Medi Eslani

MIDTERM OUTCOMES OF AUTOLOGOUS CULTIVATED LIMBAL STEM CELL TRANSPLANTATION WITH OR WITHOUT PENETRATING KERATOPLASTY

Purpose: To report the midterm outcomes of autologous limbal stem cell transplantation cultivated on amniotic membrane (AM) with or without subsequent penetrating keratoplasty (PKP) in patients with total unilateral limbal stem cell deficiency (LSCD). Methods: Eight eyes of 8 consecutive patients with unilateral total LSCD underwent autologous limbal stem cell transplantation cultivated on AM. Four eyes underwent subsequent optical PKP. Main outcome measures were corneal vascularization and transparency. Results: The patients were followed for 34.0 ± 13.5 months (6-48 months). Seven cases had a stable corneal epithelium with marked decrease in opacification and vascularization. Progressive sectorial conjunctivalization was evident in all cases with subsequent PKP at the last follow-up. Primary failure was observed in one case because of exposure. Conclusions: Transplantation of autologous stem cells cultivated on AM with or without subsequent PKP seems to be an effective way for visual rehabilitation in total LSCD. More work with more cases and longer follow-up are needed to optimize this procedure to provide and maintain an adequate supply of limbal stem cells in these patients.

Limbal Stem Cell Deficiency in Chronic and Delayed-onset Mustard Gas Keratopathy

PURPOSE To evaluate limbal stem cell deficiency (LSCD) using impression cytology in patients with chronic and delayed-onset mustard gas keratopathy (MGK). DESIGN Prospective observational case series. PARTICIPANTS Thirty-five eyes of 18 patients (all male) with MGK were included. METHODS A consecutive series of patients with MGK underwent impression cytology. Finding of goblet cells on the corneal side of specimens was considered as LSCD. Severity of corneal clinical manifestation was graded as mild, moderate, and severe in each quadrant. Relation between impression cytology findings and clinical grading was evaluated. MAIN OUTCOME MEASURES Impression cytology findings and clinical grading. RESULTS There was LSCD in at least 1 quadrant of cornea in all 35 eyes (100% of cases). No differences were found between impression cytology findings (positive vs. negative for corneal goblet cells) among different quadrants (P = 0.378). Clinical grading was the same between nasal and temporal quadrants (P = 0.266) and between superior and inferior quadrants (P = 0.263). By combining superior and inferior quadrants (vertical zone) and nasal and temporal quadrants (horizontal zone), corneal clinical grading was more severe in horizontal versus vertical zones (P<0.001). There was no relation between LSCD and corneal clinical severity (P = 0.893). CONCLUSIONS A varying degree of LSCD was demonstrated in all patients with chronic or delayed-onset MGK using impression cytology. Corneal clinical manifestations are more severe in nasal and temporal quadrants. There was no relation between impression cytology findings (positive vs. negative for goblet cells) and corneal clinical grading. Other factors, such as perilimbal conjunctival ischemia, may play a role.

Anwar versus Melles Deep Anterior Lamellar Keratoplasty for Keratoconus: A Prospective Randomized Clinical Trial

PURPOSE To compare the outcomes of 2 techniques (Anwar vs. Melles) of deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. DESIGN Randomized, double-blind clinical trial. PARTICIPANTS Fifty-seven eyes of 57 patients 20 to 35 years of age were enrolled. METHODS Patients with clinical diagnosis of keratoconus who were contact lens intolerant and whose corrected distance visual acuity (CDVA) was less than 20/80 were enrolled. Eligible eyes were allocated randomly into 2 groups: the Anwar technique (23 eyes) or the Melles technique (25 eyes). MAIN OUTCOME MEASURES The primary outcome measure was CDVA. Secondary outcomes were spherical equivalent, contrast sensitivity, corneal aberrations, corneal biomechanical properties, endothelial cell count, and central corneal thickness. All outcomes were compared 15 months after surgery. RESULTS The CDVA was 0.17 ± 0.09 logarithm of the minimum angle of resolution (logMAR) units and 0.18 ± 0.11 logMAR units in the Anwar and Melles groups, respectively (P = 0.803). Spherical equivalent was -1.82 ± 2.7 diopters (D) and -2.69 ± 3.94 D in the Anwar and Melles groups, respectively (P = 0.155). Overall, the difference in photopic and mesopic contrast sensitivity function between the 2 groups was statistically significant (P<0.05). There was no significant difference between 2 groups in total and higher-order aberrations up to the fifth order (P>0.05 for all parameters). Corneal hysteresis was not significantly different between the 2 groups (9.9 ± 0.8 vs. 9.9 ± 0.6; P = 0.606). The corneal resistance factor was 10.02 ± 0.8 and 10.13 ± 0.76 (P = 0.509). There was no significant difference in percentage of endothelial cell loss between the 2 groups (1 ± 2% vs. 1 ± 3% in the Anwar and Melles groups, respectively; P = 0.869). Mean central corneal thickness was 525.56 ± 47.87 μm versus 504.64 ± 54.20 μm in the Anwar and Melles groups, respectively (P = 0.155). CONCLUSIONS The Anwar and Melles techniques of DALK have comparable visual acuity and refractive outcomes, aberrometric profiles, biomechanical properties, corneal thicknesses, and endothelial cell densities. However, patients who underwent the Anwar technique showed better contrast sensitivity.

Long-term evaluation of complications and results of photorefractive keratectomy in myopia: an 8-year follow-up.

Purpose: To evaluate 8-year results of photorefractive keratectomy (PRK) for myopia in terms of safety, efficacy, stability, and late complications. Methods: From 371 myopic eyes of 203 patients who underwent PRK using NIDEK EC-5000 excimer laser with 5.5- to 6-mm ablation zones in Basir Eye Center, Tehran, Iran, during 1997-1998, data of 179 myopic eyes of 98 patients, who participated in annual examinations, were analyzed. Treated eyes were divided into 3 groups according to preoperative refraction: low myopia [≤−6.00 diopters (D)], moderate myopia (−6.10 to −10.00 D), and high myopia (>−10.00 D). The main outcome measures were safety, efficacy, stability, and postoperative complications. Results: Eight years after PRK, 69.64%, 44.44%, and 45.65% of the low, moderate, and high myopic groups were within ±0.5 D of emmetropia. Sixteen eyes (4.31% of original cases) underwent retreatment mainly because of regression. Although a small myopic shift occurred up to 8 years after surgery, changes in myopic regression stabilized in all myopic groups within 24 months. Four eyes (2.06%) lost 2 lines of best spectacle-corrected visual acuity (1 eye for corneal haze and other 3 for problems not related to refractive surgery). Corneal haze occurred in 11.34% especially in medium and high myopic groups, but it cleared within 2 years in 68.2% of cases. Conclusions: Based on our study, PRK seems to be a safe, efficient, and stable surgical procedure, and if patients obtain a good result with the initial treatment, then their results are relatively stable over time.

Cultivated Limbal and Oral Mucosal Epithelial Transplantation

Stem cells located at the limbus are the ultimate source for regeneration of the corneal epithelium in normal and traumatized states. When limbal stem cells are dysfunctional or deficient, limbal stem cell deficiency (LSCD) develops. Its surgical management depends on laterality and severity of corneal-limbal involvement. Conventional methods of stem cell transplantation are conjunctival-limbal autograft (CLAU), conjunctival-limbal allograft (CLAL), and kerato-limbal allograft (KLAL) surgeries. Cultivated limbal epithelial transplantation (CLET) and cultivated oral mucosal epithelial transplantation (COMET) on a carrier such as amniotic membrane are current surgical alternatives. These new surgical procedures are effective in stabilizing the ocular surface. The theoretical advantage of ex-vivo expansions over conventional methods is that only a small limbal or mucosal biopsy is needed, thus minimizing the risk to the donor eye; there is also a lower risk of rejection. They can be used in cases with unilateral or bilateral total stem cell deficiency. In the unilateral cases, the source for CLET is a healthy fellow eye and in bilateral cases the source can be living-related or cadaveric eyes. The oral explants do not have limbal stem cells, but they seem to be a source of limbal stem cell equivalents that are able to generate cornea-like epithelium under the proper culture conditions. The main advantage of COMET is that patients with bilateral LSCD can be treated with grafts derived from their own autologous oral mucosal cells. The long-term outcomes of COMET have to be elucidated.

The Role of Toll-Like Receptor 4 in Corneal Epithelial Wound Healing

PURPOSE We evaluated the role of Toll-like receptor 4 (TLR4) in corneal epithelial wound healing. METHODS The expression of TLR4 during in vivo corneal epithelial wound healing was examined by immunostaining in mice. The expression and activation of TLR4 was studied in primary or telomerase-immortalized human corneal epithelial cells (HCEC). Scratch assay was performed to evaluate in vitro wound closure using live time-lapse microscopy. Transwell migration assay and Ki67 immunostaining were done to evaluate migration and proliferation, respectively. Lipopolysaccharide (LPS) was used to activate TLR4, whereas CLI-095 was used for its inhibition. The expression of inflammatory cytokines was determined by RT-PCR and ELISA. The activation of p42/44 and p38 was determined by immunoblotting. RESULTS In the murine model, TLR4 immunostaining was noted prominently in the epithelium 8 hours after wounding. There was a 4-fold increase in the expression of TLR4 6 hours after in vitro scratch wounding (P < 0.001). Confocal microscopy confirmed the membrane localization of TLR4/MD2 complex. There was a significant increase in migration, proliferation, and wound closure in HCEC treated with LPS (P < 0.05), while there was significant decrease with TLR4 inhibition (P < 0.05). Addition of LPS to wounded HCEC resulted in a significant increase in the expression of IL-6, TNF-α, CXCL8/IL8, and CCL5/RANTES at the mRNA and protein levels. Likewise, LPS increased the activation of p42/44 and p38 in wounded HCEC. CONCLUSIONS These results suggest that epithelial wounding induces the expression of functional TLR4. Toll-like receptor 4 signaling appears to contribute to early corneal epithelial wound repair by enhancing migration and proliferation.

Postoperative complications of conjunctival limbal autograft surgery.

Purpose: To report postoperative complications of conjunctival limbal autograft in patients with unilateral total limbal stem cell deficiency (LSCD). Methods: In this retrospective observational case series, medical charts of 34 patients with unilateral total LSCD with at least 6 months of follow-up were reviewed. Main outcome measure was postoperative complications. Results: The mean follow-up period was 17.2 ± 6.3 (range, 6–33) months. The postoperative complications observed included conjunctival encroachment over the graft, small graft, graft dislodging, thick graft, improper position, graft edema, ocular surface exposure, progressive horizontal conjunctivalization, and pyogenic granuloma. Persistent epithelial defect occurred in 5 eyes because of ocular surface exposure (n = 2), conjunctival encroachment (n = 1), and small graft size (n = 2). Epithelial defects healed in 4 of them with sectoral vascularization of the cornea. Optical penetrating keratoplasty was performed on 18 eyes with dense corneal opacification. Persistent epithelial defect occurred in 6 eyes with inadvertent cut limbal graft (n = 2), small limbal graft (n = 2), and ocular surface exposure (n = 2). Conclusions: Conjunctival limbal autograft is an effective procedure for anatomical and visual rehabilitation of eyes with unilateral total LSCD. However, it may be complicated by several adverse events. The most common complications are related to the transplanted grafts (size, thickness, position, and alignment) and chronic ocular surface exposure, which may later lead to epithelial breakdown and corneal conjunctivalization.

Current and Upcoming Therapies for Ocular Surface Chemical Injuries

Chemical injuries frequently result in vision loss, disfigurement, and challenging ocular surface complications. Acute interventions are directed at decreasing the extent of the injury, suppressing inflammation, and promoting ocular surface re-epithelialization. Chronically, management involves controlling inflammation along with rehabilitation and reconstruction of the ocular surface. Future therapies aimed at inhibiting neovascularization and promoting ocular surface regeneration should provide more effective treatment options for the management of ocular chemical injuries.

Complications of keratolimbal allograft surgery.

Purpose: To report postoperative complications of keratolimbal allograft (KLAL) transplantation in patients with bilateral total limbal stem cell deficiency. Methods: In this retrospective observational case series, medical charts of 45 patients with at least 6 months of follow-up were reviewed. The main outcome measure was postoperative complications including graft-related issues (thickness, position, and alignment) and immunologic rejection. Results: Sixty-six KLALs were performed on 45 eyes. The mean follow-up period was 26.1 ± 11.8 months (range, 6–48 months). Primary failure occurred in 5 eyes primarily as a result of ocular surface exposure and severe dry eyes. Graft-related complications included misalignment (4 eyes), buttonhole (4), inner-edge tear (4), inadvertent limbal trephination (2), and thick KLAL (2). Postoperatively, regional thinning of the graft was observed in 8 KLALs as a result of exposure, regional ischemia, and after epithelial rejection. Acute rejection was diagnosed 16 times in 8 eyes, whereas chronic rejection was observed in 24 eyes. At last follow-up, 12 cases (26.6%) had failed because of recurrent acute rejection (4), chronic rejection (5), refractory herpetic keratitis (1), exposure (1), and refractory papillomavirus keratitis (1). Conclusions: KLAL may be complicated by several adverse events. The most important complications are immunologic rejections, chronic ocular surface exposure, and graft-related complications.

Effect of Timolol on Refractive Outcomes in Eyes With Myopic Regression After Laser In Situ Keratomileusis: A Prospective Randomized Clinical Trial

PURPOSE To compare the effects of timolol on refractive outcomes in eyes with myopic regression after laser in situ keratomileusis (LASIK) with a control-matched group. DESIGN Prospective, randomized, parallel-controlled, double-masked clinical trial. A computer-generated randomization list based on random block permutation (length 4 to 8) was used for treatment allocation. METHODS setting: Basir Eye Center, Tehran, Iran. PATIENT POPULATION Of 124 eyes with myopic regression after LASIK using Technolas 217-Z, 45 eyes in each group were analyzed. INTERVENTION Patients were randomly assigned into either Group 1, who received timolol 0.5% eye drops, or Group 2, who received artificial tears for 6 months. MAIN OUTCOME MEASURE Spherical equivalent (SE) at 6 months posttreatment. RESULTS In Group 1, SE improved from -1.48 ± 0.99 diopter (D) before treatment to -0.88 ± 0.91 D and -0.86 ± 0.93 D 6 months after treatment and 6 months after timolol discontinuation, respectively (P < .001). In Group 2, it was -1.57 ± 0.67 D, -1.83 ± 0.76 D, and -1.91 ± 0.70 D, respectively (P < .001). SE was significantly better in Group 1 6 months after treatment and 6 months after discontinuation of treatment (P < .001 for both comparisons). There was a 0.26 D decrease in SE improvement every 4 months after the surgery in the Group 1 (P < .001). CONCLUSIONS Timolol application is effective for the treatment of myopic regression after LASIK compared with control group. Its effects last for at least 6 months after its discontinuation.