Clinical and Morphological in Vivo Confocal Microscopy Findings following a Modified Biphasic Higher Fluence Transepithelial Corneal Crosslinking.

Purpose: To compare the refractive efficacy and morphological changes in the cornea following a novel biphasic higher fluence transepithelial corneal crosslinking (BI-TE-CXL) and transepithelial corneal crosslinking (TE-CXL) in adults keratoconus.Methods: Patients with progressive keratoconus who required corneal crosslinking were assigned to the BI-TE-CXL group (32 eyes, phase 1: 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro; phase 2: 3.6 J/cm2 for 6 min and 40 s of continuous light exposure at the front curvature apex with a 6 mm diameter light spot, UVX-2000, IROC) or the TE-CXL group (32 eyes, uniform 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal fluorescein staining (CFS), corneal topography, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM) were performed 3, 6, 12 and 24 months after surgery.Results: The CFS scores in the BI-TE-CXL group were significantly higher than those in the TE-CXL group on the first two days after surgery (p < 0.001). The Kmax (at 12 and 24 months) and CDVA (logMAR) were significantly lower in the BI-TE-CXL group than those in the TE-CXL group (p < 0.05). The corneal demarcation line under AS-OCT was visible in 81.3% of patients in the BI-TE-CXL group and 15.6% in the TE-CXL group. The depth of the demarcation line under IVCM was significantly deeper in the BI-TE-CXL group (248.3 ± 25.0 µm) than that of the TE-CXL group (136.5 ± 15.6 µm) in the central cornea (p < 0.001). The cross-linked collagen structures in the central cornea were still present after 12 months in the BI-TE-CXL group. No significant difference in sub-basal nerve density between the two groups (p > 0.05).Conclusions: Following BI-TE-CXL, CDVA was significantly improved, accompanied by deeper demarcation line depth and persistent crosslinked structures in the central corneal stroma.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye.

PURPOSE: To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. METHODS: Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC-DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. RESULTS: 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC-DE group were included. Compared with the NC, DE, and EKC-DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC-DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. CONCLUSIONS: Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

Meibomian Glands and Tear Film Findings in Type 2 Diabetic Patients: A Cross-Sectional Study.

Background: The characteristics of the meibomian gland and tear film in patients with type 2 diabetes (T2D) with different glycemic control levels and diabetic durations remain largely unexplored. This study aimed to identify the association of dry eye and meibomian gland dysfunction (MGD) in T2D. Materials and Methods: Ninety-nine patients with type 2 diabetes mellitus (DM group), 33 dry eye patients without diabetes mellitus (DE group), and 40 normal subjects (NC group) were recruited for this study. Participants were evaluated with an Ocular Surface Disease Index (OSDI) questionnaire, tear film breakup time (BUT), the Schirmer I test (SIT), corneal fluorescein staining (FL), lipid layer thickness (LLT), and MGD parameters. Glycosylated hemoglobin (HbA1c ) and duration of diabetes were recorded. Results: The SIT value in the DM group was higher than that of the DE group (p < 0.05). The BUT and LLT were lower, and MGD parameters were higher in the DM group than those of the DE and NC groups (p < 0.05). In the DM group, 47 patients were diagnosed with dry eye (DM + DE group), whereas 40 patients without dry eye were categorized as the DM - DE group. The SIT, BUT, and LLT values in the DM - DE group were higher (p < 0.01), and MGD parameters were lower (p < 0.01) in the DM - DE group than those of the DM + DE group. The MGD parameters were higher in the DM - DE group than those in the NC group (p < 0.05). The HbA1c levels were correlated with OSDI, BUT, LLT, FL, and MGD parameters (p < 0.001) in the DM group. However, in patients with low HbA1c , normal SIT value, and low OSDI, the MGD parameters were higher than those in the NC group (p < 0.05). The duration of diabetes positively correlated with MGD parameters (p < 0.001). Conclusion: Asymptomatic MGD may be an early sign of dry eye and ocular discomfort in T2D. The MGD parameters were associated with the HbA1c level and diabetic duration.

Safety and efficacy of repeated crosslinking assisted by transepithelial double-cycle iontophoresis in keratoconus progression after primary corneal crosslinking.

OBJECTIVES: To evaluate the safety and efficacy of repeated corneal collagen crosslinking assisted by transepithelial double-cycle iontophoresis (DI-CXL) in the management of keratoconus progression after primary CXL. METHODS: A retrospective analysis was conducted in the patients who underwent repeated CXL between 2016 and 2018. These patients were treated with DI-CXL if keratoconus progression was confirmed after primary CXL. Scoring of ocular pain and corneal epithelial damage, visual acuity, corneal tomography, in vivo corneal confocal microscopy (IVCM) was performed before and at 3, 6, 12, and 24 months after DI-CXL. RESULTS: Overall, 21 eyes of 12 patients (mean age 17.3 ± 1.9 years) were included in this study. Before DI-CXL, an average increase of 4.26 D in Kmax was detected in these patients with a mean follow-up interval of (23.0 ± 13.7) months. After DI-CXL, corneal epithelial damage rapidly recovered within days. Visual acuity remained unchanged with follow-up of 24 months. When compared to baseline, significant decreases were observed in Kmax (at 3 months) and K2 (at 3 and 6 months) after DI-CXL. Corneal thickness of thinnest point significantly decreased at 3 months postoperatively. When compared to baseline, no significant differences were found in any of the refractive or tomographic parameters at 12 and 24 months. IVCM revealed trabecular patterned hyperdense tissues after DI-CXL in the anterior stroma at the depth of 200 µm or more. No corneal infiltration or persistent epithelial defect was recorded after DI-CXL. CONCLUSION: DI-CXL is safe and effective as a good alternative in stabilizing keratoconus progression after primary CXL.

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis.

PURPOSE: The aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus. METHODS: A retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively. RESULTS: Sixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and Kmax significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, Kmax was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) µm after C-CXL, and at (251.2 ± 28.1) µm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups. CONCLUSION: EI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol.

Meibomian Gland Dysfunction Correlates to the Tear Film Instability and Ocular Discomfort in Patients with Pterygium.

Pterygium is a very common disease in an eye clinic characterized by a benign proliferation of local conjunctiva that often crosses the limber of cornea and extends into corneal surface. Variety of studies has showed that pterygium is able to result in ocular discomfort and the change of ocular surface environment, such as dry eye. However, the link between abnormal tear film function and pterygium is controversial. Meibomian gland dysfunction (MGD) is a common cause of dry eye and ocular discomfort but is often neglected, which may be the missing link between dry eye and pterygium. In this study, our data firstly revealed increased abnormality of meibomian gland structure and function in pterygium patients, representing with increased abnormality of MGD parameters such as meibum expression (P < 0.001) and meibomian gland loss (P < 0.001). Besides, the scores of MGD severity in patients with progressive pterygium were higher than those in patients with resting pterygium. The correlation between MGD parameters and ocular discomfort as well as dry eye indexes is also established. These findings suggest that MGD correlates to the tear film instability and ocular discomfort in patients with pterygium.

[Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: one year results].

OBJECTIVE: To evaluate the early clinical results of keratoconic eyes treated with transepithelial iontophoresis corneal collagen cross-linking (i-CXL) within 1 year. METHODS: Propective nonrandomized study. Twenty-three eyes of 23 patients with progressive keratoconus with minimum corneal thickness from 380 µm to 420 µm (including the epithelium) were included in this prospective, nonrandomized clinical study and treated with i-CXL. Scoring of pain and foreign body sensation, slit lamp examination, uncorrected visual acuity (UCVA) and best corrected distance visual acuity (BCVA), corneal topography, anterior segment optical coherence tomography (AS-OCT), in vivo corneal confocal microscopy and endothelial cell count were assessed before surgery and at 1, 3, 6 and 12 months (m) postoperatively. Paired t test was applied for statistical analysis. RESULTS: Moderate pain and foreign body sensation were reported by most patients on postoperative Day (D) 1, but rapidly decreased and eventually disappeared on D3. Mild epithelial damage was observed on D1, and the epithelium fully recovered on D3. Improvement of UCVA and BCVA were recorded at 3 months and 12 months postoperatively. Orbscan II corneal topography revealed the significant reductions of Kmax and Kmin from 3m to 12m (Kmax, t = 2.912, P < 0.01, Kmin, t = 2.508, P < 0.05) postoperatively while the other parameters remained stable. The Kmax and Kmin at 12m was (52.94 ± 4.87) and (46.78 ± 3.71) respectively, while the preoperative values was (54.37 ± 5.56) and (48.53 ± 3.57) respectively. Within 1m postoperatively, AS-OCT exhibited an increase of reflectance with a white line (demarcation line) in the anterior stroma, in vivo confocal microscopy also showed the significant thickening and increased connections of collagen fibers with maximal depth of about 133 µm. The corneal endothelial cell density remained stable (t = 0.915, P > 0.05). None of the patients showed postoperative complications such as corneal infection, scarring, ulcer, persistent epithelial defect, etc. CONCLUSIONS: Priliminary clinical results within 1 year postoperatively demonstrated the efficacy and safety of i-CXL for the management of progressive keratoconus. This technique was applicable for keratoconic eyes with minimum corneal thickness around 400 µm. i-CXL showed the advantage of short time consuming in surgery, rapid recovery and few complication, and has the potential to become a valid alternative for the treatment of keratoconus.

[The clinical study of corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas].

OBJECTIVE: To evaluate the clinical results of keratoconic eyes with thin corneas that were treated by using corneal collagen cross-linking with hypo-osmolar riboflavin solution. METHODS: Retrospective, nonrandomized study. Fifteen eyes of 15 patients with progressive keratoconus and corneal thickness of less than 400 µm (without the epithelium) were included in this study. Application of hypo-osmolar riboflavin solution to the cornea for 30 minutes after its de-epithelialization was followed by ultraviolet A collagen cross-linking. Corneal thickness was measured with anterior segment OCT before surgery, after epithelial removal, and after hypotonic riboflavin solution application. Before the ultraviolet A application was started, we must be sure that the thinnest cornea was equal to or greater than 400 µm. Examinations comprised an evaluation of uncorrected distance visual acuity and best corrected visual acuity, slit-lamp microscopy, corneal topography, and endothelial cell counting after the procedure. RESULTS: Before surgery, the mean corneal thickness (with the epithelium) was (399.27 ± 17.87) µm, and after the removal of epithelium, the thickness of the cornea was reduced to (354.00 ± 18.57) µm. After the application of the hypo-osmolar riboflavin solution, this value increased to (477.73 ± 20.87) µm. The improvements in visual acuity and keratometry readings occurred during the follow-up. No statistically signiflcant differences were found between preoperative and postoperative endothelial cell counts. No complications such as scarring lesions in the stroma and corneal endothelial damage were observed throughout the study period. CONCLUSIONS: The results of our study, using hypo-osmolar riboflavin solution in a cross-linking procedure in thin corneas, show a stability of keratoconus 12 months after cross-linking.

Differential expression and function of survivin during the progress of pterygium.

PURPOSE: To investigate the expression pattern and function of survivin in the development of pterygium. METHODS: Primary pterygia at quiescent or advanced clinical stage and normal human conjunctival tissues were used in this study. Pterygium epithelial cells (PECs) were cultured in keratinocyte serum-free defined medium and harvested at different growth stages. Tissue sections and cultured cells were detected with survivin, phosphorylated survivin (Thr43), p63, p57, and p21 on protein, and/or mRNA level. Cell Counting Kit (CCK)-8 assay was performed to measure proliferation status of primary cultured PECs. Small interfering (si) RNA specific for survivin was transfected on PECs at subconfluence stage. RESULTS: Survivin was highly expressed in all pterygium tissues, but not in normal human conjunctiva, at mRNA and protein levels. It was mainly present in the epithelial cytoplasm of pterygium at quiescent stage, while present in the nucleus of pterygium at advanced stage. Phosphorylated survivin was upregulated in pterygium at advanced stage. Pterygium epithelial cells cultured under subconfluence stage showed higher expression of survivin and p63, but lower expression of p57 and p21, compared with PECs reached confluence. Both total and phosphorylated survivin was mainly expressed in the nuclei of PECs under subconfluence, and there was cytoplasmic translocation of survivin when PECs reached confluence. The knockdown of survivin by siRNA inhibited proliferation of PECs, accompanied by downregulation of p63, and upregulation of p57 and p21. CONCLUSIONS: Higher subcellular expression and phosphorylation of survivin may play roles in the development of pterygium. Survivin could be targeted for the treatment of pterygium.

Meibomian gland dysfunction determines the severity of the dry eye conditions in visual display terminal workers.

OBJECTIVE: To explore meibomian gland dysfunction (MGD) may determine the severity of dry eye conditions in visual display terminal (VDT) workers. METHODOLOGY: Prospective, case-control study carried out in China.106 eyes of 53 patients (VDT work time >4 hour per day) were recruited as the Long time VDT group; 80 eyes of 40 control subjects (VDT work time ≤ 4 hour per day) served as the Short time VDT group. A questionnaire of Ocular Surface Disease Index (OSDI) and multiple tests were performed. Three dry eye tests: tear film breakup time (BUT), corneal fluorescein staining, Schirmer I test; and three MGD parameters: lid margin abnormality score, meibum expression assessment (meibum score), and meibomian gland dropout degree (meiboscore) using Keratograph 5 M. PRINCIPAL FINDINGS: OSDI and corneal fluorescein score were significantly higher while BUT was dramatically shorter in the long time VDT group than the short time VDT group. However, the average of Schirmer tear volumes was in normal ranges in both groups. Interestingly, the three MGD parameters were significantly higher in the long time VDT group than the short time one (P<0.0001). When 52 eyes with Schirmer <10 mm and 54 eyes with Schirmer ≥ 10 mm were separated from the long time VDT workers, no significant differences were found between the two subgroups in OSDI, fluorescein staining and BUT, as well as the three MGD parameters. All three MGD parameters were positively correlated with VDT working time (P<0.0001) and fluorescein scores (P<0.0001), inversely correlated with BUT (P<0.05), but not correlated with Schirmer tear volumes in the VDT workers. CONCLUSIONS: Our findings suggest that a malfunction of meibomian glands is associated with dry eye patients in long term VDT workers with higher OSDI scores whereas some of those patients presenting a normal tear volume.

[Corneal collagen crosslinking in the treatment of infectious keratitis].

OBJECTIVE: To investigate the feasibility and clinical efficacy of corneal collagen crosslinking (CXL) for the treatment of infectious keratitis. METHODS: Noncomparative interventional case series.19 patients with infectious keratitis admitted to our hospital between November 2011 and January 2012 were recruited into this study, CXL was performed when medications combined proved poor therapeutic effects. Postoperatively, the graft status, graft clarity, the visual prognosis and postoperative complications were recorded. RESULTS: In 15 cases, there was improvement in symptoms one week after operation.3 cases remained stable, while 1 case reported deteriorated function at the same time.One month after operation, Corneal melting was arrested and complete epithelialization was achieved in 13 cases, 5 cases experienced significant improvement and 1 patient experienced corneal ulcer perforation.2 month after surgery, patients with healed corneal ulcer increased to 17 cases, and 2 cases experienced corneal ulcer perforation. Those 17 cases with healed corneal ulcer were followed up for 6 months, 15 cases had significant improvement in best-corrected visual acuity, 2 cases had no significant change, and no relapse was observed in those 17 cases. CONCLUSION: Our experience based on the above and other cases suggest that CXL could be an effective tool in battling difficult cases of infectious keratitis. This treatment could present many advantages but will need further investigation both by in vitro and in vivo studies.