Pairwise comparative analysis of six haplotype assembly methods based on users' experience.

BACKGROUND: A haplotype is a set of DNA variants inherited together from one parent or chromosome. Haplotype information is useful for studying genetic variation and disease association. Haplotype assembly (HA) is a process of obtaining haplotypes using DNA sequencing data. Currently, there are many HA methods with their own strengths and weaknesses. This study focused on comparing six HA methods or algorithms: HapCUT2, MixSIH, PEATH, WhatsHap, SDhaP, and MAtCHap using two NA12878 datasets named hg19 and hg38. The 6 HA algorithms were run on chromosome 10 of these two datasets, each with 3 filtering levels based on sequencing depth (DP1, DP15, and DP30). Their outputs were then compared. RESULT: Run time (CPU time) was compared to assess the efficiency of 6 HA methods. HapCUT2 was the fastest HA for 6 datasets, with run time consistently under 2 min. In addition, WhatsHap was relatively fast, and its run time was 21 min or less for all 6 datasets. The other 4 HA algorithms' run time varied across different datasets and coverage levels. To assess their accuracy, pairwise comparisons were conducted for each pair of the six packages by generating their disagreement rates for both haplotype blocks and Single Nucleotide Variants (SNVs). The authors also compared them using switch distance (error), i.e., the number of positions where two chromosomes of a certain phase must be switched to match with the known haplotype. HapCUT2, PEATH, MixSIH, and MAtCHap generated output files with similar numbers of blocks and SNVs, and they had relatively similar performance. WhatsHap generated a much larger number of SNVs in the hg19 DP1 output, which caused it to have high disagreement percentages with other methods. However, for the hg38 data, WhatsHap had similar performance as the other 4 algorithms, except SDhaP. The comparison analysis showed that SDhaP had a much larger disagreement rate when it was compared with the other algorithms in all 6 datasets. CONCLUSION: The comparative analysis is important because each algorithm is different. The findings of this study provide a deeper understanding of the performance of currently available HA algorithms and useful input for other users.

Intraobserver repeatability and interobserver reproducibility of corneal measurements in normal eyes using an optical coherence tomography-Placido disk device.

PURPOSE: To study intraobserver and interobserver reproducibility of corneal topography and aberrometry measurements using a device combining optical coherence tomography (OCT) and a Placido disk (Visante Omni). SETTING: Singapore National Eye Centre, Singapore. DESIGN: Prospective nonrandomized study. METHOD: Measurements of simulated keratometry (K), anterior mean curvature, spherical anterior and posterior elevations, 4.5 mm diameter zone aberrometry (spherical aberration, asphericity, astigmatism), pachymetry, and white-to-white (WTW) diameter were taken in normal right eyes. Mean biases and limits of agreement (LoA) were obtained using Bland-Altman analysis. RESULTS: Regarding intraobserver repeatability, the mean biases for simulated K, anterior mean curvature, spherical anterior/posterior elevation, 4.5 mm zone aberrometry, pachymetry, and WTW diameter were not statistically significant (P > .05). The LoA for the anterior mean curvature measurements were flat K, -3.96 diopters (D) and 4.86 D; steep K, -4.50 D and 4.27 D; mean K, -2.48 D and 2.09 D. The LoA for WTW were -9.90 mm and 8.74 mm. Regarding interobserver reproducibility, the mean biases for simulated K, anterior mean curvature, spherical anterior/posterior elevation, 4.5 mm zone aberrometry, pachymetry, and WTW diameter were not statistically significant (P > .05). The LoA for anterior mean curvature were flat K, -4.05 D and 4.13 D; steep K, -5.08 D and 3.85 D; mean K, -2.65 D and 2.29 D. The LoA for WTW diameter were -8.79 mm and 8.24 mm. CONCLUSIONS: The OCT-Placido device had high intraobserver and interobserver clinical reproducibility for measurements of simulated K, 4.5 mm zone aberrometry, pachymetry, and standard anterior/posterior corneal elevation. However, intraobserver and interobserver reproducibility of anterior mean curvature measurements and WTW diameter was lower. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Outcomes of the Haigis-L formula for calculating intraocular lens power in Asian eyes after refractive surgery.

PURPOSE: To report outcomes using the Haigis-L formula to calculate intraocular lens (IOL) power in Asian eyes with long axial lengths (ALs) that had previous myopic laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). SETTING: Singapore National Eye Centre, Singapore. DESIGN: Retrospective case series. METHODS: Patients with ALs greater than 25.0 mm and previous myopic LASIK or PRK who had phacoemulsification were analyzed. The emmetropic IOL power was back-calculated using the 1-month postoperative manifest refraction and compared with the emmetropic IOL power calculated with the Haigis-L formula. The primary outcome measure was the mean arithmetic prediction error, defined as the difference between the actual postoperative refractive error and the intended formula-derived refractive target. RESULTS: Sixty-two eyes (52 patients) were analyzed. The mean arithmetic prediction error was -0.44 diopter (D) ± 0.98 (SD) and the mean absolute error, 0.87 ± 0.62 D. The mean arithmetic prediction error was -0.52 ± 0.96 D in eyes with an AL less than 27.0 mm and -0.36 ± 1.00 D in eyes with an AL of 27.0 mm or greater (P = .463). The predictability of being within ±0.50 D and ±1.00 D of target was 35.7% and 63.1%, respectively, overall; 31.6% and 60.5%, respectively, in eyes with an AL less than 27.0 mm; and 39.1% and 65.2%, respectively, in eyes with an AL of 27.0 mm or greater (P = .772). CONCLUSION: The Haigis-L formula was acceptably accurate in predicting and achieving target outcomes after phacoemulsification in Asian eyes with a long AL that had previous myopic LASIK or PRK. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Comparison of outcomes of conventional WaveLight(®) Allegretto Wave(®) and Technolas(®) excimer lasers in myopic laser in situ keratomileusis.

OBJECTIVE: To compare the results of laser in situ keratomileusis for myopia using WaveLight(®) Allegretto Wave(®) Eye-Q(®) and Technolas(®) 217z excimer lasers. METHOD: A retrospective, comparative case series of 442 eyes matched for age and myopia: half each were treated with Allegretto's wavefront-optimized algorithm and Technolas PlanoScan. Outcome measures were postoperative mean logarithm of the minimum angle of resolution (logMAR) uncorrected visual acuity (UCVA), manifest refraction spherical equivalent (MRSE), cylinder, safety and efficacy indices, refractive predictability, and optical zone size selection. Refractive predictability of a subgroup treated for -2.50 to -4.0 diopter (D) was analyzed separately. RESULTS: At mean follow-up of 80.5 days, mean logMAR UCVA, mean MRSE and mean postoperative cylinder were 0.02 ± 0.07 (range -0.12 to 0.30), 0.27 ± 0.36 D (range -1.25 to 1.50 D) and -0.33 ± 0.30 D (range 0.00 to -1.50 D) for Allegretto versus 0.02 ± 0.08 (range -0.12 to 0.40), 0.095 ± 0.47 D (range -1.25 to 1.13 D) and -0.44 ± 0.5 2 D (range 0.00 to -2.25 D) for Technolas (P = 0.98, 0.80 and 0.006). Mean safety and efficacy indices were 1.05 ± 0.13 (0.75-1.33) and 0.97 ± 0.13 (0.50-1.33) for Allegretto and 1.07 ± 0.14 (0.75-1.49) and 0.97 ± 0.17 (0.40-1.49) for Technolas (P = 0.23 and 0.69). Proportions of eyes achieving postoperative MRSE within ±1.0 D, ±0.5 D, and ±0.25 D were 98.2%, 91.9% and 75.6% for Allegretto and 99.1%, 97.8% and 72.4% for Technolas (P = 0.68, 0.20 and 0.51). Mean optical zone size selected was 6.48 ± 0.10 mm (range 6.0-6.5 mm) for Allegretto and 6.38 ± 0.19 mm (range 5.6-6.6 mm) for Technolas (P < 0.001). Of the subgroup with treatment between -2.5 and -4.0 D, 86.8% and 58.5% of eyes treated with Allegretto achieved postoperative MRSE within ±0.50 D and ±0.25 D versus 70.4% and 44.4% for Technolas (P = 0.006 and 0.057). CONCLUSION: No differences were seen in postoperative mean logMAR UCVA, MRSE, safety and efficacy indices between the two lasers. Allegretto produced less residual astigmatism, possibly improved refractive predictability, and required smaller optical zone selection.

Cystoid macular edema in acute presentation of central retinal artery occlusion.

A seventy-six-year-old lady with poor vision of the left eye due to previous retinal detachment presented with acute visual loss of her right eye secondary to central retinal artery occlusion. Clinical examination showed a pale right optic disc, macular edema, and a cherry red spot. Optical coherence tomography done four hours after onset showed right acute cystoid macular edema and diffuse inner retinal thickening. Subsequent treatment with intravenous carbonic anhydrase inhibitor resulted in some visual improvement. Central retinal artery occlusion has been known to produce diffuse intraretinal edema instead of cystoids changes. We would like to discuss a case of acute cystoid macular edema in acute central retinal artery occlusion.

Survey of practice preference pattern in antibiotic prophylaxis against endophthalmitis after cataract surgery in Singapore.

To determine practice preference of prophylaxis against post-cataract surgery endophthalmitis in Singapore. Prospective nationwide survey of all registered ophthalmologists through telephone, e-mail or postal questionnaires. A response rate of 76.6% was obtained from 121 out of 158 eligible ophthalmologists. Awareness of the recommendations made by the European Society of Cataract and refractive surgeons (ESCRS) endophthalmitis study was noticed in 98 (81.0%) respondents. Out of the 121 respondents, 85 (70.2%) do not use intracameral antibiotic prophylaxis. Of the 36 respondents using intracameral antibiotics, 34 (94.4%) used cefazolin. The reasons cited for not adopting intracameral antibiotic prophylaxis included financial costs, the relatively low risk of endophthalmitis after cataract surgery, the burden of dilution and the fear of toxic anterior segment syndrome. More than half (65, 53.7%) of respondents would use intracameral antibiotic prophylaxis if it were available commercially. The most commonly practiced prophylaxis (94, 77.7%) was preoperative topical antibiotics. The majority of ophthalmologists in Singapore have not adopted the use of intracameral antibiotics, with most preferring the use of pre- and postoperative prophylactic topical antibiotics, despite knowledge of the ESCRS endophthalmitis study.

Comparison of outcomes of lamellar keratoplasty and penetrating keratoplasty in keratoconus.

PURPOSE: To compare outcomes after penetrating keratoplasty (PK) and two techniques of deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. DESIGN: Retrospective cohort study. METHODS: One hundred and twenty-five corneal transplantations comprising 100 PK and 25 DALK procedures for keratoconus at the Singapore National Eye Centre from April 1992 through December 2006 were included. DALK was performed with the modified Anwar technique (descemetic or DALKa group) in 14 eyes and manual lamellar keratoplasty (predescemetic or DALKm group) was performed in 11 eyes. RESULTS: At 12 months, the DALKa and PK groups achieved a logarithm of the minimum angle of resolution mean best spectacle-corrected visual acuity (BSCVA) of 0.15 and 0.27, respectively (P = .26), whereas the mean BSCVA of the DALKm group was 0.41 compared with the PK group (P = .12). Significance level was achieved between the DALKa and DALKm groups (P = .013). There was no significant difference in the mean spherical equivalent (P = .72) and astigmatism (P = .88) between the PK and DALK groups. The DALK group had a significantly lower incidence of complications compared with PK cases, including allograft rejection and glaucoma. Graft survival rate of both the PK and DALKa groups was 100%, whereas that of the DALKm group was 73% at 3 years after surgery (P = .000 between PK and DALKm groups). CONCLUSIONS: Visual acuity outcomes of the DALKa technique are comparable with those of PK for keratoconus, whereas DALK surgery results in fewer postoperative complications than PK. DALKa is emerging as a preferred choice among the lamellar techniques for better optical outcome. Further studies are required to provide long-term analysis of these results.