Alex L. K. Ng

Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models

Curcumin is a polyphenolic diketone from turmeric. Because of its anti-oxidant and anti-inflammatory effects, it was tested in animal models of Alzheimers disease, reducing levels of amyloid and oxidized proteins and preventing cognitive deficits. An alternative mechanism of these effects is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Metals can induce Abeta aggregation and toxicity, and are concentrated in AD brain. Chelators desferrioxamine and clioquinol have exhibited anti-AD effects. Using spectrophotometry, we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+ showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at least two curcumin molecules. The interaction of curcumin with copper reached half-maximum at approximately 3-12 microM copper and exhibited positive cooperativity, with Kd1 approximately 10-60 microM and Kd2 approximately 1.3 microM (for binding of the first and second curcumin molecules, respectively). Curcumin-iron interaction reached half-maximum at approximately 2.5-5 microM iron and exhibited negative cooperativity, with Kd1 approximately 0.5-1.6 microM and Kd2 approximately 50-100 microM. Curcumin and its metabolites can attain these levels in vivo, suggesting physiological relevance. Since curcumin more readily binds the redox-active metals iron and copper than redox-inactive zinc, curcumin might exert a net protective effect against Abeta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB.

Conventional versus accelerated corneal collagen cross‐linking in the treatment of keratoconus

Background This study aims to compare the effect of conventional corneal collagen cross-linking (CXL) with accelerated corneal collagen cross-linking in treatment of keratoconus. Design A comparative interventional study was employed. Participants Participants were consecutive cases of progressive keratoconus receiving either conventional (3 mW/cm2 irradiance for 30 min) or accelerated CXL (9 mW/cm2 irradiance for 10 min). Methods Clinical and topographic parameters were compared between the two groups. Postoperative corneal stromal demarcation line was measured using anterior segment optical coherence tomography. Main Outcome Measures Clinical and topographic parameters such as corrected distant visual acuity (CDVA), maximum keratometry (Kmax), mean keratometry (Kmean), demarcation line depth were gathered from medical records. Results There were a total of 26 eyes with an average follow up of 13.9 ± 6.3 months. Fourteen eyes received conventional CXL, and 12 eyes had accelerated CXL. In the conventional CXL group, CDVA improved significantly (P = 0.021). There was also a significant reduction in Kmax (P = 0.003) and Kmean (P = 0.002). In the accelerated CXL group, no significant changes were found in CDVA (P = 0.395), Kmax (P = 0.388) and Kmean (P = 0.952) postoperatively. A significantly greater reduction in Kmax and Kmean were seen in conventional CXL compared to its accelerated counterpart (P = 0.001 and 0.015, respectively). The demarcation line was deeper in eyes with conventional CXL (P = 0.013), and the depth correlated significantly with the change in Kmean (r = −0.432, P = 0.045). Conclusion Conventional and accelerated CXL are effective in stabilizing keratoconus progression after a mean of 12 months. Patients undergoing conventional CXL showed clinical improvement with greater corneal flattening, which correlated with a deeper corneal stromal demarcation line. This current study is the first to report such correlation.This study aims to compare the effect of conventional corneal collagen cross‐linking (CXL) with accelerated corneal collagen cross‐linking in treatment of keratoconus.

Vector analysis of astigmatic correction after small-incision lenticule extraction and femtosecond-assisted LASIK for low to moderate myopic astigmatism

Aim To compare astigmatic correction between femtosecond-assisted laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). Methods A total of 111 patients were included in this prospective study. Fifty-seven eyes were treated with LASIK and 54 eyes were treated with SMILE for myopia with low to moderate (−0.25 to −4.0 D) astigmatism. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity and manifest refraction were measured preoperatively and at 1 and 3 months postoperatively. Visual and refractive outcomes were reported. Changes in refractive astigmatism were evaluated using vector analysis. Results Preoperative characteristics were similar between both groups. The UDVA at 1 and 3 months was better in the LASIK group compared with the SMILE group (p<0.009). Postoperative cylinder was higher in the SMILE group (p<0.001). Fewer eyes attained the attempted cylindrical correction in the SMILE group (p<0.029). Vector analysis showed no significant difference in target-induced astigmatism (p=0.091) and angle of error (p>0.596) between the two groups. Surgically induced astigmatism was significantly lower in the SMILE group (p<0.023), while the difference vector (p<0.001) and absolute angle of error (p<0.016) were significantly higher in the SMILE group. No significant difference was found in these parameters between 1 and 3 months in both groups (p>0.122). Conclusions Our results showed that SMILE offered a less favourable astigmatic correction comparable to femtosecond-assisted LASIK in eyes with low to moderate myopic astigmatism. The alignment of treatment was more variable in SMILE, leading to a lower efficacy compared with LASIK by 3 months postoperatively.

Predisposing Factors, Microbial Characteristics, and Clinical Outcome of Microbial Keratitis in a Tertiary Centre in Hong Kong: A 10-Year Experience

Purpose. To study the risk factors, microbial profile, antibiotic susceptibility pattern, and outcome for microbial keratitis over the past 10 years in a tertiary center in Hong Kong. Methods. All cases with corneal scraping performed in Queen Mary Hospital, Hong Kong from January 2004 to December 2013 were included. Clinical outcome was defined as poor if the final visual acuity (VA) was abnormal or worse than presenting VA, a major complication occurred, or therapeutic keratoplasty was required. Results. 347 scrapes were performed in the 10-year period growing 130 microorganisms (32.3% culture positive rate). Contact lens use was the commonest risk factor. The commonest isolates were coagulase-negative Staphylococcus and Pseudomonas aeruginosa. Fluoroquinolone susceptibility was tested in 47 Gram-negative bacteria with 93.6% susceptibility (100% for Pseudomonas). 90.7% of cases had good visual outcome. Multivariate logistic regression showed age (p = 0.03), trauma (p = 0.006), and ulcer size >3 mm (p = 0.039) to be independently associated with poor outcome. Conclusion. There was no shifting trend in the isolate distribution or emergence of resistant strains in our study. Contact lens wear was the commonest risk factor, with Pseudomonas being the most frequent isolate in this group. It remained 100% susceptible to fluoroquinolones and 97% cases had good visual outcome.

Comparison of the Central and Peripheral Corneal Stromal Demarcation Line Depth in Conventional Versus Accelerated Collagen Cross-Linking.

Purpose: To compare the stromal demarcation line depth at the corneal center and its periphery in conventional versus accelerated collagen cross-linking (CXL). Methods: Patients with keratoconus who received either conventional 30-minute CXL with 3.0 mW/cm2 irradiation intensity (group 1) or accelerated 10-minute CXL with 9.0 mW/cm2 irradiation intensity (group 2) were included. The stromal demarcation line at the corneal center and 3-mm periphery measured at the first postoperative month using anterior segment optical coherence tomography were compared. Results: Thirty-three patients were included (18 in group 1, 15 in group 2) in this study. The mean demarcation line depth at center was 295 ± 62 &mgr;m in group 1 and 203 ± 45 &mgr;m in group 2 (P < 0.001). The mean depths at 3-mm periphery (nasal, temporal, superior, and inferior) in group 1 were 260 ± 64 &mgr;m, 269 ± 44 &mgr;m, 232 ± 46 &mgr;m, and 242 ± 66 &mgr;m, respectively. The corresponding measurements in group 2 were 204 ± 62 &mgr;m, 201 ± 55 &mgr;m, 196 ± 68 &mgr;m, and 189 ± 53 &mgr;m. Apart from the superior peripheral cornea (P = 0.064), the demarcation line depth measured at other peripheral regions was deeper in group 1 compared to that of group 2 (P < 0.015). The peripheral demarcation line depth was significantly shallower than observed in the central line depth for group 1 (P = 0.001), but not for group 2 (P = 0.177). Conclusions: The stromal demarcation line depth was shallower after accelerated CXL compared to that of conventional CXL at the corneal center and its periphery. The volume of cross-linked stroma appears to be larger after conventional CXL compared to its accelerated counterparts.

Use of Atropine for Prevention of Childhood Myopia Progression in Clinical Practice.

Objective: The most effective strategy to reduce myopia-related complications is to prevent myopia progression during childhood. This review article examines the latest published evidence on the use of atropine in childhood myopia control and discusses practical aspects of applying the findings to clinical practice. Future directions including possible forms of combination therapy are examined. Methods: A literature search with a focus on randomized controlled trials (RCTs) and meta-analyses on the subject was conducted. Observational studies with control groups were also reviewed to discuss issues regarding feasibility of using atropine for myopia control in clinical practice. Results: Five RCTs and 2 meta-analyses were found. The studies all found beneficial effects of atropine in myopia control, as well as a clear but perhaps clinically insignificant dose-response relationship between atropine and myopia progression rates. Available evidence however is focused on predominantly Chinese populations, and there is a current lack of guidance on timing of therapy initiation, duration of therapy, and treatment cessation. For future directions, combining atropine with other forms of myopia control would be worth considering. Conclusions: Atropine is robust option for childhood myopia control. Further evidence including RCTs in different populations as well as the upcoming 5-year atropine for the treatment of myopia 2 trial results will provide much needed answers for wider acceptance of its use.

Prevalence of ocular abnormalities in adults with Down syndrome in Hong Kong

Background/aims This was a cross-sectional survey to find the prevalence of visual impairment and eye diseases among adults with Down syndrome (DS) in Hong Kong. Methods 91 DS patients over the age of 30 were recruited through the Hong Kong Down Syndrome Association. Each patient was provided with a complete ophthalmological assessment including best corrected visual acuity, refraction, slit lamp and fundus examination. Results In our sample, 56.6% had normal vision to mild vision impairment, 33.7% and 7.2% had moderate and severe vision impairment, respectively, and 2.4% were blind. The mean presenting distant LogMAR visual acuity was 0.66 (Snellen equivalent 20/90), and the best corrected LogMAR visual acuity was 0.48 (Snellen equivalent 20/60). Significant refractive errors were found in 86.3% of the eyes, with spherical equivalent corrections ranging from −23.25D to +3.00D. Myopia and astigmatism were prevalent and found in 59.3% and 72.7% of the eyes, respectively. Blepharitis and chalazion were found in 44% of the eyes, while corneal problems were present in 27.5%. There were low incidences of infective keratitis (0.5%), keratoconus (0.5%) and Brushfield spots (1.1%). Cataracts were found in 72.2% of the eyes; 26.1% were congenital and 44.9% were age-related. Fundal abnormalities were present in 49.5% of the eyes. Conclusions There is a high prevalence of vision impairment among Chinese DS adults. Uncorrected refractive errors, high myopia and cataracts are the main visually debilitating ophthalmological abnormalities. Vision may be improved through the simple use of glasses and early treatment of age-related cataracts.

Use of anti-vascular endothelial growth factor in the management of pterygium

The rising success of anti‐vascular endothelial growth factor (VEGF) therapies in ocular disease has stimulated the use of such treatments in the surgical management of pterygium. We reviewed the literature to better understand the safety and efficacy of the adjunctive role of anti‐VEGF treatments for pterygium excision. Without surgery, anti‐VEGF alone may favourably alter symptoms and vascularity, but does not cause pterygium regression. Some evidence supports the use of anti‐VEGF as an adjuvant therapy to surgery, especially when using a higher dose and a more frequent dosing regimen. Overall, anti‐VEGF is generally safe and well tolerated in patients with pterygium. Currently, the evidence does not conclusively support the use of anti‐VEGF in pterygium surgery. However, further research may guide unanswered questions regarding the interaction between VEGF and other factors responsible for pterygium growth. In addition, the optimal route and dosage of anti‐VEGF administration is not yet known.

Early outcomes after small incision lenticule extraction and photorefractive keratectomy for correction of high myopia.

We prospectively compared visual and refractive outcomes in patients with high myopia and myopic astigmatism after small-incision lenticule extraction (SMILE) and photorefractive keratetctomy (PRK) with mitomycin C. Sixty-six eyes of 33 patients (mean age, 29.7 ± 5.6 years) were included (SMILE: 34 eyes, PRK 32 eyes). Preoperatively, no significant difference was noted in manifest spherical equivalent (p = 0.326), manifest sphere (p = 0.277), and manifest cylinder (p = 0.625) between both groups. At 1 month, there were significant differences in logMAR uncorrected distance visual acuity, efficacy index and manifest refraction spherical equivalent between SMILE and PRK (p ≤ 0.029). At 6 months, the logMAR corrected distance visual acuity (p = 0.594), logMAR uncorrected visual acuity (p = 0.452), efficacy index (p = 0.215) and safety index was (p = 0.537) was comparable between SMILE and PRK. Significant differences were observed in postoperative manifest spherical equivalent (p = 0.044) and manifest cylinder (p = 0.014) between both groups. At the end of 6 months, 100% of the eyes in SMILE group and 69% of the eyes in PRK group were within ±0.50 D of the attempted cylindrical correction. The postoperative difference vector, magnitude of error and absolute angle of error were significantly smaller after SMILE compared to PRK (p ≤ 0.040) implying a trend towards overcorrection of cylindrical correction following PRK.

Effect of the Learning Curve on Visual and Refractive Outcomes of Small-incision Lenticule Extraction

Purpose: To investigate the effect of the learning curve for small-incision lenticule extraction during the first 2 years of experience. Methods: Small-incision lenticule extraction was performed using the 500-kHz VisuMax femtosecond laser (Carl Zeiss Meditec) by the same surgeon. The initial 100 patients since the surgeon started operating independently were considered as group 1; the recent 100 patients were considered as group 2. The same laser settings and technique were used. The visual and refractive outcomes were compared between groups at postoperative 1 week and 6 months. Vector analysis was performed for eyes with astigmatic correction. Results: Two hundred right eyes of 200 patients were included. Age, preoperative corrected visual acuity, manifest refraction, and central corneal thickness were similar between groups (P ⩽ 0.154). Postoperatively, the efficacy index at 1 week was better in group 2 (group 1: 0.85 ± 0.16 vs. group 2: 0.91 ± 0.10, P = 0.019) but was similar between groups at 6 months (group 1: 0.91 ± 0.14 vs. group 2: 0.94 ± 0.08, P = 0.181). The safety index was higher in group 2 at 1 week (group 1: 0.93 ± 0.10 vs. group 2: 0.95 ± 0.08, P = 0.045) and 6 months postoperatively (group 1: 0.97 ± 0.07 vs. group 2: 0.99 ± 0.03, P = 0.011). Vector analysis showed that postoperative residual astigmatism and misalignment of astigmatic correction were lower in group 2 than in group 1 (P ⩽ 0.039) at 1 week and 6 months. The duration of docking and that of lenticule extraction was shorter in group 2 (P ⩽ 0.034). Conclusions: Our study showed that faster visual recovery, better safety profile, and more accurate astigmatic correction could be attained with increasing surgical experience.