Hosam Sheha

Update on amniotic membrane transplantation

Cryopreserved amniotic membrane modulates adult wound healing by promoting epithelialization while suppressing stromal inflammation, angiogenesis and scarring. Such clinical efficacies of amniotic membrane transplantation have been reported in several hundred publications for a wide spectrum of ophthalmic indications. The success of the aforementioned therapeutic actions prompts investigators to use amniotic membrane as a surrogate niche to achieve ex vivo expansion of ocular surface epithelial progenitor cells. Further investigation into the molecular mechanism whereby amniotic membrane exerts its actions will undoubtedly reveal additional applications in the burgeoning field of regenerative medicine. This article will focus on recent advances in amniotic membrane transplantation and expand to cover its clinical uses beyond the ocular surface.

Pathogenic role of Demodex mites in blepharitis.

Purpose of reviewTo summarize the key literature and our research experience regarding Demodex infestation as a potential cause of ocular inflammatory diseases with a special emphasis on Demodex blepharitis. Recent findingsTwo distinct Demodex species have been confirmed as a cause of blepharitis: Demodex folliculorum can cause anterior blepharitis associated with disorders of eyelashes, and D. brevis can cause posterior blepharitis with meibomian gland dysfunction and keratoconjunctivitis. Tea tree oil treatments with either 50% lid scrubs or 5% lid massages are effective in eradicating mites and reducing ocular surface inflammation. SummaryDemodex blepharitis is a common but overlooked external eye disease. The pathogenesis of Demodex blepharitis in eliciting ocular surface inflammation has been further clarified. The modified eyelash sampling and counting method makes it easier and more accurate to diagnose Demodex infestation. Tea tree oil shows promising potential to treat Demodex blepharitis by reducing Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.

Long-term Outcomes of Keratolimbal Allograft for Total Limbal Stem Cell Deficiency Using Combined Immunosuppressive Agents and Correction of Ocular Surface Deficits

OBJECTIVE To determine the long-term outcomes of keratolimbal allograft (KLAL). METHODS Scores of such risks as infrequent blinking, blink-related microtrauma, conjunctival inflammation, elevated intraocular pressure, dry eye, symblepharon, lagophthalmos, and previous KLAL or penetrating keratoplasty (PKP) failure were calculated and recorded before, during, and after KLAL. Prolonged oral mycophenolate mofetil and tacrolimus and short-term prednisone and acyclovir were administered in 12 eyes (10 consecutive patients) with total limbal stem cell deficiency after KLAL. Ten eyes underwent subsequent PKP. RESULTS More corrective measures were required in eyes with higher risk scores. During a follow-up of 61.2 months (standard deviation [SD], 18.2; range, 36-91 months) after KLAL, postoperative epithelial breakdown due to exposure occurred late in the period after PKP and remained a primary risk. Mean daily doses of 1.4 g of mycophenolate mofetil and 1.6 mg of tacrolimus were administered for 52.7 months (SD, 22.5; range, 23-91 months) with few adverse effects and reached trough levels of 1.6 microg/mL (SD, 0.6 microg/mL) and 4.5 ng/mL (SD, 2 ng/mL), respectively. Keratolimbal allograft and PKP rejection was noted in 2 and 3 eyes, respectively, though there was a reversal in 1 eye in each group, yielding final KLAL and PKP survivals in 10 and 8 eyes, respectively, and ambulatory visual acuity of up to 20/20 in 10 eyes for 67.2% of the entire follow-up period. CONCLUSION Correction of ocular surface deficits combined with an immunosuppressive regimen further improves the long-term outcome of KLAL in eyes with total limbal stem cell deficiency.

Role of conjunctival inflammation in surgical outcome after amniotic membrane transplantation with or without fibrin glue for pterygium.

Purpose: To determine the clinical significance of postoperative conjunctival inflammation noted at the third or fourth week after intraoperative application of mitomycin C and amniotic membrane transplantation for pterygium. Methods: This retrospective study included 27 eyes of 23 patients with primary (n = 12) or recurrent (n = 15) pterygia. All cases were operated by extensive removal of subconjunctival fibrovascular tissue and intraoperative application of 0.04% mitomycin C in the fornix, followed by amniotic membrane transplantation by using either fibrin glue (14 eyes) or sutures (13 eyes). Main outcome measures included development of conjunctival inflammation, pyogenic granuloma, and pterygium recurrence after surgery. Results: For a follow-up of 29.6 ± 17.2 months (range, 6-56 months), 16 (59.3%) eyes without postoperative conjunctival inflammation resulted in favorable outcomes. Conjunctival inflammation around the surgical site was noted in the remaining 11 (40.7%) eyes and was significantly more common in eyes with sutures than those with fibrin glue (61.5% vs. 21.4%, respectively; P = 0.05). Among those with this inflammation, 7 eyes receiving subconjunctival injection of triamcinolone resulted in complete resolution and a good aesthetic outcome. Four eyes without this injection gradually developed conjunctival (n = 1) or corneal (n = 1) recurrence and/or pyogenic granuloma (n = 3). Conclusions: Host conjunctival inflammation is still common after intraoperative application of mitomycin C and amniotic membrane transplantation, especially when sutures are used in pterygium surgery. If left untreated, persistent inflammation may lead to a poor surgical outcome.

Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea

PURPOSE To investigate correlation between ocular Demodex infestation and serum. DESIGN A prospective study to correlate clinical findings with laboratory data. PARTICIPANTS We consecutively enrolled 59 patients: 34 men and 25 women with a mean age of 60.4+/-17.6 years (range, 17-93). METHODS Demodex counting was performed based on lash sampling. Serum immunoreactivity to two 62-kDa and 83-kDa proteins derived from B oleronius was determined by Western blot analysis. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography and graded in a masked fashion. MAIN OUTCOME MEASURES Statistical significance based on correlative analyses of clinical and laboratory data. RESULTS These 59 patients were age matched, but not gender matched, regarding serum immunoreactivity, ocular Demodex infestation, or facial rosacea. There was a significant correlation between serum immunoreactivity and facial rosacea (P = 0.009), lid margin inflammation (P = 0.040), and ocular Demodex infestation (P = 0.048), but not inferior bulbar conjunctival inflammation (P = 0.573). The Demodex count was significantly higher in patients with positive facial rosacea (6.6+/-9.0 vs. 1.9+/-2.2; P = 0.014). There was a significant correlation of facial rosacea with lid margin inflammation (P = 0.016), but not with inferior bulbar conjunctival inflammation (P = 0.728). Ocular Demodex infestation was less prevalent in patients with aqueous tear-deficiency dry eye than those without (7/38 vs. 12/21; P = 0.002). CONCLUSIONS The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation.

Oral Mucosal Graft With Amniotic Membrane Transplantation for Total Limbal Stem Cell Deficiency

PURPOSE To report the results of oral mucosal graft for reconstruction of corneas with total limbal stem cell deficiency. DESIGN Retrospective, interventional case series. METHODS Seven patients (7 eyes) with total limbal stem cell deficiency caused by chemical burn (4 eyes), Stevens-Johnson syndrome / toxic epidermal necrolysis (1 eye), ocular cicatricial pemphigoid (1 eye), and multiple cryotherapies and application of mitomycin C for conjunctival melanoma (1 eye) were enrolled in this study. Oral mucosal graft was transplanted as a surrogate limbus together with amniotic membrane transplantation with a follow-up of at least 8 months. Symptomatic relief, restoration of a stable epithelium, corneal clarity, and the best-corrected visual acuity were assessed. RESULTS Limbal stem cell deficiency was confirmed by impression cytology in all eyes, among which 6 were bilateral while 1 was unilateral. All 7 patients presented with severe loss of vision, photophobia, pain, chronic inflammation, and corneal vascularization and scarring. For 30 ± 19.8 months, pain and photophobia were resolved in all 7 eyes; 6 eyes exhibited a stable epithelium with regressed corneal vascularization and reduced chronic inflammation. Visual acuity was improved in all 7 eyes. One eye developed partial limbal stem cell deficiency due to exposure at 47 months follow-up and was reoperated. Five eyes had peripheral corneal vascularization. CONCLUSIONS Oral mucosal graft is a viable alternative for treating total limbal stem cell deficiency in eyes where transplantation of allogeneic limbal stem cells has failed or is not feasible.

Sutureless Amniotic Membrane Transplantation for Severe Bacterial Keratitis

Purpose: To evaluate the efficacy of early sutureless amniotic membrane transplantation in the management of severe bacterial keratitis to reduce pain, inflammation, and haze, and to promote healing. Method: A noncomparative case series including 3 eyes of 3 consecutive patients with severe bacterial keratitis exhibiting persistent epithelial defect/ulcer, more than 5 mm in diameter, located within 3mm from the visual axis with infiltration occupying more than 50% of the corneal thickness. They were retrospectively reviewed following early (ie, within 96 hours) sutureless amniotic membrane transplantation via ProKera together with selective topical antibiotics and preservative-free steroid. Pain relief, inflammation, haze, and corneal epithelial healing were monitored. Results: ProKera was inserted once in 1 eye and twice in the other 2 eyes. Pain was significantly relieved and inflammation was markedly reduced in all cases. The corneal epithelial defect and stromal ulceration rapidly healed while visual acuity improved in 2 of the 3 eyes. Conclusion: Temporary sutureless amniotic membrane transplantation via ProKera allows easy insertion and replacement of the membrane in the office, as well as early intervention to promote epithelialization, reduce pain, haze and inflammation in cases with severe bacterial keratitis. This result justifies large series controlled studies in the future.

Ocular demodicosis as a potential cause of pediatric blepharoconjunctivitis.

Purpose: To report Demodex infestation in pediatric blepharoconjunctivitis. Methods: A retrospective review of 12 patients, with ages from 2.5-11 years, with chronic blepharoconjunctivitis who failed to respond to conventional treatments. Demodex was detected by lash sampling and microscopic examination. Patients were treated with 50% tea tree oil (TTO) eyelid scrubs or 5% TTO ointment eyelid massages for 4-6 weeks. Results: Demodex mites were found in all, but 1 case had cylindrical dandruff in the lashes. After 1 week of TTO treatment, all patients showed dramatic resolution of ocular irritation and inflammation while Demodex counts dropped. All corneal signs resolved within 2 weeks except for a residual anterior stromal scar in 1 eye. During a follow-up period of 8.3 ± 4.6 months, 1 patient showed recurrent inflammation, which was successfully managed by a second round of TTO treatment. Conclusions: Demodicosis should be considered as a potential cause of pediatric refractory blepharoconjunctivitis. Eyelid scrubs or massage with TTO could be an effective treatment regimen in these cases.

Recent advances on ocular Demodex infestation.

Purpose of review To summarize recent advances on ocular Demodex infestation. Recent findings Demodex infestation is a potential cause of ocular surface inflammation. The pathogenesis of Demodex in eliciting ocular surface inflammation has been further clarified. Cliradex is currently the treatment of choice, it comprises the most active ingredient of tea tree oil, that is terpinen-4-ol, which helps eradicate Demodex mites and reduce ocular surface inflammation. Summary Ocular demodicosis is a common but overlooked eye disease that manifests a number of morbidities. Demodex folliculorum causes chronic anterior blepharitis whereas Demodex brevis causes posterior blepharitis, meibomian gland dysfunction, recurrent chalazia, and refractory keratoconjunctivitis. The lash sampling and microscopic counting method and in-vivo confocal microscopy are key diagnostic methods. Cliradex shows promising potential to reduce Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.

Ocular Demodicosis as a Risk Factor of Pterygium Recurrence

PURPOSE To evaluate ocular demodicosis as a potential risk factor in pterygium recurrence. DESIGN Cross-sectional study to correlate clinical findings with laboratory data. PARTICIPANTS We retrospectively reviewed 94 patients (43 with primary and 51 with recurrent pterygia), among whom 68 patients received surgical correction, and prospectively enrolled another 23 pterygium patients and 14 nonpterygium controls for measuring the tear level of interleukin (IL)-17. METHODS All patients had microscopically confirmed ocular demodicosis. Statistical correlations were analyzed among age, sex, aqueous tear deficiency, dry eye, ocular demodicosis, follow-up period, surgical outcome, and tear levels of IL-17 measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES Correlation between ocular demodicosis or IL-17 levels and pterygium recurrence. RESULTS Among 94 patients, ocular demodicosis was more prevalent in patients with recurrent pterygium than those with primary pterygium (P = 0.015). During follow-up of 16.5 ± 11.5 months, 68 postsurgical patients developed 7 corneal recurrences, which constituted 7.4% of primary and 12.2% of recurrent pterygium (P = 0.820). They also developed 8 conjunctival recurrences. Kaplan-Meier survival analysis showed combined (P = 0.000), corneal (P = 0.044), and conjunctival (P = 0.002) recurrence was significantly higher among patients with demodicosis than those without. Conjunctival recurrence occurred within 6 months in eyes without demodicosis but extended beyond 6 months in eyes with demodicosis. In 34 postsurgical patients with demodicosis, the mite count of 14 patients with recurrence was significantly higher than that of 20 without (P = 0.005). The IL-17 level was significantly higher in patients with either pterygium or demodicosis than controls (P = 0.049 and 0.040, respectively), and the IL-17 level was further elevated in patients with both pterygium and demodicosis (all P<0.05). CONCLUSIONS Ocular demodicosis is a risk factor for pterygium recurrence, especially for conjunctival recurrence, presumably by perpetuating chronic inflammation mediated by T-helper (Th)17 lymphocytes.