Nicole Shu-Wen Chan

Use of anterior segment optical coherence tomography to predict corneal graft rejection in small animal models.

PURPOSE To correlate the degree of anterior chamber (AC) inflammation and corneal thickness evaluated by anterior segment optical coherence tomography (ASOCT) with corneal graft rejection status and to explore the value of ASOCT in assisting the diagnosis or prediction of graft rejection using a rat penetrating keratoplasty (PK) model. METHODS A total of 40 PKs were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: isograft control group (n=10), allograft untreated group (n=10), and allograft with 1% prednisolone acetate treatment group (n=20). All the grafts were evaluated for 28 days by a scoring rejection index (RI) to assess the graft opacity, edema, and neovascularization using slit lamp biomicroscopy. The AC inflammation and corneal graft thickness were assessed using ASOCT. RESULTS All the allogeneic control grafts and four of the 20 allogeneic steroid-treated grafts developed rejection episodes. In the allogeneic treated group, the rejected grafts had a significantly higher mean AC inflammation grade at 1 week (grade 3.25±0.49 vs. 1.83±0.36, P<0.001), significantly thicker central graft thickness at 2 weeks (455.25±42.42 μm vs. 381.247±12.51 μm, P=0.047), and a significantly higher RI at 4 weeks (7.75±0.63 vs. 4.60±0.13, P<0.001) compared to the nonrejected grafts. Eyes with ≥grade 3 AC inflammation at 1 week, or with ≥400 μm central graft thickness at 2 weeks, were significantly associated with graft rejection (odds ratio [OR], 15.15, P=0.009, and OR, 9.75, P=0.014, respectively). CONCLUSIONS The use of ASOCT to evaluate AC inflammation and corneal thickness aids in the early evaluation and diagnosis of graft rejection in animal models. Early increased AC inflammation was an early predictor of graft failure prior to definitive clinical evaluation.

Clinical Features of CMV-Associated Anterior Uveitis

ABSTRACT Cytomegalovirus (CMV) anterior uveitis is the most common ocular manifestation of CMV disease in immunocompetent individuals. It is thought to be due to a local reactivation of latent CMV and is usually unilateral. The acute form presents as Posner-Schlossman Syndrome, a recurrent hypertensive anterior uveitis with few granulomatous keratic precipitates. There are geographic differences in the chronic form of CMV anterior uveitis. Asian patients commonly present as Fuchs Uveitis Syndrome with diffuse stellate keratic precipitates, while the European patients present with a chronic hypertensive anterior uveitis with fewer keratic precipitates that are brown in color and located inferiorly. Characteristic features of CMV anterior uveitis include mild anterior chamber inflammation, elevated intraocular pressure, stromal iris atrophy. Synechiae, macular edema and retinitis are typically absent. CMV disease may also be associated with the development of corneal endotheliitis with a reduced endothelial cell count. Long-term complications include glaucomatous optic neuropathy and cataract formation.

Modified side-based scleral flap for intrascleral intraocular lens fixation

began during PGY4 in 9 (43%), during PGY3 in 7 (33%), and during PGY2 in 5 (24%) (Figure 2). In 1 program (5%), residents were provided preclinical and observation training but did not perform femtosecond laser–assisted cataract surgery as the primary surgeon. Twelve (57%) participating programs reported 1 to 9 cumulative femtosecond laser–assisted cataract surgery cases per resident, 3 (14%) reported 10 to 24 cases, and 5 (24%) reported 25 to 100 cases. Of these, 18 (90%) began performing cases during PGY4 and 2 (10%) during PGY3.

Capsule milking: Modification of capsulorhexis technique for intumescent cataract

We describe a single-stage modification of the continuous curvilinear capsulorhexis that facilitates creation of a well-sized round and centered capsulorhexis in an intumescent cataract. This is done without special instrumentation. The modification is based on overcoming the problem of high intralenticular pressure. It involves physically flattening the central anterior capsule, specifically over the site of puncture, simultaneous puncture and aspiration for decompression, followed by flattening of the midperiphery of the lens where the capsulorhexis can be safely initiated. This minimizes the tendency of capsulorhexis runaway and allows 1-stage creation of a well-sized capsule opening for phacoemulsification.

A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model

Purpose To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-ε-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. Methods The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results The microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions Tacrolimus-loaded microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

Demystifying viral anterior uveitis: a review

A viral aetiology should be suspected when anterior uveitis is accompanied by ocular hypertension, diffuse stellate keratic precipitates or the presence of iris atrophy. The most common viruses associated with anterior uveitis include herpes simplex virus, varicella‐zoster virus, cytomegalovirus and rubella virus. They may present as the following: Firstly, granulomatous cluster of small and medium‐sized keratic precipitates in Arlts triangle, with or without corneal scars, suggestive of herpes simplex or varicella‐zoster virus infection. Secondly, Posner‐Schlossman syndrome with few medium‐sized keratic precipitates, minimal anterior chamber cells and extremely high intraocular pressure; this is mainly associated with cytomegalovirus. Thirdly, Fuchs uveitis syndrome, with fine stellate keratic precipitates diffusely distributed over the corneal endothelium, with diffuse iris stromal atrophy but without posterior synechiae, is associated mainly with rubella or cytomegalovirus infection. In rubella, the onset is in the second to third decade. It presents with posterior subcapsular cataract, may have iris heterochromia and often develops vitritis without macular oedema. Cytomegalovirus affects predominantly Asian males in the fifth to seventh decade, the keratic precipitates may be pigmented or appear in coin‐like pattern or develop nodular endothelial lesions, but rarely vitritis. Eyes with cytomegalovirus tend to have lower endothelial cell counts than the fellow eye. As their ocular manifestations are variable and may overlap considerably, viral AU can pose a diagnostic dilemma. Thus, quantitative polymerase chain reaction or Goldmann‐Witmer coefficient assay from aqueous humour samples are preferred to confirm the aetiology and determine the disease severity as this impacts the treatment.

Suture snare technique for scleral fixation of intraocular lenses and capsular tension devices

Polytetrafluoroethylene (Gore-Tex) suture is preferred for scleral fixation of intraocular lenses or capsular tension devices as it is more resilient to breakage than polypropylene 10–0. However, manipulation of the thick calibre and overcurved configuration of the Gore-Tex needle within the eye poses a risk of damage to the intraocular structures. Existing techniques that overcome the problem of needles within the anterior chamber involve special instruments to retrieve the suture. We describe a technique that creates a suture snare from a short segment of the Gore-Tex suture borne on a 26-gauge needle, which is used to retrieve the Gore-Tex suture safely at the scleral fixation site. The suture is threaded into the bore of the needle leaving a short length extending from the hub which is secured by inserting a 1 cc syringe acting as a handle. The needle is inserted at the scleral fixation site, and the suture trailing from the needle tip forms a loop which is externalised at the main incision. This suture snare is used to retrieve the end of the Gore-Tex suture bearing the device to the scleral fixation site when the needle and the loop of the suture are withdrawn from the eye. This technique eliminates the inappropriate needle and the need for a large sclerostomy, and is cost-effective and can also be used in combination with the conjunctival-sparing Hoffman corneoscleral pocket.

Femtosecond laser-assisted cataract surgery for the white cataract

Aim To report the capsulotomy and lens fragmentation outcomes of white cataracts managed with the femtosecond laser (FL). Methods Outcomes of a prospective, observational consecutive case series of white cataracts (June 2012–November 2016) that underwent FL-assisted cataract surgery (FLACS) (Victus, Bausch+Lomb, Munich, Germany) at the Singapore National Eye Centre were audited. Data collected: patient demographics, type of white cataract, levelness of docking, anterior capsule position following laser, completeness of capsulotomy and fragmentation, best-corrected visual acuity (BCVA) at 1 month, intraoperative complications. Outcome measures: capsulotomy integrity, fragmentation capability and BCVA at 1 month. Results 58 eyes of 54 patients underwent FLACS. White cataract types included dry white (24 eyes), intumescent (28 eyes) and Morgagnian (6 eyes). Docking was level in 22 eyes (38.6%). Following FL, the anterior capsule level dropped in 20 eyes (34.5%). Incomplete capsulotomies occurred in 10 eyes (17.2%). Lens fragmentation attempted in 38 eyes was effective or partially effective in 31 eyes (81.6%). No anterior or posterior capsule tears occurred. LogMAR BCVA at 1 month was 0.073 (SD 0.09). Risk factors for incomplete capsulotomy were Morgagnian cataract and lens thickness (multiple logistic regression, p<0.01 and p=0.03, respectively). Conclusion The main complication of FLACS in white cataracts was incomplete capsulotomy (17.2%), significantly associated with Morgagnian cataracts and increased lens thickness. Lens fragmentation was effected in four-fifths of white cataracts but should be avoided in Morgagnian cataracts due to possible overlap of the lens fragmentation plan and the anterior capsule.

Tuberculin Skin Test and Interferon-γ Release Assays in the Diagnosis of Ocular Tuberculosis

The diagnosis of ocular tuberculosis (TB) is complex as it can manifest as almost any type of extra- or intraocular inflammation. It commonly presents as tuberculous uveitis, a paucibacillary disease in which investigations required for the definitive diagnosis such as mycobacterial cultures and acid-fast bacilli smears are of low sensitivity. The diagnosis of “presumed” tuberculous uveitis is often made in patients with the at-risk epidemiological background and suggestive clinical features in the presence of a positive tuberculin skin test (TST), positive interferon-γ release assay (IGRA), radiological evidence of pulmonary TB, and/or evidence of associated extrapulmonary TB infections in the absence of any other underlying disease. Due to the nonspecific nature of the mycobacterial antigens, the TST may have false-positive responses in individuals infected with nontuberculous mycobacterium or vaccinated with bacillus Calmette–Guerin. The IGRAs provide greater specificity for M. tuberculosis. However, both the TST and IGRAs cannot distinguish between latent TB infection, active TB, and previous TB and may be less useful in pediatric and elderly patients. IGRAs should not be used as a screening test or first-line investigation in tuberculous uveitis but are a useful adjunct for diagnosis. There is currently no clear consensus on the appropriate clinical approach, choice of investigation(s), or the most cost-effective testing algorithm. The choice of first-line investigation depends on endemicity of TB and cost-effectiveness.

Decision-making and management of uveitic cataract

The visual outcome of uveitic cataract surgery depends on the underlying uveitic diagnosis, the presence of vision-limiting pathology and perioperative optimization of disease control. A comprehensive preoperative ophthalmic assessment for the presence of concomitant ocular pathology, with particular emphasis on macula and optic nerve involvement, is essential to determine which patients will benefit from improved vision after cataract surgery. Meticulous examination in conjunction with adjunct investigations can help in preoperative surgical planning and in determining the need for combined or staged procedures. The eye should be quiescent for a minimum of 3 months before cataract surgery. Perioperative corticosteroid prophylaxis is important to reduce the risk of cystoid macular edema and recurrence of the uveitis. Antimicrobial prophylaxis may also reduce the risk of reactivation in eyes with infectious uveitis. Uveitic cataracts may be surgically demanding due to the presence of synechiae, membranes, and pupil abnormalities that limit access to the cataract. This can be overcome by manual stretching, multiple sphincterotomies or mechanical dilation with pupil dilation devices. In patients <2 years of age and in eyes where the inflammation is poorly controlled, intraocular lens implantation should be deferred. Intensive local and/or oral steroid prophylaxis should be given postoperatively if indicated. Patients must be monitored closely for disease recurrence, excessive inflammation, raised intraocular pressure, hypotony, and other complications. Complications must be treated aggressively to improve visual rehabilitation. With proper patient selection, improved surgical techniques and optimization of peri- and post-operative care, patients with uveitic cataracts can achieve good visual outcomes.