Predictive factors for treatment outcomes with intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema in clinical practice.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the standard of care for diabetic macular edema (DME), a common complication of diabetes. This study aimed to identify factors influencing DME intravitreal anti-VEGF treatment outcomes in real-world practice. METHODS: This was a multi-center retrospective observational study using medical chart review of participants receiving anti-VEGF injections for DME (N = 248). Demographic and clinical variables were assessed for association with best corrected visual acuity (BCVA) and central macular thickness (CMT) outcomes using regression models. RESULTS: There was a significant improvement in BCVA (p < 0.001) and CMT (p < 0.001) after 12 months of treatment, although 21% of participants had decreased BCVA, and 41% had a < 10% CMT reduction at 12 months. Higher baseline BCVA (p = 0.022, OR=-0.024, 95% CI=-0.046,-0.004) and longer duration of diabetic retinopathy (p = 0.048, OR=-0.064, 95% CI=-0.129,-0.001) were negative predictors for BCVA response, whereas Aflibercept treatment (p = 0.017, OR = 1.107, 95% CI = 0.220,2.051) compared with other drugs and a positive "early functional response" (p < 0.001, OR=-1.393, 95% CI=-1.946,-0.857) were positive predictors. A higher baseline CMT (p < 0.001, OR = 0.019, 95% CI = 0.012,0.0261) and an "early anatomical response", (p < 0.001, OR=-1.677, 95% CI=-2.456, -0.943) were predictors for greater reduction in CMT. Overall, the variables could predict only 23% of BCVA and 52% of CMT response. CONCLUSIONS: The study shows a significant proportion of DME patients do not respond to anti-VEGF therapy and identifies several clinical predictors for treatment outcomes. TRIAL REGISTRATION: The study was approved through the Human Research Ethics Committee, University of Tasmania (approval number H0012902), and the Southern Adelaide Clinical Human Research Ethics Committee (approval number 86 - 067).

Identifying Genetic Biomarkers Predicting Response to Anti-Vascular Endothelial Growth Factor Injections in Diabetic Macular Edema.

Intraocular anti-vascular endothelial growth factor (VEGF) therapies are the front-line treatment for diabetic macular edema (DME); however, treatment response varies widely. This study aimed to identify genetic determinants associated with anti-VEGF treatment response in DME. We performed a genome-wide association study on 220 Australian patients with DME treated with anti-VEGF therapy, genotyped on the Illumina Global Screening Array, and imputed to the Haplotype Reference Consortium panel. The primary outcome measures were changes in central macular thickness (CMT in microns) and best-corrected visual acuity (BCVA in ETDRS letters) after 12 months. Association between single nucleotide polymorphism (SNP) genotypes and DME outcomes were evaluated by linear regression, adjusting for the first three principal components, age, baseline CMT/BCVA, duration of diabetic retinopathy, and HbA1c. Two loci reached genome-wide significance (p < 5 × 10−8) for association with increased CMT: a single SNP on chromosome 6 near CASC15 (rs78466540, p = 1.16 × 10−9) and a locus on chromosome 12 near RP11-116D17.1 (top SNP rs11614480, p = 2.69 × 10−8). Four loci were significantly associated with reduction in BCVA: two loci on chromosome 11, downstream of NTM (top SNP rs148980760, p = 5.30 × 10−9) and intronic in RP11-744N12.3 (top SNP rs57801753, p = 1.71 × 10−8); one near PGAM1P1 on chromosome 5 (rs187876551, p = 1.52 × 10−8); and one near TBC1D32 on chromosome 6 (rs118074968, p = 4.94 × 10−8). In silico investigations of each locus identified multiple expression quantitative trait loci and potentially relevant candidate genes warranting further analysis. Thus, we identified multiple genetic loci predicting treatment outcomes for anti-VEGF therapies in DME. This work may potentially lead to managing DME using personalized treatment approaches.

The effect of insulin on response to intravitreal anti-VEGF injection in diabetic macular edema in type 2 diabetes mellitus.

OBJECTIVES: To assess whether insulin therapy impacts the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of diabetic macular edema (DME) in type 2 diabetes mellitus. METHODS: This was a retrospective multi-center analysis. The best-corrected visual acuity (BCVA) at 12 months, BCVA change, central macular thickness (CMT), CMT change, and cumulative injection number were compared between the insulin and the oral hypoglycemic agent (OHA) groups. RESULTS: The mean final BCVA and CMT improved in both the insulin (N = 137; p < 0.001; p < 0.001, respectively) and the OHA group (N = 61; p = 0.199; p < 0.001, respectively). The two treatment groups were comparable for final BCVA (p = 0.263), BCVA change (p = 0.184), final CMT (p = 0.741), CMT change (p = 0.458), and the cumulative injections received (p = 0.594). The results were comparable between the two groups when stratified by baseline vision (p > 0.05) and baseline HbA1c (p > 0.05). CONCLUSION: Insulin therapy does not alter treatment outcomes for anti-VEGF therapy in DME.

Minimally invasive glaucoma surgery: Comparison of iStent with iStent inject in primary open angle glaucoma.

IMPORTANCE: Minimally invasive glaucoma surgery has gained significant traction in recent years. This study evaluates the first- and second-generation trabecular micro-bypass stents "iStent" and "iStent inject". BACKGROUND: To evaluate and compare the effect of a single iStent and double iStent inject in primary open angle glaucoma. DESIGN: Prospective comparative case series. PARTICIPANTS: Primary open angle glaucoma patients undergoing trabecular micro-bypass stent insertion combined with cataract surgery. METHODS: Baseline demographic information, preoperative, intraoperative and postoperative outcomes including intraocular pressure (IOP), visual acuity, reliance on glaucoma medication and complications were collected and analysed. MAIN OUTCOME MEASURES: Primary, secondary and tertiary outcome measures were consecutively defined as an IOP of ≤18 mmHg with zero medications, an IOP of ≤18 mmHg with reduced medications or a 20% reduction in IOP with or without medication. RESULTS: The study comprised 145 eyes in the iStent and 100 eyes in the iStent inject group. At 12 months, 56.0% of the iStent and 51.3% of the iStent inject eyes had achieved primary success and 63.1% and 57.7% secondary success. The mean postoperative IOP was 16.6 mmHg in iStent and 16.9 mmHg in iStent inject. Survival analysis demonstrated a greater incidence of failure in the iStent inject beyond 5 months. CONCLUSIONS AND RELEVANCE: Both trabecular micro-bypass stents in this study were effective in reducing IOP and the burden of medication when combined with cataract surgery. There was no statistically significant difference between the two groups across our outcome measures although the iStent inject required earlier recommencement of medications for optimal IOP control.

Small aperture IC-8 intraocular lens in cataract patients: achieving extended depth of focus through small aperture optics.

BACKGROUND: To investigate visual outcomes following cataract surgery in patients who were implanted monocularly with an extended range of focus IC-8 IOL. METHODS: A multicentre, non-randomised, retrospective case series of 126 consecutive patients implanted with the IC-8 IOL. Data were collected and pooled from six centres across Australia. Uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) at 80 cm and uncorrected near visual acuity (UNVA) at 40 cm were measured in eyes implanted with the IC-8 IOL. Adverse events, spectacle independence, visual symptoms and patient satisfaction were assessed at final follow-up. RESULTS: Over 90% of the patients without pre-existing ocular pathology (n = 109) achieved UDVA, UIVA and UNVA of 6/12 or better in the IC-8 eye. Binocularly, in this group, 98% achieved UDVA of 6/9, 94% UIVA of 6/12 and 91% UNVA of 6/12 or better. By final follow-up, over 50% of patients reported complete spectacle independence for distance, intermediate and near visual activity, with the remainder only using spectacles for specific tasks such as near-vision hobbies and reading in dim light. CONCLUSIONS: The IC-8 IOL is capable of providing extended depth of focus following cataract surgery. It allows complete spectacle independence in more than half of the patients implanted with the IC-8 IOL.

Intraoperative performance and ultrastructural integrity of human capsulotomies created by the improved precision pulse capsulotomy device.

PURPOSE: To investigate the intraoperative performance and the ultrastructural features of anterior capsulotomy performed with the improved Zepto precision pulse capsulotomy (PPC) device. SETTING: Launceston Eye Institute, Launceston, Tasmania, Australia. DESIGN: Prospective, consecutive case series. METHODS: Intraoperative observation of performance and complications were made on consecutive eyes having capsulotomies with the improved PPC device. The capsulotomy specimens were examined under scanning electron microscope and compared with manual continuous curvilinear capsulorhexis and femtosecond laser-assisted cataract surgery specimens. RESULTS: The study comprised 52 eyes. Intended capsulotomy occurred in 50 eyes with 2 device failures. Complete free-floating capsulotomies were achieved in 48 eyes (96%). Anterior capsule tears occurred in 2 eyes (4%). CONCLUSIONS: The ability of the PPC device to create complete free-floating capsulotomies improved; however, the radial tear rate remained high. The ultrastructural features in ex vivo human capsulotomy specimens still showed areas of irregular capsule margin with frayed edges.

Thermal capsulotomy: Initial clinical experience, intraoperative performance, safety, and early postoperative outcomes of precision pulse capsulotomy technology.

PURPOSE: To assess the clinical safety and performance of a new thermal capsulotomy device in patients having cataract surgery. SETTING: Launceston Eye Institute, Launceston, Tasmania, Australia. DESIGN: Prospective case series. METHODS: This single-surgeon consecutive series comprised eyes having capsulotomy with a precision pulse capsulotomy (PPC) device (Zepto). Baseline demographic information and preoperative, intraoperative, and early postoperative outcomes, including complications, intraocular pressure (IOP), flare photometry, corneal and retinal thickness, and specular microscopy were collected and analyzed. Outcomes included PPC performance, intraoperative complications, effective phacoemulsification time, IOP, postoperative inflammation, corneal edema, endothelial cell density, functional evaluation of the corneal endothelium, retinal thickness, cost-effectiveness, and early postoperative visual acuity. RESULTS: The study evaluated 100 eyes. Complete free-floating capsulotomy was achieved in 70 eyes (72%). Focal attachments were identified in 17 eyes (18%) and broad attachments in 10 eyes (10%). Intended PPC capsulotomy failed in 3 eyes due to operator or device error. Anterior capsule tears occurred in 4 eyes (4%); otherwise, there were no significant safety signals in the early postoperative period. There was no evidence of a learning curve effect; however, use of a dispersive ophthalmic viscosurgical device (OVD) is postulated as influencing capsulotomy completeness. CONCLUSIONS: The PPC device created round, reproducible, appropriately sized capsulotomies in 72% of eyes. The incidence of incomplete capsulotomy and radial tear rate was high and was possibly associated with the use of a dispersive OVD.

An analysis of ranibizumab treatment and visual outcomes in real-world settings: the UNCOVER study.

PURPOSE: To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia-Pacific region. METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed. RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 µm. The greatest mean CRT change was observed in the self-paid group, with -92.6 µm. CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.

PAIN AND ANTISEPSIS AFTER OCULAR ADMINISTRATION OF POVIDONE-IODINE VERSUS CHLORHEXIDINE.

PURPOSE: To investigate ocular bacterial count before and after antisepsis with aqueous chlorhexidine (AC) or povidone-iodine (PI) and to assess discomfort with each agent. METHODS: Bacterial swabs were taken from participants' eyes before and after antisepsis. These underwent microscopy, culture, and sensitivity testing. Aqueous chlorhexidine drops were administered to left eyes and PI to right eyes. Participants rated their pain (scale 0-10) for each eye but were blinded to the type of drop. RESULTS: There were 20 participants (17 women, 3 men), and the mean age was 43 years. Pain scores were significantly higher in right (PI) than in left (AC) eyes (mean 7 vs. mean 2, P < 0.001). No abnormalities were detected on specimen microscopy and gram staining. Seven preantisepsis swabs (three left and four right) grew bacteria in culture. Two postantisepsis swabs grew bacteria in primary culture plate (1 after AC and 1 after PI). For an additional one post-PI swab, bacteria were detected in enrichment broth only. CONCLUSION: The efficacy of AC and PI are similar, and patient discomfort is lower with AC. Aqueous chlorhexidine is a good alternative to PI for antisepsis before intravitreal injection.

Ultrastructural Integrity of Human Capsulotomies Created by a Thermal Device.

PURPOSE: To investigate the ultrastructural features of anterior capsulotomy performed with a thermal device, the precision pulse capsulotomy (PPC). DESIGN: Prospective, multicenter case series. PARTICIPANTS: Consecutive patients undergoing capsulotomy with the PPC device. METHODS: Prospective study of patients undergoing capsulotomy with the PPC by 2 surgeons, followed up by routine phacoemulsification cataract surgery, was undertaken. All capsulotomy specimens were collected for scanning electron microscopy (SEM). Observations were made regarding uniformity of the capsular edge and the presence of irregularities that may compromise integrity. Comparisons were made with manual continuous curvilinear capsulorrhexis. MAIN OUTCOME MEASURES: Ultrastructural features of PPC and presence of irregularities. RESULTS: Frayed appearance of the anterior capsule edge was noted in postoperative visits under slit-lamp examination. Scanning electron microscopy sampling showed a generally uniform rolled capsular edge, but interspersed with areas of irregularity with frayed appearance at the capsule margin. CONCLUSIONS: The PPC device is capable of creating reproducible, central, and precise circular capsulotomy. The ultrastructural features in ex vivo human capsulotomy specimens generally show eversion of the capsulotomy edge, but in some cases, this was accompanied by areas of irregular capsule margin with frayed edges, likely caused by dissipated thermal energy. The postoperative appearance and SEM features warrant further assessment of the PPC integrity and clinical correlation.

Femtosecond laser-assisted versus phacoemulsification for cataract extraction and intraocular lens implantation: clinical outcomes review.

PURPOSE OF REVIEW: Femtosecond laser-assisted cataract surgery (FLACS) has gained popularity in recent years with the new technology suggesting potential improvements in clinical and safety outcomes over conventional phacoemulsification cataract surgery (PCS). A decade since the advent of FLACS has given time and experience for laser technology to develop in maturity, and better quality evidence to become available. This review evaluates current evidence on the clinical and safety outcomes for FLACS in comparison to PCS. RECENT FINDINGS: FLACS technology continues to improve and with it our confidence in tackling more complex patient indications. Concurrently other new technologies such as precision pulse capsulotomy also look to deliver the biomechanically ideal 5.2 mm capsulotomy, particularly as there remain suggestions from large studies and meta-analyses of raised capsular complications with FLACS compared with PCS and IOL technology responding to advantages of a consistent capsulotomy. Visual benefits of FLACS over and above PCS also remain to be conclusively demonstrated, with equivalence but not superiority. Economic modelling continues to indicate that FLACS remains 'not' cost-effective. SUMMARY: FLACS can be considered non-inferior to conventional PCS in term of safety and clinical outcomes. However, FLACS has yet to demonstrate an overall cost-benefit to the patient.

Femtosecond laser-assisted cataract surgery, technology, outcome, future directions and modern applications.

Since its introduction in 2009 femtosecond laser-assisted cataract surgery (FLACS) has promised to revolutionize cataract surgery. Despite its promise, the assessment of FLACS's perceived benefits has proven to be far more complicated than initially might have been thought. Most studies to date have not provided validation of FLACS technology as a clinically significant advancement on our current techniques. We review FLACS technology and outcomes including detailed analysis of safety, efficacy, cost effectiveness and future prospects using data from the literature and our own published clinical experience.