Intravenous glucocorticoids therapy in the treatment of Graves' ophthalmopathy: a systematic review and Meta-analysis.

AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids (IVGC) as first-line treatment for Graves' ophthalmopathy (GO). METHODS: A systematic review and Meta-analysis of randomized clinical trials (RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score (CAS), and adverse events. RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence (one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio (RR) 7.50, 95% confidence interval (CI) 1.14 to 49.26]. Moderate quality evidence (four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids (OGC), with of RR being 1.51 (95%CI 1.25 to 1.83). There was low quality evidence (one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response (RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using rituximab (RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil (MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF (RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence (one trial) showed that participants with dysthyroid optic neuropathy (DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression (RR 3.33, 95%CI 0.51 to 21.89). CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy.

AIMS: To examine possible benefits of intravitreal anti-vascular endothelial growth factor (VEGF) agent treatment immediately after cataract surgery for patients with diabetic retinopathy (DR). METHODS: A comprehensive literature search was performed using the Cochrane collaboration methodology to identify randomized controlled trials (RCTs) and comparative studies of cataract surgery with or without anti-VEGF agent treatment for any diabetic retinopathy. Meta-analyses were performed for clinical outcome parameters including changes in macular thickness (MT), best-corrected visual acuity (BCVA), incidence of diabetic retinopathy and maculopathy progression, laser treatment rate, and other complications. RESULTS: Nine RCTs and 3 nonrandomized comparative studies were identified and used for comparing cataract surgery with intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) treatment (338 eyes, intervention group) to cataract surgery alone (329 eyes, control group). Analysis of all data showed that the mean BCVA at 1 week postoperatively had no statistically significant difference in the two groups, but at 1, 3, and 6 months postoperatively, the mean BCVA was statistically significantly better in the anti-VEGF treatment group than that in cataract surgery alone group. Analysis of all data showed that the mean MT was statistically significantly less in the anti-VEGF treatment group at 1 week and 1, 3, and 6 months postoperatively (P=0.05, P=0.006, P=0.0001, and P=0.0001, respectively); but postoperative clinical outcomes were differentiated from the type of anti-VEGF agents, IVB or IVR, and the existing macular edema preoperatively. Intravitreal anti-VEGF agent treatment statistically significantly reduced the incidence of diabetic retinopathy progression and maculopathy progression compared to the control group (P=0.0003, P < 0.00001, respectively). CONCLUSION: IVB or IVR treatment immediately after cataract surgery may represent a safe and effective strategy to prevent postoperative macular thickening or reduce macular edema and result in greater mean improvements in visual acuity for diabetic patients.

Bandage Contact Lens Application Reduces Fibrotic Wound Healing of Flap Margins after FS-LASIK: A Prospective Randomized Clinical Trial.

PURPOSE: To assess the efficacy of applying bandage contact lens (BCL) in reducing the fibrotic healing response of flap margins following femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: In this prospective, randomized, interventional, observer-masked trial, 41 patients (82 eyes) with myopia and/or myopic astigmatism were scheduled to undergo FS-LASIK. After surgery, patients were fitted with a BCL in one eye (BCL eyes, n=41) but not in the contralateral eye (control eyes, n=41), following randomized allocation of the BCL to the left or right eye of each patient. The BCL was left in place overnight and removed the following morning. All eyes subsequently received standardized postoperative treatments. Patients were followed up for 6 months. We evaluated patients' self-reported postoperative symptom scores for pain, photophobia, tearing, and foreign-body sensation. At 6 months after surgery, we examined the corneal flap margin and adjacent regions, and photographed them using slit-lamp biomicroscopy, to subjectively evaluate the wound healing response. RESULTS: Postoperative pain and photophobia were milder in the BCL group than in the control group (P=0.041 and P=0.003, respectively), but patients felt more foreign-body sensation in the eye with a BCL than in the control eye (P=0.001). There was no significant difference in tearing score between BCL eyes and control eyes (P=0.118). Regarding the fibrotic healing response of the flap margin, control eyes showed a wide, bright peripheral circumferential band with a spiculated edge and high reflectivity; conversely, BCL eyes showed a markedly narrower and smoother peripheral circumferential band, with a less spiculated edge and lower reflectivity (P < 0.001). CONCLUSION: Patients felt less discomfort in eyes treated with a BCL after FS-LASIK than in control eyes. BCL-treated eyes also had a less intense wound healing response at the flap margins than control eyes in some of patients. BCLs may merit consideration as a treatment option after FS-LASIK for special patients. This trial is registered with ChiCTR1800016579.

Laser-Assisted Subepithelial Keratectomy versus Laser In Situ Keratomileusis in Myopia: A Systematic Review and Meta-Analysis.

This systematic review was to compare the clinical outcomes between laser-assisted subepithelial keratectomy (LASEK) and laser in situ keratomileusis (LASIK) for myopia. Primary parameters included mean manifest refraction spherical equivalent (MRSE), MRSE within ±0.50 diopters, uncorrected visual acuity (UCVA) ≥20/20, and loss of ≥1 line of best-corrected visual acuity (BCVA). Secondary parameters included flap complications and corneal haze. Twelve clinical controlled trials were identified and used for comparing LASEK (780 eyes) to LASIK (915 eyes). There were no significant differences in visual and refractive outcomes between the two surgeries for low to moderate myopia. The incidence of loss of ≥1 line of BCVA was significantly higher in moderate to high myopia treated by LASEK than LASIK in the mid-term and long-term followup. The efficacy (MRSE and UCVA) of LASEK appeared to be a significant worsening trend in the long-term followup. Corneal haze was more severe in moderate to high myopia treated by LASEK than LASIK in the mid-term and long-term followup. The flap-related complications still occurred in LASIK, but the incidence was not significantly higher than that in LASEK. LASEK and LASIK were safe and effective for low to moderate myopia. The advantage of LASEK was the absence of flap-related complications, and such procedure complication may occur in LASIK and affect the visual results. The increased incidence of stromal haze and regression in LASEK significantly affected the visual and refractive results for high myopia.

Excimer laser phototherapeutic keratectomy for the treatment of clinically presumed fungal keratitis.

This retrospective study was to evaluate treatment outcomes of excimer laser phototherapeutic keratectomy (PTK) for clinically presumed fungal keratitis. Forty-seven eyes of 47 consecutive patients underwent manual superficial debridement and PTK. All corneal lesions were located in the anterior stroma and were resistant to medication therapy for at least one week. Data were collected by a retrospective chart review with at least six months of follow-up data available. After PTK, infected corneal lesions were completely removed and the clinical symptoms resolved in 41 cases (87.2%). The mean ablation depth was 114.39 ± 45.51 µ m and diameter of ablation was 4.06 ± 1.07 mm. The mean time for healing of the epithelial defect was 8.8 ± 5.6 days. Thirty-four eyes (82.9%) showed an improvement in best spectacle-corrected visual acuity of two or more lines. PTK complications included mild to moderate corneal haze, hyperopic shift, irregular astigmatism, and thinning cornea. Six eyes (12.8%) still showed progressed infection, and conjunctival flap covering, amniotic membrane transplantation, or penetrating keratoplasty were given. PTK is a valuable therapeutic alternative for superficial infectious keratitis. It can effectively eradicate lesions, hasten reepithelialization, and restore and preserve useful visual function. However, the selection of surgery candidates should be conducted carefully.

The effect of multivitamin/mineral supplements on age-related cataracts: a systematic review and meta-analysis.

Antioxidant vitamins supplements have been suggested as a strategy to decrease the risk of age-related cataract development. However, the results from observational studies and interventional trials of associations between antioxidant vitamins A, C, and E and cataract development have been inconsistent. We aim to evaluate the effectiveness of multivitamin/mineral supplements for decreasing the risk of age-related cataracts by conducting a systematic review and meta-analysis. In September 2013, we searched multiple databases to identify relevant studies including both cohort studies and randomized controlled trials (RCTs). A random-effects model was used to calculate the pooled relative risks (RR) with a 95% confidence interval (CI). Twelve prospective cohort studies and two RCTs were included. Pooled results from the cohort studies indicated that multivitamin/mineral supplements have a significant beneficial effect in decreasing the risk of nuclear cataracts (RR: 0.73; 95% CI: 0.64-0.82), cortical cataracts (RR: 0.81; 95% CI: 0.68-0.94), and any cataracts (RR: 0.66; 95% CI: 0.39-0.93). In addition, there were no decreases in the risk of posterior capsular cataracts (RR: 0.96; 95% CI: 0.72-1.20) or cataract surgery (RR: 1.00; 95% CI: 0.92-1.08). The two RCTs demonstrated that multivitamin/mineral supplements could decrease the risk of nuclear cataracts. There is sufficient evidence to support the role of dietary multivitamin/mineral supplements for the decreasing the risk of age-related cataracts.

Topical anesthesia versus regional anesthesia for cataract surgery: a meta-analysis of randomized controlled trials.

PURPOSE: To examine possible differences in the clinical outcomes of topical anesthesia (TA) and regional anesthesia including retrobulbar anesthesia (RBA) and peribulbar anesthesia (PBA) in phacoemulsification. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients from previously published randomized controlled trials (RCTs) of phacoemulsification under TA and RBA/PBA reporting clinical outcomes. METHODS: A comprehensive literature search was performed according to the Cochrane Collaboration method to identify RCTs that compare TA and RBA/PBA in phacoemulsification. MAIN OUTCOME MEASURES: Primary outcome parameters investigated were pain score during and after surgery, intraoperative difficulties and inadvertent ocular movement, intraoperative necessity to administer additional anesthesia, and patient preference. Secondary outcome parameters investigated were postoperative visual acuity, anesthesia-related complications, intraoperative complications, and severe local or systemic complications. RESULTS: Fifteen studies were identified and analyzed to compare TA (1084 eyes) with RBA/PBA (1121 eyes) in phacoemulsification. Data synthesis showed that intraoperative and postoperative pain perception was significantly higher in the TA group (P < 0.05). The TA group showed more frequent inadvertent ocular movement (P < 0.05) and a greater intraoperative need for supplementary anesthesia (P = 0.03). There was no statistically significant difference between the 2 groups in intraoperative difficulties as assessed by the surgeons (P > 0.05). Patients significantly preferred TA (P < 0.00001). The RBA/PBA group had more frequent anesthesia-related complications, such as chemosis, periorbital hematoma, and subconjunctival hemorrhage (P < 0.05). There was no statistically significant difference in surgery-related complications (P > 0.05). CONCLUSIONS: Compared with RBA/PBA, TA does not provide the same excellent pain relief in cataract surgery; however, it achieves similar surgical outcomes. Topical anesthesia reduces injection-related complications and alleviates patients' fear of injection. The choice of TA is not suitable for patients with a higher initial blood pressure or greater pain perception.

Contrast sensitivity after zyoptix tissue saving LASIK and standard LASIK for myopia with 6-month followup.

This control-matched comparative study evaluated changes in contrast sensitivity after Zyoptix tissue-saving (TS) LASIK and Planoscan standard LASIK (Technolas 217z, Bausch & Lomb) for myopia 6 months postoperatively. 102 TS LASIK-treated eyes were matched with 102 standard LASIK-treated eyes (divided into low, moderate, and high groups). There were no significant differences in refraction outcomes between the groups postoperatively. In high group, a significant reduction in contrast sensitivity after TS LASIK was found at high spatial frequencies (P < .05) under photopic conditions and at middle to high spatial frequencies (P < .05) under mesopic conditions. And significant reduction was also found in standard LASIK at high spatial frequency (P < .05) under mesopic conditions. The reduction was significantly lower in TS LASIK than that in standard LASIK at high spatial frequencies (P < .05) under mesopic conditions. TS LASIK was prone to reduce mesopic contrast sensitivity of high myopia at high spatial frequencies.

A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy.

AIMS: To examine possible benefits of intravitreal bevacizumab (IVB) pretreatment in vitrectomy for severe diabetic retinopathy. METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify randomised controlled trials and comparative studies of vitrectomy with or without IVB pretreatment for severe or complicated diabetic retinopathy. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal tears and mean surgical time) and postoperative outcome parameters (including best-corrected visual acuity, recurrent vitreous haemorrhage, reabsorption time of blood and other complications). RESULTS: Six randomised controlled trials and one comparative study were identified and used for comparing vitrectomy alone (142 eyes, control group) with vitrectomy with IVB pretreatment (139 eyes). The intraoperative findings showed that the incidence of intraoperative bleeding and frequency of endodiathermy were statistically significantly less in the IVB pretreatment group (p<0.01) than in the vitrectomy alone group. The IVB pretreatment group took significantly less surgical time than the control group (p=0.003). Postoperative results indicated that reabsorption time of blood was significantly shorter (p=0.04), incidence of recurrent VH was almost significantly less (p=0.05), and final best-corrected visual acuity was significantly better (p=0.003) in the IVB group than in the control group. Other complications, including final retinal detachment, and reoperation, were statistically insignificant. CONCLUSION: IVB pretreatment in vitrectomy can achieve excellent clinical outcomes for severe diabetic retinopathy. It potentially facilitates surgeons' manoeuvres and reduces intra- and postoperative complications.

Meta-analysis: clinical outcomes of laser-assisted subepithelial keratectomy and photorefractive keratectomy in myopia.

PURPOSE: To examine possible differences in clinical outcomes between laser-assisted subepithelial keratectomy (LASEK) and photorefractive keratectomy (PRK) for myopia. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients from previously reported randomized controlled trials (RCTs) and comparative studies of LASEK and PRK with clinical outcomes. METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify RCTs and comparative studies comparing LASEK and PRK for myopia. MAIN OUTCOME MEASURES: Primary outcome parameters included uncorrected visual acuity (UCVA) of 20/20 or better, manifest refractive spherical equivalent (SE) within ± 0.50 diopters (D), final refractive SE, and final UCVA of 20/40 or worse. Secondary outcome parameters included healing time of corneal epithelium, postoperative pain, and corneal haze. RESULTS: Twelve studies were identified and used for comparing PRK (499 eyes) with LASEK (512 eyes) for myopia. There were no significant differences in odds ratio (OR), weighted mean difference (WMD), and standardized mean difference (SMD) in the primary and secondary outcome measures. The final mean refractive SE (WMD, 0.00; 95% confidence interval [CI], -0.08 to 0.07; P = 0.95), manifest refractive SE within ± 0.50 D of the target (OR, 0.90; 95% CI, 0.63-1.29; P = 0.56), patients achieving UCVA of 20/20 or better (OR, 0.86; 95% CI, 0.61-1.20; P = 0.37), final UCVA of 20/40 or worse (OR, 1.26; 95% CI, 0.63-2.51; P = 0.52), re-epithelialization time (WMD, 0.08; 95% CI, -0.44 to 0.59; P = 0.77), and postoperative pain (SMD, 0.26; 95% CI, -0.20 to 0.72; P = 0.27) were analyzed. However, LASEK-treated eyes showed less corneal haze at 1 month after surgery (WMD, 0.25; 95% CI, 0.10-0.39; P = 0.0007) and 3 months after surgery (WMD, 0.14; 95% CI, 0.01-0.26; P = 0.03) compared with PRK. No statistically significant difference was observed between the 2 groups at 6 months after surgery (WMD, 0.14; 95% CI, -0.02 to 0.30; P = 0.08). CONCLUSIONS: In this meta-analysis, LASEK-treated eyes had no significant benefits over PRK-treated ones with regard to clinical outcomes. Less corneal haze was observed in LASEK-treated eyes at 1 to 3 months after surgery.

The expression of intercellular adhesion molecule-1 induced by CD40-CD40L ligand signaling in orbital fibroblasts in patients with Graves' ophthalmopathy.

PURPOSE: The aim of the present study was to examine the effect of CD40 ligand (CD40L) on intercellular adhesion molecule-1 (ICAM-1) production and involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) signaling pathways by CD40-CD40L ligand in orbital fibroblasts (OFs) in patients with Graves' ophthalmopathy (GO). METHODS: OFs were stimulated with soluble CD40L, and conditioned media and lysed cells were subjected to Western blot and real-time quantitative polymerase chain reaction analyses. Inhibitors specific to various signal transduction pathways were used to determine the signal pathways involved. RESULTS: ICAM-1 protein and mRNA in OFs of GO groups were upregulated by CD40L compared with those in normal OFs. Treatment of OFs with CD40L increased ICAM-1 mRNA levels in a dose- and time-dependent manner. CD40L induced the phosphorylation of p38 MAPK, extracellular-regulated kinase1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and IkappaB and the activation of NF-kappaB. Inhibition of the ERK1/2, p38, JNK, and NF-kappaB pathways blocked CD40L-induced ICAM-1 secretion. Furthermore, the activation of NF-kappaB was significantly affected by ERK1/2 and JNK inhibitors, but not by p38. OF ICAM-1 expression was predominantly p38 MAPK and NF-kappaB dependent. ERK1/2 and JNK were implicated in the NF-kappaB pathway. Analyses of ICAM-1 mRNA synthesis revealed that CD40L-induced ICAM-1 expression was mediated by multiple factors. CONCLUSIONS: CD40L can potently induce ICAM-1 expression in OF cells through multiple signal pathways. The p38 MAPKs and NF-kappaB pathways may play an important permissive role in CD40L-induced ICAM-1 expression in OFs.

Effect of intraoperative mitomycin-C on healthy corneal endothelium after laser-assisted subepithelial keratectomy.

PURPOSE: To evaluate the effect of mitomycin-C (MMC) on corneal endothelial cells after laser-assisted subepithelial keratectomy (LASEK). SETTING: Department of Ophthalmology, Changzheng Hospital, Shanghai, China. METHODS: One hundred seventy-four eyes of 89 patients who did not previously wear contact lenses were treated with LASEK with intraoperative use of topical MMC 0.02% (15 seconds). Noncontact corneal specular microscopy was performed in all eyes preoperatively and 1, 3, and 6 months after surgery. Preoperative pachymetry and ablation depth were measured in all eyes. Repeated-measures analysis of variance was used to compare the changes in the endothelial central cell density (CCD), coefficient of variation in cell size (CV), and percentage of hexagram cells (HEX) over time. Linear regression analysis was conducted to analyze the correlation between the change in the 3 corneal endothelium indices over time and the ablation depth and residual stroma bed (RSB) thickness. RESULTS: Preoperatively, the mean CCD was 2755 cells/mm(2)+/-373 (SD), the mean CV was 31.45+/-8.26, and the mean HEX was 66.03%+/-25.83%. After LASEK, there were no statistically significant changes in CCD, CV, or HEX (P>.05). Multiple linear regression did not identify ablation depth or RSB thickness as being predictive of a change in CCD, CV, or HEX (P>.05). CONCLUSION: The use of intraoperative topical MMC 0.02% for 15 seconds after LASEK did not affect the corneal endothelium.