly worse than the preoperative value (p<.05, Wilcoxon signed-rank test); † Significantly better than the preoperative value (p<.05, Wilcoxon signed-rank test); ‡ PRK = photorefractive keratectomy; § OSDI = ocular surface disease index; ∥ BUT = tear break-up time

E:3 months post-op F:6 months post-op D:2 months post-op Grade of conjunctival epithelial metaplasia as time progresses. Graph shows that epithelial metaplasia grade worsens drastically up to two weeks post-op, maximizing at 4 weeks post-op. Then it improves gradually, returning to pre-op level at 3 months post-op, yet to improve further all the way to 6 months post-op. E:3 months post-op F:6 months post-op D:2 months post-op C:1 month post-op A: pre-op Grade:1 N/C 1:3 Snake-like chromatin Grade:0 N/C 1:2 Grade:0 N/C 1:2↓ B:2 weeks post-op Grade:2 N/C 1:4

Goblet cell densities from pro-op to 6 months post-op. Graph exhibits a sharp reduction in goblet cells at 2 weeks post-op, then shows a gradual recovery returning to pre-op level at between 2 ~ 3 months post-op. The increase in goblet cell numbers continues to 6 months post-op A:pre-op B: 2 weeks post-op C: 1 month post-op D: 2 months post-op E: 3 months post-op F: 6 months post-op

Snake-like chromatin pattern The number of snake-like chromatin patterns: the relative percentage in the cell layers of the specimens obtained ranging from 0 to more than 75% (0= no snakes; Ⅰ= 1-10%; Ⅱ= 11-25%; Ⅲ= 26-50%; Ⅳ= 51-75%; Ⅴ= >75%) Snake-like chromatin pattern increase 20.0% between 1~3 months post-op. However, it decreases back to pre-op level at 6 months post-op. Snake-like chromatin pattern also showed increase in amount in individual case in afore mentioned period.

conclusions Corneal sensation decrease all the way to 2 weeks post-op, then bounces back gradually to pre-op level 2 months post-op. CFS was the highest at 2 weeks post-op. It decrease to even below the pre-op level at 4 weeks post-op. OSDI was the highest at 2 weeks post-op, then gradually decreasing all the way to 6 months post-op. BUT showed minimal changes throughout the period of pre-op and follow-ups. Schimer Ⅰtest decrease gradually. It shows marginal drop between 2~ 3months post-op when compared against pre-op level. As seen on this research corneal sensation, CFS, and OSDI turned out to be good indicator of clinical progress after PRK, whereas BUT and Schimer Ⅰtest turned out insufficient clinical indicators.

conclusions The first drastic change on conjunctival impression cytology(CIC) after PRK is the decrease in goblet cell count, which bottoms out at 2 weeks post-op. Then the conjunctival epithelial metaplasia grade increase drastically and peaks out at 4 weeks post-op. Goblet cell count recovers to pre-op level at 2~ 3 months post-op, whereas conjunctival epithelial metaplasia grade returns to pre-op level at 3~6 months post-op. Follow up of ocular surface health after 6 months of PRK seems necessary; although, corneal sensation and healing for corneal surface show improvement two months after PRK, conjunctival surface morphology shows improvement at least after six months of PRK. It seems further study on precise mechanism of ocular surface modulation after PRK is essential.

The End Thank you for your attention