Management of corneal neovascularization: Current and emerging therapeutic approaches.

Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV.

A Review of Contact Lens-Induced Limbal Stem Cell Deficiency.

Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the corneal epithelium, leading to severe conjunctivalization of the cornea. Etiologies for LSCD span from congenital (aniridia), traumatic (chemical or thermal injuries), autoimmune (Stevens-Johnson syndrome) and iatrogenic disease to contact lens (CL) wear. Of these, CL wear is the least understood and is often a subclinical cause of LSCD. Even with recent advances in LSCD research, limitations persist in establishing the pathogenesis and treatment guidelines for CL-induced LSCD. A literature search was conducted to include original articles containing patients with CL-induced LSCD. This review will critically discuss the complex pathophysiology behind CL-induced LSCD, the underlying risk factors and epidemiology of the disease as well as methods to obtain a diagnosis. Various treatment options will be reviewed based on proposed treatment strategies.

Relationship between Postoperative Intraocular Pressure and Refractive Outcomes in Patients after Deep Anterior Lamellar Keratoplasty.

Purpose: To study the effect of intraocular pressure (IOP) on refractive outcomes after deep anterior lamellar keratoplasty (DALK). Methods: This retrospective study included eyes which underwent DALK. DALK technique involved either modified Anwar big-bubble if possible or manual anterior lamellar dissection. Our main outcome measures are postoperative IOP and refractive outcomes at postoperative week and months 1, 3, 6, and 12. Results: Fifty-nine eyes of 59 patients were included. DALK was performed for optical (93.2%) and tectonic (6.8%) purposes. 76.3% of the patients had keratoconus. Anwar's big-bubble technique was successful in 30 cases. Linear mixed-model was used to analyze the effect of the highest postoperative IOP measured prior to measurement of postoperative cylinder. Patients with greater maximum postoperative IOP measured had worse postoperative cylinder (P = 0.015) and spherical equivalent (P = 0.012). Those with IOP more than 21 mmHg had worse postoperative cylinder (P = 0.050) and spherical equivalent (P = 0.054). The method of DALK and presence of suture removal were not shown to statistically affect postoperative cylinder. Conclusion: Our study shows a positive correlation between postoperative IOP and worse spherical equivalent and cylinder post-DALK, emphasizing the need for good IOP control with IOP-lowering medication(s).

The Management of Ocular Surface Squamous Neoplasia (OSSN).

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases.

Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.

Impact of fibrin glue versus suture closure on double-headed pterygia in Asian eyes - a 7-year study in a tertiary institution.

BACKGROUND: To compare the recurrence rate and outcomes of double-headed pterygia using fibrin glue versus suture closure of conjunctival autograft. METHODS: All patients with double-headed pterygia who underwent pterygia excision with conjunctival autograft from January 2012 to January 2019 in the National University Hospital of Singapore were included. Patients were divided into 2 groups depending on whether fibrin glue or sutures were used to secure the conjunctival autograft in place. All patients had a minimum of 6 months follow-up. RESULTS: A total (26 patients) of 22 eyes had fibrin glue, while eight eyes underwent suture closure of their conjunctival autograft. Fibrin glue group had 4.5% recurrence rate, while suture group had 37.5% recurrence rate (p = .021). There is statistically significant improvement for overall visual acuity (p = .009) and cylinder (p = .002). There is also statistically significant improvement for visual acuity in the glue group (p = .026), but not in the suture group. Fibrin glue group had a shorter operation duration time compared to suture group (p < .001).There were no cases of graft dislocation, contraction or limbal stem cell deficiency. CONCLUSIONS: Low recurrence rates and good postoperative visual outcomes can be achieved with the split conjunctival autograft technique. Our study suggests that fibrin glue has an additional benefit over the use of sutures in the management of these complex cases.

Three-year outcomes of Descemet's stripping endothelial keratoplasty in eyes with pre-existing glaucoma drainage devices.

BACKGROUND: Descemet's stripping endothelial keratoplasty (DSEK) is the most common procedure for corneal transplantation. The effect of a pre-existing glaucoma drainage device on long-term surgical outcomes is uncertain. METHODS: A retrospective chart review of all DSEK cases at an academic hospital over a 10-year period was conducted. RESULTS: 37 eyes who had undergone DSEK were included for analysis. These consist of 12 eyes with pre-existing GDD (GDD group), 13 eyes with glaucoma but no previous GDD (no-GDD group), and a control group of 12 patients with no ocular comorbidities apart from the indication for DSEK (control group). Visual acuity (VA) was significantly improved amongst all 3 groups, and there was no significant difference in VA between the GDD and no-GDD groups. There were no significant differences in absolute or increase in IOP between all three groups at 3 years. Graft survival rates of the 3 groups were not significantly different at 12 months. However, at 36 months, graft survival was 63% in the GDD group compared to 81% in the no-GDD group and 92% in the control group. In the GDD group, an increase in number of preoperative glaucoma drops, and a tube location in the anterior chamber were associated with an increased hazard ratio for failure. CONCLUSIONS: Presence of a GDD adversely affects graft survival whereas glaucomatous eyes which were medically managed or surgically managed without a GDD had survival rates comparable to controls. Glaucoma-filtering surgeries may confer graft survival advantage over tube shunt surgeries after DSEK.

Disease patterns of microbial keratitis in Singapore: A retrospective case series.

PURPOSE: To investigate the disease patterns of Microbial Keratitis(MK) in patients seen in a tertiary referral hospital, to evaluate the clinical outcomes of MK and the risk factors for poorer visual outcomes. METHODS: This is a retrospective case series of all culture-positive corneal scrapings between April 2012 and October 2016. A total of 230 patients(n = 230) were included into this study. Patient demographics, clinical information and microbiological characteristics of organisms are collected. RESULTS: 64.3% of patients with MK are contact lens(CL) users. Among CL users, there is a preponderance of females(68.9%) and they tend to be younger (27.1 ± 10.6 years). The most frequently isolated organism in this study is Pseudomonas aeruginosa(51.7%) with 69.6% of cases belonging to CL users. MK in non-CL users tend to involve other organisms, such as coagulase-negative Staphylococci, Staphylococcus aureus and Streptococcus pneumoniae. Pseudomonas aeruginosa exhibits good sensitivity rates to ciprofloxacin, levofloxacin and gentamicin. Non-Pseudomonas organisms display similar sensitivities to ciprofloxacin, levofloxacin and gentamicin. MK in non-CL users is related to predisposing factors of prior ocular trauma and concomitant ocular pathology. They tend to have worse visual acuity(VA) on presentation and after treatment compared to CL users. Poorer VA outcome is associated with larger ulcers, increasing age, trauma and non-CL wearers. Successful clinical outcome is achieved in 97.8% of patients, with only 2.2% requiring further surgical intervention. CONCLUSION: CL use alters the disease patterns of MK as well as the underlying microbiological etiology. Fluoroquinolones and aminoglycosides are good empirical antibiotics for MK treatment. Early referral to a tertiary centre will likely allow for earlier treatment, which can result in better VA outcome, especially so in patients who are older, non-CL wearers and have larger ulcers with associated trauma.

Comparing Outcomes of Phacoemulsification With Femtosecond Laser-Assisted Cataract Surgery in Patients With Fuchs Endothelial Dystrophy.

PURPOSE: To compare the outcome in patients with Fuchs endothelial dystrophy (FED) who underwent standard phacoemulsification vs femtosecond laser-assisted cataract surgery (FLACS) in the treatment of visually significant cataracts. DESIGN: Retrospective, comparative, interventional case series. METHODS: Patient or Study Population: Between April 2013 and December 2016, 140 FED eyes with cataracts of all densities were included. Seventy-two eyes underwent phacoemulsification and 68 eyes underwent FLACS. Intervention or Observation Procedures: Automated noncontact specular microscopy was performed at baseline and postoperatively over a mean of 17.91 ± 10.47 months. Parameters collected include visual acuity, slit-lamp examination findings, and intraoperative findings. MAIN OUTCOME MEASURES: Pachymetry, endothelial cell density (ECD), and coefficient of variance (COV) were compared. RESULTS: Phacoemulsification had significantly greater postoperative median loss of ECD of 229.0 cells/mm2 (14.2%) compared to FLACS ECD of 133.0 cells/mm2 (6.5%) (U = 1343.0, Z = -2.241, P = .025). Mean loss of ECD was 346.524 ± 420.472 cells/mm2 and 119.964 ± 434.882 cells/mm2 for phacoemulsification and FLACS, respectively (P = .005). Mean percentage loss of ECD was 15.3% ± 17.5% for phacoemulsification and 4.4% ± 25.0% for FLACS (P = .006). Eyes that underwent phacoemulsification had 10.7% ± 15.4% mean ECD loss in the mild cataract group, and in the moderate/hard cataract group 19.5% ± 18.0%, P = .045. Eyes that underwent FLACS had 0.9% ± 22.5% mean ECD loss in the mild cataract group, and 8.2% ± 26.3% in the moderate/hard cataract group, P = .291. Comparison between procedures of mean ECD loss for moderate/hard cataracts was significant (P = .043). CONCLUSIONS: FLACS is shown to be superior to phacoemulsification in reducing postoperative endothelial cell loss in FED patients, which translates to a lower risk of corneal decompensation, especially in patients with moderate/hard cataract densities.

Optical and Tectonic Corneal Transplant Outcomes in a Tertiary Hospital in Singapore within the Singapore Corneal Transplant Registry.

INTRODUCTION: This study aimed to describe and compare corneal graft survival and optical outcomes following deep anterior lamellar keratoplasty (DALK) and Descemet's stripping automated endothelial keratoplasty (DSAEK) with penetrating keratoplasty (PK), and to document tectonic success of patch grafts. MATERIALS AND METHODS: This was a retrospective, non-randomised, comparative and descriptive cohort study. A total of 139 eyes that underwent primary keratoplasty between 2000 and 2016 were included, and the following data was extracted: demographics, clinical diagnosis and primary indication, pre- and intraoperative risk factors, postkeratoplasty outcomes, and complications. Optical success was defined as good graft clarity and best corrected visual acuity (BCVA) of 6/12 or better. Graft failure was defined as irreversible corneal oedema and loss of clarity. Tectonic success in patch grafts was defined as tectonic integrity with no repeat tectonic surgical procedure required in the postoperative period. RESULTS: The mean follow-up duration was 3.24 ± 3.47 years in the PK group (n = 16), 1.89 ± 0.86 years in the DALK group (n = 37), 2.36 ± 1.24 years in the DSAEK group (n = 53), and 2.17 ± 1.09 years in the patch graft group (n = 33). The 3-year probabilties of survival for PK, DALK, DSAEK and patch graft were 60.9%, 94.1%, 89.9%, and 67.1%, respectively. The overall percentage of complications was significantly higher for PK (81.3%), compared to DALK (48.6%), DSAEK (49.1%), and patch graft (21.2%). In the PK and DALK groups, 100% achieved DSAEK (49.1%), and patch graft (21.2%). In the PK and DALK groups, 100% achieved BCVA of 6/12 or better, while in the DSAEK group, 96.43% achieved BCVA of 6/12 or better. CONCLUSION: From a similar study cohort of Asian eyes, graft survival was superior and complications were reduced for DALK and DSAEK compared to PK, but optical outcomes were comparable. Graft survival for patch graft was expectedly lower, but the incidence of complications was low.