Comparison of the Icare ic100 Rebound Tonometer and the Goldmann Applanation Tonometer in 1,000 Eyes.

BACKGROUND: Measurement of intraocular pressure (IOP) forms a crucial component in the diagnosis and management of glaucoma. Many devices have been developed to measure IOP with Goldmann applanation tonometry (GAT) considered the gold standard for IOP measurement. OBJECTIVES: The objective was to compare the IOP measured using Icare ic100 and GAT. METHODS: This cross-sectional study measured IOP in 1,000 eyes (500 left and 500 right) using the Icare ic100 and GAT. Central corneal thickness (CCT) was measured using a hand-held pachymeter. IOP measurements were investigated in all eyes, by IOP substrata, by CCT group, by number of topical glaucoma medications, and diagnosis. RESULTS: There was moderate agreement between ic100 and GAT IOP measurements (intraclass correlation coefficient 0.73). Mean IOP was significantly lower when measured by ic100 than by GAT (12.1 vs. 16.2 mm Hg, p < 0.0001). Mean ic100 IOPs were also significantly lower than mean GAT IOPs within each IOP strata ≤12 (7.9 vs. 9.7 mm Hg, p < 0.0001), 13-21 (12.1 vs. 16.6 mm Hg, p < 0.0001), and ≥22 (18.4 vs. 25.2 mm Hg, p < 0.0001) and within each subanalysis. CONCLUSIONS: The Icare tonometer consistently under estimated IOP compared to GAT, irrespective of CCT ranges and other subgroup analyses. The mean difference of 4.2 mm Hg can have significant clinical implications, particularly in the management of glaucoma patients.

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.

Uteroglobin and FLRG concentrations in aqueous humor are associated with age in primary open angle glaucoma patients.

BACKGROUND: The pathophysiological changes occurring in the trabecular meshwork in primary open angle glaucoma are poorly understood, but are thought to include increased extracellular matrix deposition, trabecular meshwork cell apoptosis, inflammation, trabecular meshwork calcification and altered protein composition of the aqueous humor. Although many proteins are present in aqueous humor, relatively few have been studied extensively, and their potential roles in primary open angle glaucoma are unknown. METHODS: Analyte concentrations in aqueous humor from 19 primary open angle glaucoma and 18 cataract patients were measured using a multiplex immunoassay. Fisher's exact test was used to assess statistical significance between groups, and correlations of analyte concentrations with age, intraocular pressure, pattern standard deviation, mean deviation, cup-to-disc ratio and disease duration since commencing treatment were tested by Spearman's method. RESULTS: CHI3L1, FLRG, HGF, MIF, P-selectin and Uteroglobin were detected in more than 50% of samples of one or both patient groups, some of which have not previously been quantified in aqueous humor. In the glaucoma but not the cataract group, significant correlations were determined with age for Uteroglobin/SCGB1A1 (rs = 0.805, p < 0.0001) and FLRG (rs = 0.706, p = 0.0007). Furthermore, HGF correlated significantly with disease duration (rs = - 0.723, p = 0.0007). There were no differences in analyte concentrations between groups, and no other significant associations with clinical descriptors that passed correction for multiple testing. CONCLUSIONS: The correlations of uteroglobin and FLRG with age in primary open angle glaucoma but not cataract may suggest a heightened requirement for anti-inflammatory (uteroglobin) or anti-calcification (FLRG) activity in the ageing glaucomatous trabecular meshwork.

TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients.

PURPOSE: Elevated intraocular pressure (IOP) is the only known modifiable risk factor for primary open angle glaucoma (POAG), and it can be caused by reduced aqueous humor outflow from the anterior chamber. Outflow is predominantly regulated by the trabecular meshwork, consisting of specialized cells within a complex extracellular matrix (ECM). An imbalance between ECM-degrading matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) within the trabecular meshwork is thought to contribute to POAG. This study aimed to quantify levels of TIMPs and MMPs in aqueous humor samples from glaucomatous and non-glaucomatous eyes, analyze MMP/TIMP ratios, and correlate results with age, IOP, and Humphrey's visual field pattern standard deviation (PSD). METHODS: Aqueous humor samples were collected from 26 non-glaucomatous control subjects before cataract surgery and 23 POAG patients undergoing trabeculectomy or cataract surgery. Analyte concentrations were measured using multiplexed immunoassays. Statistical significance was assessed with Mann-Whitney U tests, and Spearman's method was used to assess correlations with age, IOP, and PSD. RESULTS: Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0.020) were significantly increased in aqueous humor samples from POAG versus cataract samples. For the majority of MMP/TIMP molar ratios calculated for the cataract group, TIMPs outweighed MMPs. In POAG, molar ratios of MMP2/TIMP1 (p = 0.007) and MMP9/TIMP1 (p = 0.005) showed a significant decrease, corresponding to an elevated excess of TIMPs over MMPs in POAG compared to cataract samples. Conversely, MMP2/TIMP3 (p = 0.045) and MMP3/TIMP3 (p = 0.032) molar ratios increased. Several MMP/TIMP molar ratios correlated with IOP (r = 0.476-0.609, p = 0.007-0.034) and PSD (r = -0.482 to -0.655, p = 0.005-0.046) in POAG samples and with age in cataract control samples. CONCLUSIONS: An imbalance among MMPs and TIMPs was found in glaucomatous aqueous humor samples, with a shift toward raised TIMP levels. This may result in the inhibition of MMP activity, leading to an altered ECM composition in the TM and thereby contributing to increased outflow resistance.

Intraocular pressure during femtosecond laser pretreatment: comparison of glaucomatous eyes and nonglaucomatous eyes.

PURPOSE: To compare changes in intraocular pressure (IOP) during femtosecond laser pretreatment of cataract between glaucomatous eyes and nonglaucomatous eyes. SETTING: Launceston Eye Institute and Launceston Eye Hospital, Launceston, Australia. DESIGN: Nonrandomized interventional prospective case series. METHODS: Patients with clinically stable primary open-angle glaucoma (POAG) having femtosecond laser pretreatment were compared with a concurrent cohort of patients with healthy eyes having the same procedure. Pretreatment was performed using a fluid-filled optical docking system (Liquid Optics Interface). With the patient supine, the IOP was measured at 4 time points using a rebound tonometer (Icare Pro). RESULTS: The study comprised 143 eyes of 97 patients. Forty-three eyes (30.1%) had documented glaucoma. The mean baseline IOP was 20.2 mm Hg ± 4.2 (SD) in glaucomatous eyes and 18.9 ± 4.0 mm Hg in nonglaucomatous eyes (P = .06). The mean change in IOP values between each time frame and baseline was as follows: vacuum-on, 13.8 ± 9.9 mm Hg and 11.1 ± 6.9 mm Hg, respectively (P = .06); after treatment, 17.4 ± 7.4 mm Hg and 14.1 ± 7.2 mm Hg, respectively (P = .014); after undocking of vacuum, 9.9 ± 5.4 mm Hg and 8.7 ± 5.7 mm Hg, respectively (P = .24). CONCLUSIONS: Femtosecond pretreatment caused a greater transient rise in IOP after treatment and a higher residual IOP after vacuum undocking in glaucomatous eyes than in nonglaucomatous eyes. This is well tolerated short term; however, long-term implications for eyes with glaucoma are unknown at present. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Intraocular pressure during femtosecond laser pretreatment of cataract.

PURPOSE: To analyze the course of intraocular pressure (IOP) during femtosecond laser pretreatment to cataract surgery. SETTING: Launceston Eye Institute, Tasmania, Australia. DESIGN: Interventional prospective study. METHODS: Femtosecond laser pretreatment was performed using the Catalys Precision Laser System with Liquid Optics Interface. The IOP was measured using a rebound tonometer (iCare PRO) during different stages of surgery and analyzed by number of docking attempts, vacuum time, treatment time, and central corneal thickness (CCT). RESULTS: The mean baseline IOP in the 25 eyes was 17.5 mm Hg ± 2.4 (SD). During vacuum application, the mean IOP rise was 11.4 ± 3.3 mm Hg. Peak IOPs were recorded immediately after laser capsulotomy and lens fragmentation (mean 36.0 ± 4.4 mm Hg; mean increase from baseline 18.5 ± 4.7 mm Hg) and remained above baseline 2 minutes after the procedure (26.6 ± 4.0 mm Hg) (P<.001). Multiple regression analysis found no association between IOP rise and number of docking attempts, vacuum time, treatment time, or CCT. CONCLUSION: Femtosecond laser pretreatment was associated with a mean peak increase in IOP of 18.5 mm Hg from baseline and appeared to be safe and well tolerated.

Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness.

Central corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6x10(-10). The locus on chromosome 16 was associated with CCT with p = 8.95x10(-11). The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population.

Scleral wrap increases the long-term complication risk of bone-derived hydroxyapatite orbital implants.

BACKGROUND: This study was prompted by previous findings that suggested that scleral wrapping increased the rate of complications following insertion of bone-derived hydroxyapatite orbital implants and compared the long-term results of implants inserted with and without scleral wraps. METHODS: This retrospective case series reviewed the long-term outcomes of 159 patients who had undergone enucleation with insertion of a bone-derived hydroxyapatite orbital implant at Dunedin Hospital between 1977 and 2006. Implants were inserted with and without scleral wraps in 85 and 74 cases, respectively. Follow up was 0.5-27.5 years (mean 8.2 years) for the whole series and 9.7 years for the sclera group and 6.7 years for the group without sclera. Patient details were obtained from theatre records, case note review, patient interview and examination, interview of patient relatives and family general practitioner records. The main outcome measures were the rates of minor or major complications and their treatments and outcomes. RESULTS: Twenty-seven cases (17%) suffered minor complications of limited implant exposure that either healed spontaneously, with implant drilling or wound resuturing and 11 cases (7%) suffered major complications requiring explantation. Of 38 patients with postoperative complications, 31 (82%) had scleral wraps compared with 7 (18%) without sclera (P < 0.001; OR 5.14, 95% CI 2.00-14.78). CONCLUSION: Bone-derived hydroxyapatite orbital implants inserted without scleral wrap were associated with better clinical outcomes and a lower rate of long-term complications. It is therefore recommended that these implants be inserted without a scleral wrap.

Medical treatment of cataract.

The incidence of cataract continues to increase with the ageing of the population. Surgical treatment with phacoemulsification and intraocular lens implantation remains the only proven treatment. This, however, is associated with significant cost and is not readily available especially in the developing countries where the prevalence of cataract is the highest. Medical treatment of cataract is therefore a highly desired alternative. Since the last major review of medical treatment of cataract the search for an anti-cataract agent has advanced on many fronts. Some anti-cataract drugs, such as carnosine, have now reached clinical trials and showed encouraging results that warrant further investigation. The discovery of an effective medical treatment for cataract is likely to make global impact on eye health. The aims of this paper are to review the literature on the drug therapy of cataract and provide updates of the latest development.

Acute retinal necrosis post intravitreal injection of triamcinolone acetonide.

Although few data exist on the complication of intravitreal injection of triamcinolone acetonide (IVTA) in human eyes, it is generally thought to be well-tolerated. The commonest reported adverse events are raised intraocular pressure and progression of cataract. Acute retinal necrosis, as far as the authors are aware, has not been reported to be associated with IVTA in the literature before. The authors hereby report such a case in a patient who has IVTA as an adjunct to photodynamic therapy of choroidal neovascularization secondary to age-related macular degeneration.

Wegener's granulomatosis presenting with painless bulbar-conjunctival ulcer and central retinal artery occlusion.

Herein an unusual case of Wegener's granulomatosis with a painless, bulbar-conjunctival ulcer in the right eye is reported. Rapid disease progression occurred with central retinal artery occlusion in the fellow eye. Biopsy of the diseased conjunctiva confirmed the clinical diagnosis. The clinical and histopathological findings are discussed.

Absent upper eyelid skin crease: a sign of hypoglobus.

The association of an absent upper eyelid skin crease on downgaze with hypoglobus has not been described in the literature before. Herein a case of silent sinus syndrome that demonstrates this sign is described. The possible mechanism of such a sign is discussed.

Central corneal thickness is highly heritable: the twin eye studies.

PURPOSE: A classic twin study was performed to determine the heritability of central corneal thickness (CCT), an important parameter in glaucoma assessment. METHODS: The concordance of CCT between monozygotic (MZ) and dizygotic (DZ) twins was compared. A total of 256 twin pairs (131 MZ and 125 DZ) were recruited from three centers: the Twin Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Twins U.K. Adult Registry held at St. Thomas' Hospital in London. As part of an extensive ophthalmic evaluation, CCT was measured by ultrasound pachymetry. Structural equation modeling with the Mx program (Department of Psychiatry, Medical College of Virginia, Richmond, VA) was used to determine the heritability of CCT. RESULTS: The mean age of subjects was 38 years (range, 8-81). The mean CCT of all eyes examined was 544.5 +/- 37.3 mum (SD). The CCT measurements correlated more highly in MZ twins than in DZ twins, with intraclass correlation coefficients of 0.95 and 0.52, respectively, suggesting a strong genetic influence. A model of additive genetic and unique environmental effects provided the best fit, yielding a heritability of 0.95 (95% confidence interval [CI], 0.93-0.96) with the remaining variation being attributable to unique environmental factors. CONCLUSIONS: In this study of Australian and U.K. twins, genetic factors were shown to be of major importance in CCT, with a heritability of 0.95.

Post-cycloplegia myopic shift in an older population.

PURPOSE: To demonstrate that use of a mydriatic agent remains a significant confounder in autorefraction of the presbyopic population. METHODS: The pre- and post-cycloplegic autorefraction results of 37 subjects over 50 years of age were measured using a Humphrey-598 autorefractor. The results of both eyes were included in a multivariate regression analysis. RESULTS: The average age of the patient sample was 63.4 years. The mean spherical equivalent (SEQ) shifts for the hyperopic, myopic, pseudophakic, and emmetropic eyes were -0.53 D (95% CI -0.77 D to -0.39 D; p < 0.001), -0.38 D (95%CI -0.81 D to +0.04 D; p = 0.077), -0.49 D (95% CI -0.78 D to -0.20 D; p = 0.001), and -0.35 D (95% CI -0.59 D to -0.11 D; p = 0.004), respectively. CONCLUSION: Cyclopleged autorefraction in the presbyopic population is associated with a myopic shift that can potentially lead to overestimation of myopic prevalence. This is an important factor in comparing population studies where cyclogleged autorefraction is used in contrast to non-cyclopleged autorefraction and subjective refraction.