Hla Myint Htoon

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.

Diagnosis of Tuberculous Uveitis: Clinical Application of an Interferon-gamma Release Assay

PURPOSE To determine the role of the QuantiFERON-TB Gold In-Tube (QFT) (Cellestis Inc., Carnegie, Australia) assay in the diagnosis of tuberculosis (TB) uveitis. DESIGN Retrospective cohort study. PARTICIPANTS The study included 157 patients with suspected TB uveitis seen over an 18-month period (August 1, 2006, to February 31, 2007) at the Singapore National Eye Center (SNEC) uveitis clinic. METHODS We identified all cases of suspected TB uveitis in the above-mentioned time period and reviewed all medical records of the cases. Clinical findings, type of treatment instituted, response to treatment, and results of investigations such as QFT, tuberculin skin test (TST), and chest x-rays were recorded. A novel method of using treatment response to determine the presumed diagnosis of TB was used to estimate the accuracy of QFT and TST. MAIN OUTCOME MEASURES The positive likelihood ratio (LR+), negative likelihood ratio (LR-), and area under the receiver operator characteristic curve (ROC) of the investigations were estimated. RESULTS QFT is not superior to the TST in sensitivity as a screening test or first-line study in TB-related uveitis; however, QFT is more specific than the TST in identifying infections by Mycobacterium tuberculosis. Negative QFT tests should be interpreted with caution, because they do not exclude the diagnosis. CONCLUSIONS The new QFT is only slightly superior to the TST in the diagnosis of TB uveitis. Thus, there is an important role for interpreting the QFT together with the TST. This is the first and largest study of its kind to evaluate the use of QFT in the clinical diagnosis of TB uveitis.

Outcomes of Therapeutic Deep Lamellar Keratoplasty and Penetrating Keratoplasty for Advanced Infectious Keratitis: A Comparative Study

PURPOSE To compare the therapeutic success, visual outcomes, complications, and graft survival rates of therapeutic deep anterior lamellar keratoplasty (TDALK) and therapeutic penetrating keratoplasty (TPK) for advanced infectious keratitis. DESIGN Retrospective, comparative study. PARTICIPANTS One hundred twenty-three patients (126 eyes) with medically uncontrolled infectious keratitis of bacterial, fungal, or acanthamoeba etiologies who underwent TDALK (n = 26) or TPK (n = 100 eyes; 80 nonperforated ulcers; 20 perforated ulcers; mean follow-up in TDALK, 12.9 months; in TPK, 21.3 months). METHODS We performed TDALK for infections confined to the corneal stroma and the technique used was either manual lamellar dissection or Anwars big bubble technique for total stromal removal. Therapeutic penetrating keratoplasty was performed for either nonperforated or perforated ulcers. Comparison with respect to recurrence of infection, visual acuity, graft survival, and complications was made. Baseline characteristics of the patients were analyzed using the chi-square test. Kaplan-Meier survival analysis was used to evaluate graft survival. MAIN OUTCOMES MEASURES Therapeutic success (eradication of infection) or therapeutic failure (recurrence of original infection in cornea or sclera, or as endophthalmitis), graft survival (clarity), and best-corrected visual acuity (BCVA). RESULTS Therapeutic success rate of 84.6% was achieved in the TDALK group and 88% in the TPK group (P = 0.74); of the 12 eyes with recurrence of infection in the TPK cohort, 6 developed endophthalmitis with poor outcomes. A BCVA of > or =6/9 was achieved in 50% of patients in the TDALK group and 20.2% in the TPK group (P = 0.01). Mean improvement of acuity was 7.27 lines in the TDALK group and 4.76 lines in the TPK group (P = 0.01). Kaplan-Meier survival analysis at 1 year showed better graft survival for TDALK (90%) compared with TPK (78.4%). CONCLUSIONS For medically unresponsive infectious keratitis, TDALK may be considered instead of TPK yielding similar graft survival, without an increased risk of disease recurrence.

The Singapore 5-Fluorouracil Trabeculectomy Study: Effects on Intraocular Pressure Control and Disease Progression at 3 Years

PURPOSE To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery. DESIGN Prospective, randomized, double-blinded treatment trial. PARTICIPANTS Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy. METHODS One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy. MAIN OUTCOME MEASURES Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery. RESULTS Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032). CONCLUSIONS This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Sustained Drug Release in Nanomedicine: A Long-Acting Nanocarrier-Based Formulation for Glaucoma

Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a prostaglandin derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug-nanocarrier combination were elucidated by isothermal titration calorimetry. We show, using Cryo-TEM and dynamic light scattering, that the spherical shape of the liposomes is conserved even at the highest loading of latanoprost and that specific molecular interactions between the drug and the lipid are the reasons behind improved stability and sustained release. The in vivo results clearly attest to sustained efficacy of lowering the intraocular pressure for 120 days, making this an excellent candidate to be the first truly sustained-release nanomedicine product. The mechanistic details we have uncovered should enable development of similar systems for other conditions where sustained release from nanocarriers is desired.

Visual acuity outcomes after deep anterior lamellar keratoplasty: a case-control study

Aim To compare visual outcomes between deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). Secondarily to compare refractive outcomes, complications and graft survival between the three cohorts. Methods Retrospective case-control study evaluating visual acuity outcomes (VA) following DALK with complete Descemets baring (DALKa) (modified Anwar big bubble technique—51 eyes), pre-descemetic anterior lamellar keratoplasty (DALKm) (manual technique—52 eyes) and PK (103 eyes) with mean follow-up of 13.6, 19.3 and 18.6 months, respectively. Results The common indications for surgery were corneal scars (36.4%), keratoconus (28.6%) and corneal dystrophies (13.6%). A best-corrected VA of 6/7.5 or better was achieved in 19.4% (PK), 21.6% (DALKm) and 38.5% (DALKa) of cases (p=0.02), and eyes that underwent DALKa had significantly better visual outcomes than PK (p=0.03). Complications following PK were glaucoma (15%), endothelial rejection (12%) and epithelial problems (11%); in the lamellar group, glaucoma (9%), epithelial problems (5%) and Descemets detachment (3%) were more common. The 2-year estimated probability of graft survival was 90% for PK, 98% for DALKm and 100.0% for DALKa (p=0.35). Conclusions Lamellar keratoplasty with complete baring of the Descemets membrane (DALKa) gave significantly better visual outcomes compared to PK or pre-descemetic ALK and should be the preferred from of corneal replacement in corneal disorders with healthy endothelium.

Laser in situ keratomileusis flap measurements: Comparison between observers and between spectral-domain and time-domain anterior segment optical coherence tomography.

PURPOSE: To evaluate the between‐observer (interobserver) and between‐instrument (intraobserver) variability in flap thickness measurements after laser in situ keratomileusis (LASIK) using spectral‐domain and time‐domain anterior segment optical coherence tomography (AS‐OCT). SETTING: Singapore National Eye Centre. DESIGN: Evaluation of diagnostic test or technology. METHODS: Two independent masked observers measured flap thickness 1 month after LASIK using spectral‐domain (RTVue) or time‐domain (Visante) AS‐OCT. The measurements were taken at central (0.0 mm), −1.5 mm, and +1.5 mm locations. Measurements were repeated to assess between‐instrument variability. RESULTS: There was no statistically significant difference in mean flap thickness between the 2 observers at −1.5 mm, 0.0 mm, and +1.5 mm on spectral‐domain AS‐OCT and at −1.5 mm and +1.5 mm on time‐domain AS‐OCT (P < .01). There was a statistically significant difference between the 2 observers in the central (0.0 mm) values on time‐domain AS‐OCT (P=.0008). There was stronger interobserver correlation for spectral‐domain AS‐OCT at −1.5 mm (r = 0.82), 0.0 mm (r = 0.88), and +1.5 mm (r = 0.88) than for time‐domain AS‐OCT (r = 0.73, r = 0.62, and r = 0.79, respectively). There was no statistically significant difference in between‐instrument measurements. There was stronger between‐instrument correlation with spectral‐domain AS‐OCT than with time‐domain AS‐OCT at all locations. The mean standard deviation (measure of instrument repeatability) for spectral‐domain AS‐OCT was 4.19 μm. CONCLUSION: Spectral‐domain AS‐OCT had closer agreement in between‐observer and between‐instrument measurements than time‐domain AS‐OCT and provided more consistent measurements of post‐LASIK flap thickness. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Refractive lenticule extraction: Transition and comparison of 3 surgical techniques

Purpose To describe the transition and outcomes of 3 refractive lenticule extraction (ReLEx) techniques: femtosecond lenticule extraction (FLEx), small‐incision lenticule extraction (SMILE), and pseudo small‐incision lenticule extraction. Setting Singapore National Eye Center, Singapore. Design Prospective comparative case series. Methods Refractive lenticule extraction was performed between March 1, 2010, and November 1, 2012, using the Visumax 500 kHz femtosecond laser system. The main outcome measures were the refractive efficacy, predictability, and safety over 12 months. Results The study enrolled 88 eyes. All 3 refractive lenticule extraction techniques yielded good refractive outcomes and stability over 12 months. Three months postoperatively, the mean overall efficacy index of refractive lenticule extraction was 0.89 ± 0.22 (SD), with 95.5% of eyes attaining an uncorrected distance visual acuity (UDVA) of better than 20/40 and 60.2% of better than 20/20. Of all eyes, 95.5% were within ±1.00 diopter (D) and 78.4% within ±0.50 D of the attempted correction. The mean overall safety index was 1.06 ± 0.17. At 3 months, all small‐incision lenticule extraction eyes and 96.7% of pseudo small‐incision lenticule extraction eyes had a UDVA of 20/40 or better, while femtosecond lenticule extraction eyes had a lower efficacy index (87.0%). However, efficacy was comparable in all 3 groups by 12 months (mean 0.87 ± 0.04 [standard error of the mean]; P = 1.00). Conclusion The efficacy, safety, and predictability profiles of the 3 refractive lenticule extraction techniques were good over a 12‐month follow‐up. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Postoperative risk factors influencing corneal graft survival in the Singapore Corneal Transplant Study.

PURPOSE To determine postoperative risk factors that influence long-term corneal graft survival. DESIGN Prospective cohort study. METHODS Nine-hundred one consecutive penetrating keratoplasty procedures for optical, therapeutic, or tectonic indications from the Singapore Corneal Transplant Study. Univariate and multivariate analysis was performed for postoperative risk factors; Cox proportional hazards regression with a time-dependent covariate was used for preoperative, intraoperative, donor, and postoperative risk factors in a combined model. RESULTS Raised intraocular pressure (20.7%) was the most common complication, followed by rejection (18.2%), whereas glaucoma surgery (7.9%) and repeat grafting (7.3%) were the most common procedures after penetrating keratoplasty. The primary graft failure rate was 1.4%, and late failure was seen in 9.4% of eyes. In the combined regression model, rejection (hazard ratio [HR], 3.4; P = .00), microbial keratitis (HR, 3.6; P = .00), endophthalmitis (HR, 7.7; P = .00), primary disease recurrence (HR, 73.9; P = .00), wound dehiscence (HR, 2.8; P = .02), lid surgery (HR, 2.3; P = .02), glaucoma surgery (HR, 2.46; P = .02), and repeat grafting (HR, 3.2; P = .00) were the significant postoperative failure predictors; the significant preoperative and intraoperative factors identified were female gender, graft size of less than 7 mm and more than 9 mm, primary diagnosis, preoperative inflammation, and preexisting perforation. CONCLUSIONS Postoperative complications and operative procedures after grafting have an adverse effect on graft survival.

Comparison of Visante and slit-lamp anterior segment optical coherence tomography in imaging the anterior chamber angle

AimsTo compare the diagnostic performance of two anterior segment optical coherence tomography (AS-OCT) devices in assessing the anterior chamber angle (ACA).MethodsVisante-OCT and slit-lamp-OCT (SL-OCT) were performed on 101 patients by a single operator. The AS-OCT images were processed by customised ‘dewarping’ software and assessed by two glaucoma specialists masked to clinical findings. A closed ACA was defined by the presence of contact between the iris and angle anterior to the scleral spur. Measurements of the ACA, anterior chamber depth (ACD), and pupil diameter were analysed. Gonioscopy was performed by another examiner masked to AS-OCT findings.ResultsQualitative analysis could be carried out in 83 (83%) eyes and quantitative analysis in 61 (60%) eyes. A closed angle in at least one quadrant of the eye was observed in 30 eyes with gonioscopy; Visante-OCT imaging identified 29 of 30 (97%) and SL-OCT imaging identified 27 of 30 (90%) of these eyes (P=0.50, McNemar test). Visante-OCT detected more eyes with at least one closed quadrant than SL-OCT (55 vs46 eyes, respectively, P=0.01). Overall, SL-OCT had better agreement with gonioscopy than with Visante-OCT. Both AS-OCTs showed good agreement for ACD measurements; however, SL-OCT tended to provide consistently higher ACA measurements and smaller pupil diameters than did Visante-OCT.ConclusionsBoth AS-OCT devices detected most of the eyes with closed ACA on gonioscopy. However, Visante-OCT detected more closed ACAs than did SL-OCT. The better agreement between SL-OCT and gonioscopy is likely because of the use of visible light during both examinations. The ACA measurements obtained with each device are not interchangeable.