Steroid-eluting contact lenses for corneal and intraocular inflammation.

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.

Correlation analysis of the clinical features and prognosis of acute ocular burns-exploration of a new classification scheme.

PURPOSE: To explore a new classification scheme for acute ocular burns. METHODS: Medical records of 345 patients (450 eyes) with acute ocular burns treated at Shandong Eye Institute between January 2013 and January 2018 with a 12-month minimum follow-up were retrospectively reviewed. A total of 8 parameters in the acute phase were evaluated and graded on a scale from 0 to 3 according to their severity. RESULTS: The key factors affecting the prognosis of acute ocular burns were conjunctival involvement (386 eyes, 85.8%), corneal epithelial defect (349 eyes, 77.6%), and limbal ischemia (244 eyes, 54.2%). Visual acuity in 181/450 eyes (40.2%) was worse than 6/60. The injury severity of the cornea, limbus, bulbar conjunctiva, eyelid, and fornix and intraocular signs in the acute phase was significantly correlated with the logarithm of the minimum angle of resolution (logMAR) visual acuity (correlation coefficient [R] 0.481-0.933, P < 0.0001) and corneal opacification, neovascularization, and symblepharon scores in the stable phase (R 0.513-0.855, P < 0.0001). The mean total score for the 8 parameters in the acute phase was 5.34 ± 4.04 (range 0-14); higher scores indicated worse visual acuity (R = 0.899, P < 0.0001). The total score for acute-phase parameters was significantly correlated with that for the stable-phase parameters (R = 0.872, P < 0.0001). CONCLUSIONS: The severity of acute-phase parameters is significantly correlated with the final visual outcome and prognosis. The new grading scheme can help clinicians more accurately analyze the degree of ocular burns, determine a reasonable treatment protocol, and rationally evaluate the prognosis.

Indications for penetrating keratoplasty and anterior lamellar keratoplasty during 2010-2017.

AIM: To review the indications of penetrating keratoplasty (PK) and anterior lamellar keratoplasty (ALK) at Qingdao Eye Hospital, Shandong Eye Institute, Qingdao, China, from 2010 to 2017. METHODS: The data of all patients undergoing PK or ALK from January 2010 to December 2017 was retrospectively reviewed, with the indications during 2010-2013 and 2014-2017 compared. RESULTS: A total of 1869 eyes were included, among which 1405 eyes (75.2%) had PK and 464 eyes (24.8%) had ALK. The leading indications were suppurative keratitis (36.8%), keratoconus (15.5%), herpes keratitis (13.1%), and regraft (10.5%). In eyes undergoing PK, the top four indications were suppurative keratitis (38.7%), herpes keratitis (15.3%), keratoconus (12.6%), and regraft (12.5%) during 2014-2017, with the proportion of suppurative keratitis and herpes keratitis decreased while regraft and keratoconus increased compared with 2010-2013. In eyes with ALK, suppurative keratitis (30.8%), keratoconus (24.1%), corneal dystrophies and degenerations (10.6%), and corneal dermoid tumor (9.7%) were the top four indications, and there was no significant difference for the proportion of each indication between 2010-2013 and 2014-2017. CONCLUSION: Suppurative keratitis is the most common indication for PK and ALK at Qingdao Eye Hospital during 2010-2017, followed by keratoconus, herpes keratitis, and regraft. In eyes treated with PK, the proportion of suppurative keratitis and herpes keratitis decrease while regraft and keratoconus increase during 2014-2017 compared with 2010-2013.

Topical sustained drug delivery to the retina with a drug-eluting contact lens.

Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.

Comparison of the efficacy of different cell sources for transplantation in total limbal stem cell deficiency.

PURPOSE: The purpose of this study was to compare the efficacy of allogeneic cultured limbal epithelial transplantation (ACLET) and cultivated oral mucosal epithelial transplantation (COMET) in treating total limbal stem cell deficiency (LSCD). METHODS: In this retrospective cohort study, 73 patients (76 eyes) with total LSCD, including 41 patients (42 eyes) treated with ACLET and 32 patients (34 eyes) receiving COMET, were evaluated. The age, gender and injury cause of all patients were recorded. RESULTS: The mean follow-up was 23.3 ± 9.9 months in the ACLET group and 16.1 ± 5.8 months in the COMET group. A higher incidence of persistent epithelial defect was observed after COMET (P = 0.023). The overall ocular surface grading scores were all lower in the ACLET group than in the COMET group at 3, 6, and 12 months after surgery and the last follow-up. Kaplan-Meier survival curve analysis demonstrated a significantly higher success rate of ACLET (71.4%), compared with that of COMET (52.9%; P = 0.043). The risk of graft failure was higher in patients with entropion and trichiasis, incomplete eyelid closure and treated with COMET. The graft failure risk rate after COMET was 3.5 times higher than that of ACLET. CONCLUSIONS: For total LSCD patients, ACLET should be prioritized, since limbal epithelial cells have better ability to maintain corneal epithelial integrity and ocular surface stability and benefit the ocular surface when compared with oral mucosal epithelial cells. Preoperative and postoperative eyelid abnormalities should be corrected as early as possible.

Resolution of fluoroquinolone-resistant Escherichia coli keratitis with a PROSE device for enhanced targeted antibiotic delivery.

PURPOSE: To report the resolution of a fluoroquinolone-resistant Escherichia coli keratitis with use of a prosthetic replacement of the ocular surface ecosystem (PROSE) device for enhanced targeted delivery of moxifloxiacin. OBSERVATIONS: A 62-year-old female presented with a 3-day history of pain, photophobia, and declining vision in left eye. The patient had a 2-year history of binocular PROSE treatment for ocular chronic graft-vs-host disease (cGVHD). A corneal ulcer was diagnosed and treated with topical 0.5% moxifloxacin solution 6 times per day, with continued wear of the PROSE device. After 4 days, worsening symptoms led to an increase in application of moxifloxicin to every 2 hours while awake. The drug was administered by removal of the device, cleaning and replenishing the reservoir with sterile saline, and adding one drop of the drug to the reservoir prior to reinsertion. Four days later, the corneal surface was epithelialized with only small subepithelial infiltrate remaining. The corneal culture grew an E. coli isolate carrying multiple mutations in the topoisomerase genes. These mutations were correlated with varying levels of resistance to ciprofloxacin (256 µg/mL), levofloxacin (8 µg/mL), and moxifloxacin (16 µg/mL). CONCLUSIONS AND IMPORTANCE: Although the infecting E. coli strain exhibited resistance to fluoroquinolones, the infection resolved when moxifloxacin was combined with PROSE therapy. Frequent dosing to the PROSE reservoir is likely to increase fluoroquinolone bioavailability and may represent a valuable approach to overcome antibiotic resistance.

Etiology and failure analysis of anterior lamellar keratoplasty.

AIM: To analyze indications and reasons for failure of anterior lamellar keratoplasty (ALK). METHODS: The clinical records were retrospectively reviewed. Main outcome measures included indications for ALK and reasons for failure of ALK. RESULTS: A total of 434 patients (462 eyes) were treated with ALK at Qingdao Eye Hospital, Shandong Eye Institute from June 1, 2009 to May 31, 2016. The main indications were infectious keratitis (33.3%), keratoconus (23.6%), corneal dystrophy and degeneration (9.8%), Mooren's ulcer (8.4%), corneal neoplasm (7.8%), viral keratitis (6.5%) and regrafting (3.7%). Fungal keratitis accounted for 73.4% in the infectious keratitis cases. ALKs were failed in 36 patients, with the major causes being recurrence of primary diseases (63.9%). The leading causes of graft failure was Mooren's ulcer (36.1%), followed by infectious keratitis (30.6%). Recurrence of fungal keratitis accounted for 81.8% in the failed cases after ALK for infectious keratitis cases. CONCLUSION: Infectious keratitis and keratoconus are the main indications for ALK, of which fungal keratitis was the major cause of corneal infections. Recurrence of primary disease is the main reason of graft failure after ALK, in which the main primary diseases associated with graft failure are Mooren's ulcer and fungal keratitis.

Clinical analysis of fungal keratitis in patients with and without diabetes.

We compared the clinical characteristics, treatments, and prognoses of fungal keratitis in patients with and without diabetes. Patients diagnosed with fungal keratitis at Shandong Eye Institute between January 2010 and December 2016 were retrospectively reviewed and classified as diabetic and nondiabetic groups. One-hundred-and-eleven patients (111 eyes) with diabetes and 740 patients (740 eyes) without diabetes were included. The diabetic patients showed significantly older (p< 0.05) and lower male:female ratio (p<0.05). Plants trauma was the primary risk factor in both groups, and there was no significant difference of pathogen type (the most common was Fusarium genus, followed by Alternaria and Aspergillus genera). Multivariate logistic regression analyses revealed that diabetes and topical glucocorticoid use were the independent risk factors for the severity of fungal keratitis. The recurrent infection rate between the diabetic and nondiabetic patients during the follow-up (6 to 24 months) after penetrating keratoplasty (PKP) was not significantly different. Although the recurrent epithelial defect, rejection, and best-corrected visual acuity were similar between the patients with matched bed/graft size (7.75/8.0 mm) in the two groups 1 year after PKP, the incidence of delayed re-epithelialization (>7 days) was significantly higher in diabetic patients (3/10 versus 2/43 in nondiabetic patients, p<0.05). More specially, the diabetic patients with the duration ≥10 years showed more significantly delayed re-epithelialization than those with the diabetic duration less than 10 years (3/5 versus 1/26, p<0.05). In conclusion, the diabetes mellitus is an independent risk factor that affect the severity of fungal keratitis. Corneal re-epithelialization was significantly delayed after PKP in the diabetic patients, especially with the duration ≥10 years.

A comparative study of risk factors for corneal infection in diabetic and non-diabetic patients.

AIM: To compare the clinical characteristics of infectious keratopathy in type 2 diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) and to investigate risk factors for infectious keratopathy in T2DM patients. METHODS: Totally 230 patients with T2DM and 168 with NDM diagnosed as infectious keratopathy were hospitalized at Qingdao Eye Hospital from 2001 to 2015. Data including sex, age, occupation, season, smoking and alcohol consumption habits, duration between onset and treatments, duration of hospitalization were collected. Initially identified indicators were analyzed with a multivariate logistic regression. Glycosylated hemoglobin A1c (HbA1c) in patients with T2DM was analyzed. The infectious keratopathies in the two groups were categorized and compared. RESULTS: The diabetic group consisted of 146 (63.5%) males and 84 (36.5%) females. The NDM group consisted of 111 (66.1%) males and 57 (33.9%) females. There was no signigicantly difference in sex distribution between the two groups (P>0.05). There were significant differences in age, occupation of patients, season of the onset of diseases, duration between onset and treatment, and durations of hospitalization between the two groups (P<0.05). In most of the patients in the diabetic group, the duration between onset and treatment was ≤3mo, and most was ≥3mo in the NDM group. Multivariate logistic regression analysis revealed that age and season were related to the development of corneal infection in the T2DM group (OR=1.709, 1.706). In the T2DM group, HbA1c was 9.09%±2.12%. There were statistically significant differences in the incidences of bacterial keratitis and herpes simplex keratitis in the two groups (P<0.05), but no significant statistical difference was found between fungal keratitis and amoebic keratitis (P>0.05). CONCLUSION: Advanced age and the summer and winter seasons are identified as risk factors for infectious keratopathy in T2DM patients, and T2DM patients are more prone to bacterial keratitis.

Therapeutic Effects of Lamellar Keratoplasty on Terrien Marginal Degeneration.

PURPOSE: To evaluate the therapeutic effects of lamellar keratoplasty (LK) on Terrien marginal degeneration (TMD). METHODS: Retrospective interventional case series. Medical records of 63 patients (71 eyes) who received LK for TMD at Qingdao Eye Hospital, Shandong Eye Institute from December 1995 to March 2014 were reviewed. A total of 56 eyes were treated with partial LK and 15 eyes with total LK. Complications, visual acuity recovery, and graft status were evaluated. RESULTS: Mean age of the patients was 50.4 ± 16.8 years. The follow-up period was 2.5 ± 0.9 years. The uncorrected distance visual acuity (UDVA) increased from preoperative 0.90 ± 0.44 logarithm of the minimum angle of resolution (logMAR) to 0.53 ± 0.27 logMAR at 1 year after surgery (t = 16.256, P < 0.001). The corrected distance visual acuity (CDVA) was 0.69 ± 0.30 logMAR preoperatively, and increased to postoperative 0.38 ± 0.22 logMAR (t = -19.982, P < 0.001). After surgery, mean astigmatism was 5.33 ± 2.44 diopters (D) compared with preoperative 10.19 ± 4.32 D (t = 7.351, P < 0.001), and the spherical equivalent decreased from preoperative -2.23 ± 2.34 D to -0.75 ± 2.04 D (t = -2.677, P = 0.012). There was a significant difference in UDVA, ΔUDVA, CDVA, ΔCDVA, and refractive astigmatism between the partial LK and total LK groups. The most common intraoperative complication was corneal perforation. The postoperative complications included double anterior chamber, persistent graft epithelium defects, corneal vascularization, immune rejection, graft ulcers, cataract, and recurrence of marginal degeneration. CONCLUSIONS: LK can effectively reduce refractive errors, improve visual acuity, and reduce the risk of corneal perforation for patients with TMD. The visual acuity after partial LK is superior to that after total LK.

Evaluation of an interlaced triple procedure: penetrating keratoplasty, extracapsular cataract extraction, and nonopen-sky intraocular lens implantation.

To evaluate an interlaced triple procedure that involved penetrating keratoplasty (PKP), extracapsular cataract extraction (ECCE) using diathermy capsulotomy, and nonopen-sky intraocular lens (IOL) implantation.This retrospective study involved data from 34 patients who were diagnosed with severe corneal opacities and cataracts. These patients were divided into an interlaced procedure group (21 patients) and a traditional procedure group (13 patients). In the interlaced group, the method of continuous curvilinear capsulorhexis (CCC) was completed via diathermy capsulotomy. The donor corneal button was sutured at 8 positions (at equal intervals) using 10-0 nylon sutures, and the IOL was inserted into the capsular bag using a closed anterior chamber approach at the 10:30 to 12 o'clock positions between the sutures. In the traditional group, CCC was completed using side-port capsular forceps, and the IOL was implanted using an open anterior chamber approach.In the interlaced group, the CCC, open-sky, and total operation times were significantly shorter than in the traditional group (P < .05). Neither the best-corrected visual acuity (BCVA) nor corneal endothelial cell density was significantly different between the groups at 1 and 6 months after the operation.This interlaced triple procedure for the treatment of corneal diseases with cataracts appears to be feasible and practical.

Long-term outcome of allogeneic cultivated limbal epithelial transplantation for symblepharon caused by severe ocular burns.

BACKGROUND: The therapeutic effects of allogeneic cultivated limbal epithelial transplantation (CLET) for symblephara at different degrees caused by ocular burns were evaluated in this study. METHODS: A series of interventional cases were involved in this retrospective study. Eighty eyes (80 patients) with symblephara underwent CLET and the success rates of surgical treatment as well as corneal conditions and risk factors for recurrent symblepharon were analyzed. RESULTS: The average age of patients was 32.4 ± 13.7 years (ranged from 4 to 60 years). The average follow-up time was 26.4 ± 13.6 months (ranged from 12 to 60 months). Symblepharon cases were caused by chemical burns (36 eyes) or thermal burns (44 eyes). The first surgical intervention achieved complete success in 40 eyes (50%), partial success in 25 eyes (31.3%), and failure in 15 eyes (18.8%). The rate of complete success was 85.0% in eyes with grade I/II symblephara, 51.5% in eyes with grade III eyes and 22.2% in eyes grade IV symblephara (P = 0.001). The treatment was completely successful in 23.1% of eyes with moderate or severe preoperative inflammatory action and 63.0% of eyes with mild or no inflammation (P = 0.000). The corneal conditions were improved in 43 eyes (53.8%), of which 21 eyes had improved visual acuity. The recurrence of symblepharon after the first CLET was positively correlated with symblepharon length (P = 0.003), preoperative inflammatory activity (P = 0.016) as well as postoperative cicatricial entropion and trichiasis (P = 0.038). CONCLUSIONS: CLET was effective on the recovery of anatomically deep fornixes in eyes caused by symblephara and corneal surface condition could be improved simultaneously. The success of surgical treatment was dependent on the effective control of inflammation and timely management of eyelid abnormalities.

Upregulation of NLRP3 inflammasome components in Mooren's ulcer.

PURPOSE: Mooren's ulcer (MU) is a peripheral corneal ulceration of presumed autoimmune etiology. NLRP3 inflammasome has been shown to be involved in a variety of autoimmune and auto-inflammatory diseases. However, the role of NLRP3 inflammasome in MU has not been investigated. Here, we evaluate the expression of NLRP3 inflammasome and its downstream inflammatory factors in human MU. METHODS: Conjunctival biopsy specimens were obtained from seven patients with MU and six healthy donors. The removed conjunctivas were histopathologically evaluated for NLRP3 inflammasome component expression using antibodies directed against NLRP3, Caspase-1 (CASP1), and Interleukin-1ß (IL-1ß). Quantitative real-time PCR was used to measure the mRNA expression of NLRP3 and IL-1ß, and the protein expressions of NLRP3, pro-CASP1, CASP1, and IL-1ß were detected by Western blotting. RESULTS: NLRP3 and IL-1ß mRNA expression showed higher levels in the MU group than in healthy controls. Western-blot and immunofluorescence analysis also showed that basal expression of NLRP3 inflammasome components (NLRP3, CAPS1, and IL-1ß) was elevated in patients with MU compared with healthy controls. Most importantly, we found that the cleavaged form of CASP1 and IL-1ß was significantly increased in MU patients compared with healthy donors, which indicates that the upregulation of NLRP3 inflammasome was probably responsible for the enhanced IL-1ß production in MU patients. CONCLUSIONS: This study demonstrated that the expression of the NLRP3-CASP1-IL-1ß signaling pathway was markedly increased in the conjunctival lesions of patients with MU, suggesting the involvement of NLRP3 inflammasome in the onset and development of the inflammation in MU.

Characteristics of immune rejection after allogeneic cultivated limbal epithelial transplantation.

PURPOSE: To investigate the characteristics and prognosis of immune rejection after allogeneic cultivated limbal epithelial transplantation (CLET). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Forty-two eyes of 41 patients undergoing allogeneic CLET for total limbal stem cell deficiency who completed a follow-up of at least 12 months. METHODS: Allogeneic cultivated limbal epithelial cells using human amniotic membrane as a carrier were transplanted into the recipient eye. Immune rejection occurred in 10 eyes; the medical records of these patients were reviewed. MAIN OUTCOME MEASURES: Best-corrected visual acuity, corneal opacification and neovascularization, immunofluorescence staining of CD4 and CD8 T cells, and distribution of Langerhans cells (LCs) in the corneal epithelium. RESULTS: The corneal epithelium became edematous with epithelial rejection lines and peripheral epithelial defects in 6 eyes. Circumlimbal vessels were hyperemic and extended up to the corneal stroma, thus resulting in aggravation of corneal neovascularization in 8 eyes. Corneal stromal opacification was observed in 9 eyes. CD4(+) or CD8(+) T cells were detected in 5 of 6 eyes from which impression cytology specimens were obtained. In vivo confocal microscopy examination revealed an accumulation of LCs in the central and peripheral corneal epithelium. All patients responded to antirejection therapy. One eye developed a second episode. CONCLUSIONS: The diagnosis of immune rejection after allogeneic CLET mainly depends on typical clinical manifestations. Delayed recognition can result in worsening corneal opacification and neovascularization. Reasonable use of topical immunosuppressives and a close follow-up within 6 months after allogeneic CLET are critical to improve the prognosis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of penetrating keratoplasty and deep lamellar keratoplasty for macular corneal dystrophy and risk factors of recurrence.

PURPOSE: To compare the therapeutic effects of penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) on patients with macular corneal dystrophy (MCD) and to analyze the risk factors of postoperative recurrence. DESIGN: Retrospective, interventional, comparative case series. PARTICIPANTS: Fifty-one patients (78 eyes) with MCD treated by PK or DALK at Shandong Eye Institute between January 1992 and December 2010. METHODS: The medical records of the patients were reviewed retrospectively. MAIN OUTCOME MEASURES: Best-corrected visual acuity, corneal endothelial density, complications, recurrence, graft survival, and risk factors for recurrence. RESULTS: Penetrating keratoplasty was performed in 57 eyes, and DALK was performed in 21 eyes. The mean follow-up time was 5.1±4.1 years (range, 1.0-18.0 years). The best-corrected visual acuity of the PK group was much better than that of the DALK group at 1, 2, 3, and 5 years. The corneal endothelial density was reduced to 1000 cells/mm2 or less within 5 years in 21.6% (11/51) of eyes treated by PK and in none of the eyes treated by DALK. The 1-year incidence rate of complications was 21.1% in the PK group, higher than the 4.8% rate in the DALK group. At the last visit, the rate of graft clarity was 87.7% and 85.7% in the 2 groups, respectively. Ten eyes (17.5%) treated by PK had recurrent MCD, with a rate of 0.8%, 7.7%, and 40% at 1, 5, and 10 years, respectively, whereas 9 eyes (42.9%) treated by DALK demonstrated recurrence, with a rate of 14.3% and 49.5% at 1 and 5 years, respectively. The recurrence risk was higher in patients whose age was 18 years or younger at onset or younger than 30 years at surgery. The recurrence risk after DALK was 5.066 times higher than that after PK. CONCLUSIONS: Penetrating keratoplasty more often immediately improves the visual acuity of patients with MCD, but many complications seem to be inevitable, especially continuous loss of corneal endothelium. Despite poor visual acuity and recurrence after surgery, DALK may produce fewer complications overall and more durable stability of the ocular surface compared with PK. The selection of PK or DALK for MCD should depend on the actual need and situation of certain patients. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Amniotic membrane traps and induces apoptosis of inflammatory cells in ocular surface chemical burn.

PURPOSE: Severe chemical burns can cause necrosis of ocular surface tissues following the infiltration of inflammatory cells. It has been shown that amniotic membrane transplantation (AMT) is an effective treatment for severe chemical burns, but the phenotypes of cells that infiltrate the amniotic membrane and the clinical significance of these cellular infiltrations have not previously been reported. The present work studies the inflammation cell traps and apoptosis inducing roles of the amniotic membrane after AMT in patients with acute chemical burns. METHODS: A total of 30 patients with acute alkaline burns were classified as having either moderate or severe burns. In all participants, AMT was performed within one week of his/her injury. After 7-9 days, the transplanted amniotic membranes were removed. Histopathological and immunohistochemical techniques were used for the examination and detection of infiltrating cells, and tests for the expression of CD (cluster of differentiation)15, CD68, CD3, CD20, CD57, CD31, CD147, and CD95 (Fas) were performed. A TUNEL (TdT-mediated dUTP nick end labeling) assay was used to confirm apoptosis of the infiltrating cells. Three patients with herpes simplex-induced keratitis who had undergone AMT to treat persistent epithelium defects were used as a control group. Amniotic membrane before transplantation was used as another control. RESULTS: After amniotic membrane transplantation, the number of infiltrating cells in patients with severe burns was significantly higher than in patients with moderate burns or in control patients (p<0.05). Among the severe burns patients, CD15 and CD68 were widely expressed in the infiltrating cells, and CD3, CD20, and CD57 were only found in a small number of cells. Occasionally, CD31-positive cells were found in the amniotic membranes. More cells that were CD147, Fas, and TUNEL positive were found in patients with severe burns than in patients with moderate burns or in control patients. CONCLUSIONS: Neutrophils and macrophages were the main cells that had infiltrated into the amniotic membrane during the acute phase of healing from a chemical burns. AMT can trap different inflammatory cells and induce apoptosis of inflammatory cells in acute ocular chemical burns.

Antifungal susceptibility for common pathogens of fungal keratitis in Shandong Province, China.

PURPOSE: To analyze common pathogens of fungal keratitis and results of antifungal drug sensitivity test in Shandong Province, China and provide guidance for appropriate choice of antifungal drugs in clinic. DESIGN: Retrospective, noncomparative study. METHODS: The pathogens isolated from 674 fungal keratitis patients between January 1, 2001 and December 31, 2006 were cultured and identified in Shandong Eye Institute, of which some common strains were tested for sensitivity to antifungal drugs. RESULTS: Fungi were positively cultured in 549 (81.5%) patients, in which the dominating pathogen was genus Fusarium (77.6%), with F. solani (37.3%), F. moniliforme (30.0%), and F. oxysporum (27.9%) being common species; Fusarium was mostly sensitive to natamycin, next to amphotericin B, and then to terbinafin. The second common pathogen was genus Aspergillus (10.8%), in which the main species were A. flavus (49.2%) and A. fumigatus (35.6%); Aspergillus was mostly sensitive to natamycin, next to terbinafin, and then to amphotericin B. Relatively, both Fusarium and Aspergillus were insensitive to ketoconazole, miconazole, itraconazole, fluconazole, and fluorocytosine. CONCLUSIONS: Fusarium is the most common pathogen of fungal keratitis, followed by Aspergillus, in Shandong Province, China. Natamycin is still the first choice in the treatment of hyphomycetic keratitis. Fusarium and Aspergillus are also sensitive to amphotericin B and terbinafin. Early diagnosis and treatments are vital to good prognosis in the treatment of fungal keratitis.

Primary diseases of corneal perforation in Shandong Province, China: a 10-year retrospective study.

PURPOSE: To analyze primary diseases of corneal perforation in Shandong Province, China. DESIGN: Retrospective, noncomparative study. METHODS: Medical records of 1,056 patients (1,080 eyes) with corneal perforation treated from January 1, 1997 through December 31, 2006 at Shandong Eye Institute were reviewed retrospectively, and primary diseases were evaluated. RESULTS: Corneal perforations mainly were caused by ocular trauma 715 eyes (66.8%) and infectious keratopathy 294 eyes (27.5%). In the traumatic eyes, corneal penetrating wound accounted for 608 eyes (85.0%), followed by explosion injury 42 eyes (5.9%), thermal burn 34 eyes (4.8%), and chemical injury 29 eyes (4.1%). In the infectious eyes, the most common pathogens were herpes simplex virus 124 eyes (42.2%), fungus 74 eyes (25.2%), and bacterium 20 eyes (6.8%). Repeated corneal perforation occurred in nine eyes, with primary diseases of herpes simplex keratitis (HSK; four eyes), Mooren ulcer (two eyes), necrotizing keratitis and scleratitis (one eye), bacterial keratitis (one eye), and alkali burn (one eye). Corneal grafts perforated in 31 eyes, resulting from recurrent HSK (eight eyes), implant autoproteolysis (seven eyes), bacterial infections (six eyes), recurrent Mooren ulcer (four eyes), immunologic rejection (three eyes), trauma (two eyes), and fungal recurrence (one eye). CONCLUSIONS: Ocular trauma and infectious keratopathy dominated among the primary diseases of corneal perforation in Shandong Province, China, during the past 10 years. HSK seems to be the most common cause of repeated corneal perforation. Recurrent primary diseases and implant autoproteolysis and infection more often result in graft perforation.

Hyphal growth patterns and recurrence of fungal keratitis after lamellar keratoplasty.

PURPOSE: To evaluate growth patterns of fungal pathogens in corneas and recurrence of fungal keratitis after lamellar keratoplasty (LK). DESIGN: Retrospective noncomparative study. PARTICIPANTS: One hundred seventy-four patients (174 eyes) with fungal keratitis who underwent LK at Shandong Eye Institute from January 2000 through November 2006. METHODS: Medical records of each patient were retrospectively reviewed. Hyphal growth patterns in corneas were evaluated by histopathological examination. Fungal recurrence after LK was observed during the follow-up. MAIN OUTCOME MEASURES: Pathogens, hyphal growth patterns, and postoperative fungal recurrence. RESULTS: The pathogens were Fusarium (85.1%), Aspergillus (6.3%), Alternaria (4.6%), Penicillium (2.3%), and Candida (1.7%). Most Fusarium hyphae (91.2%) lay parallel to the corneal stromal lamellae, whereas most Aspergillus (90.9%) grew vertically. Recurrence of fungal keratitis was found in 15 patients (8.6%) after LK, and the pathogens were F. oxysporum (33.3%), F. solani (26.7%), F. moniliforme (13.3%), Aspergillus flavus (13.3%), Aspergillus fumigatus (6.7%), and Aspergillus terreus (6.7%). In cases of fungal recurrence, the majority of hyphae (80%) grew vertically. There was a higher recurrence rate in patients with vertically growing hyphae (46.2%) than in those with horizontally growing hyphae (2%) (chi(2) = 54.664, P<0.001), as well as in those with Aspergillus keratitis (36.4%) versus those with Fusarium keratitis (7.4%) (chi(2) = 10.031, P = 0.002). Reproducibility of the fungal recurrence rate was moderate in the patients with different hyphal growth patterns (kappa = 0.534) but poor in those with different fungal pathogens (kappa = -0.044). CONCLUSIONS: Hyphal growth patterns in corneas differ not only in the same fungal genus but also in the same species. The fungal recurrence rate after LK in patients with hyphae growing horizontally is much lower than that in those with hyphae growing vertically. Growth patterns of fungal pathogens may be an important factor for fungal recurrence after LK.