MATERIALS AND METHODS: A review of observational studies was conducted to discuss the accuracy, tolerability and ease of use of tonometers in measuring IOP in children with glaucoma.
RESULTS: Goldmann applanation tonometry (GAT) and its portable handheld versions remain the gold standard in measuring IOP. Tono-Pen (Reichert Ophthalmic Instruments, Depew, New York, USA) and rebound tonometer (RBT) both correlate well with GAT. Although both tonometers tend to overestimate IOP, Tono-Pen overestimates more than RBT. Overestimation is more remarkable in higher IOP and corneal pathologies (such as but not limited to scarred cornea and denser corneal opacity). RBT was better tolerated than other tonometers in children and was easier to use in children of all ages.
CONCLUSIONS: RBT is the preferred tonometer for measuring IOP in children with glaucoma, as it is less traumatic, time efficient and does not require fluorescein dye or anaesthesia. However, examiners should use a second tonometer to confirm elevated IOP readings from the RBT.
AREAS COVERED: Herein, the authors discuss the various factors that contribute to the quality of studies using animal models based on the evaluation of studies published in 2022. The factors affecting the quality of studies using animal models, such as the animal species, age, and sex, are discussed, along with various methods and outcomes of studies involving different animal models of glaucoma.
EXPERT OPINION: Translating animal research data to clinical applications remains challenging. Our observations in this review clearly indicate that many studies lack scientific robustness not only in their experiment conduct but also in data analysis, interpretation, and presentation. In this context, ensuring the internal validity of animal studies is the first step in quality assurance. External validity, however, is more challenging, and steps should be taken to satisfy external validity at least to some extent.
AREAS COVERED: This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
EXPERT OPINION: Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.
METHODS: This was a prospective observational study carried out at a tertiary referral centre. POAG patients on topical antiglaucoma medications and planned for phaco-ECP were recruited. WDT was performed before surgery and 6 weeks postoperatively by drinking 10 mL/kg of water in 5 min followed by serial IOP by Goldmann applanation tonometry measurements at 15, 30, 45, and 60 min. Mean IOP, IOP fluctuation (difference between highest and lowest IOP), IOP reduction, and factors affecting IOP fluctuation were analysed.
RESULTS: Twenty eyes from 17 patients were included. Baseline IOP was similar before (14.7 ± 2.7 mm Hg) and after (14.8 ± 3.4 mm Hg, p = 0.90) surgery. There was no difference in mean IOP (17.6 ± 3.4 mm Hg vs. 19.3 ± 4.7 mm Hg pre- and postoperative, respectively, p = 0.26) or peak IOP (19.37 ± 3.74 mm Hg vs. 21.23 ± 5.29 mm Hg, p = 0.25), albeit a significant reduction in IOP-lowering medications (2.2 ± 1.15 vs. 0.35 ± 0.93, p < 0.001) postoperatively. IOP fluctuation was significantly greater (6.4 ± 3.2 mm Hg vs. 4.6 ± 2.1 mm Hg, p = 0.015) with more eyes having significant IOP fluctuation of ≥6 mm Hg (11 eyes [55%] vs. 4 eyes [20%], p < 0.001) postoperatively. Factors that were significantly associated with increased postoperative IOP fluctuations were higher preoperative IOP fluctuation (β = 0.69, 95% CI 0.379-1.582, p = 0.004) and more number of postoperative antiglaucoma medications (β = 0.627, 95% CI 0.614-3.322, p = 0.008).
CONCLUSION: Reducing aqueous production with phaco-ECP does not eliminate IOP fluctuation in POAG patients. The increase in postoperative IOP fluctuation suggests increased outflow resistance after phaco-ECP.
PATIENTS AND METHODS: A retrospective review study involving 20 eyes that underwent primary augmented trabeculectomy with mitomycin (MMC) and 10 eyes GDD implantation in 3 tertiary centres in Malaysia between 1 January 2013 and 31 December 2019. They were followed up for at least 12 months postsurgical intervention. Intraocular pressure (IOP), number of topical IOP lowering medication and complications were evaluated at 1, 3, 6 and 12 months post-intervention. Based on the IOP, the success was divided into complete and partial success, and failure. IOP and postsurgical complications were compared using the Repetitive Measure Analysis of Variance (RM ANOVA) and the Pearson chi-square test.
RESULTS: Both methods were effective in lowering the IOP. Eyes with primary augmented trabeculectomy have significant lower IOP compared to GDD implantation (p = 0.037). There was a higher incidence of postoperative hypotony (30%) in the trabeculectomy group. There was also a significant reduction of mean number of topical pressure-lowering drugs required postoperatively (p = 0.015). Complete success was achieved in 100% of eyes with trabeculectomy and 67% in GDD implantation (p = 0.047).
CONCLUSIONS: Primary augmented trabeculectomy and GDD implantation are good surgical options for the treatment of JOAG. Both methods provide IOP lowering at 1 year. However, trabeculectomy provides better pressure lowering, compared to GDD implantation in patients with JOAG.
METHOD: A meta-analysis was conducted to determine the potential impact of isometric exercise on IOP and OPP. The literature on the relationship between isometric resistance exercise and IOP was systematically searched according to the "Cochrane Handbook" in the databases of Pubmed, Web of Science, EBSCO, and Scopus through December 31, 2020. The search terms used were "exercise," "train," "isometric," "intraocular pressure," and "ocular perfusion pressure," and the mean differences of the data were analyzed using the Stata 16.0 software, with a 95% confidence interval.
RESULTS: A total of 13 studies, which included 268 adult participants consisting of 162 men and 106 women, were selected. All the exercise programs that were included were isometric resistance exercises of the lower limbs with intervention times of 1min, 2min, or 6min. The increase in IOP after intervention was as follows: I2=87.1%, P=0.001 using random-effects model combined statistics, SMD=1.03 (0.48, 1.59), and the increase in OPP was as follows: I2=94.5%, P=0.001 using random-effects model combined statistics, SMD=2.94 (1.65, 4.22), with both results showing high heterogeneity.
CONCLUSION: As isometric exercise may cause an increase in IOP and OPP, therefore, people with glaucoma and related high risk should perform isometric exercise with caution.
PURPOSE: This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults.
MATERIALS AND METHODS: Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is ≥8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors.
RESULTS: Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity.
CONCLUSION: Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma.
METHODS: A retrospective, non-comparative, analytical case series of all patients who received SL-TSCPC treatment from October 2018 to April 2019 at Hospital Tengku Ampuan Afzan, Pahang, Malaysia. Data was collected during the second week, sixth week, third month and sixth month follow-up. The primary outcome measure gave success rate at six months post-treatment. Secondary measures were changes in visual acuity, mean IOP reduction, mean number of IOP lowering medications reduced and ocular side effects noted during follow-up.
RESULTS: The success rate was 43.8% (seven eyes out of sixteen eyes) at six months post-treatment. The mean IOP reduced from 43.0mmHg±14.8mmHg pre-treatment to 24.7mmHg±12.0mmHg at two weeks post treatment with 42.6% reduction. Subsequently, mean IOP at sixth week, third month and sixth month were 33.8mmHg±16.9mmHg, 35.2mmHg±14.9mmHg, and 29.0mmHg±16.2mmHg respectively. Vision maintained in 13 patients, two patients had improvement in vision however, five patients had deterioration in vision. No serious ocular side effects were noted.
CONCLUSION: Subliminal TSCPC is a safe and alternative method of lowering IOP in moderate to advanced glaucoma over 6 months duration of follow-up. As it has good safety profile and repeatability, it is a good treatment option for patients with uncontrolled glaucoma.
METHODS: This cross-sectional study was conducted on 171 primary angle closure patients (268 eyes). Visual acuity, refraction, and ocular biometry (central anterior chamber depth [ACD], axial length [AL], and lens thickness) were recorded. Vitreous cavity length (VL) and relative lens position (RLP) were calculated.
RESULTS: A total of 92 Primary Angle Closure Suspect (PACS), 30 Primary Angle Closure (PAC), and 146 Primary Angle Closure Glaucoma (PACG) eyes were included. Chinese ethnicity formed the majority (n = 197, 73.5%), followed by Malay (n = 57, 21.3%) and Indian (n = 14, 5.2%). There was a significant female preponderance with a female to male ratio of 1.85. Mean age was 65.7 ± 7.7 years. Mean spherical equivalent was +0.33 ± 1.29 D. Approximately half (n = 137, 51%) of the eyes were hyperopic (spherical power ≥+0.5), with PACG having the highest percentage of hyperopia (n = 69, 50.4%). Myopia and emmetropia were present in 48 (17.9) and 83 (31%) eyes, respectively. Although AL and VL in myopia patients were significantly longer than emmetropic and hyperopic eyes (p < 0.001), the ACD was not significantly different (p = 0.427). While the RLP is smaller in myopic eyes, lens thickness was increased in hyperopic eyes. PACG was significantly higher in elderly patients compared to PACS and PAC (p = 0.005). A total of 37 (13.8%) eyes were blind (vision worse than 3/60) and 19 of them (51.3%) were female patients.
CONCLUSION: A decrease in RLP is predictive of angle closure disease in myopic eyes, whereas increased lens thickness contributes to angle closure disease in hyperopic eyes.
METHODS: We measured psychophysical contrast thresholds in one eye of 16 control subjects and 19 patients aged 67.8 ± 5.65 and 71.9 ± 7.15, respectively, (mean ± SD). Patients ranged in disease severity from suspects to severe glaucoma. We used the 17-region FDT-perimeter C20-threshold program and a custom 9-region test (R9) with similar visual field coverage. The R9 stimuli scaled their spatial frequencies with eccentricity and were modulated at lower temporal frequencies than C20 and thus did not display a clear spatial frequency-doubling (FD) appearance. Based on the overlapping areas of the stimuli, we transformed the C20 results to 9 measures for direct comparison with R9. We also compared mfVEP-based and psychophysical contrast thresholds in 26 younger (26.6 ± 7.3 y, mean ± SD) and 20 older normal control subjects (66.5 ± 7.3 y) control subjects using the R9 stimuli.
RESULTS: The best intraclass correlations between R9/C20 thresholds were for the central and outer regions: 0.82 ± 0.05 (mean ± SD, p ≤ 0.0001). The areas under receiver operator characteristic plots for C20 and R9 were as high as 0.99 ± 0.012 (mean ± SE). Canonical correlation analysis (CCA) showed significant correlation (r = 0.638, p = 0.029) with 1 dimension of the C20 and R9 data, suggesting that the lower and higher temporal frequency tests probed the same neural mechanism(s). Low signal quality made the contrast-threshold mfVEPs non-viable. The resulting mfVEP thresholds were limited by noise to artificially high contrasts, which unlike the psychophysical versions, were not correlated with age.
CONCLUSION: The lower temporal frequency R9 stimuli had similar diagnostic power to the FDT-C20 stimuli. CCA indicated the both stimuli drove similar neural mechanisms, possibly suggesting no advantage of FD stimuli for mfVEPs. Given that the contrast-threshold mfVEPs were non-viable, we used the present and published results to make recommendations for future mfVEP tests.
METHODS: This was a retrospective, non-interventional, cohort study using data from a Japanese medical claims database. Patients with glaucoma aged ≥20 years with a first drug claim for glaucoma treatment between 01 July 2005 and 30 October 2014 and with data for > 6 months before and after this first prescription were included. The primary endpoint was duration of drug persistence among glaucoma patients with and without the use of fixed combination drugs in the year following initiation of second-line combination treatment.
RESULTS: Of 1403 patients included in the analysis, 364 (25.94%) received fixed combination drugs and 1039 (74.06%) received unfixed combination drugs as second-line treatment. Baseline characteristics were generally comparable between the groups. A total of 39.01% of patients on fixed combination drugs, compared with 41.67% of patients on unfixed combination drugs, persisted on their glaucoma drugs 12 months post second-index date. Median persistence durations for the fixed combination drugs and unfixed combination drugs groups were 6 (95% confidence interval [CI]: 5-8) and 7 months (95% CI 6-9), respectively. Patients who received prostaglandin analogs (PGAs) were the most persistent with their treatment (n = 99, 12.84%). Patients diagnosed with primary open-angle glaucoma were less likely to experience treatment modification (hazard ratio [HR]: 0.800, 95% CI 0.649-0.986, P = 0.036), while those diagnosed with secondary glaucoma were more likely to experience treatment modification (HR: 1.678, 95% CI 1.231-2.288, P = 0.001) compared with glaucoma suspects.
CONCLUSIONS: In this retrospective claims database study, the persistence rate of second-line glaucoma combination treatment was low, with no difference in persistence between glaucoma patients receiving unfixed combination drugs compared with fixed combination drugs. Patients on PGA showed greater persistence rates compared with other treatments.
METHODS: This was a prospective observational study performed at the Glaucoma Research Centre, Montchoisi Clinic, Lausanne. In total 40 eyes with open-angle glaucoma were included. OCT-A scans were performed before glaucoma surgery, and at 1-month, 3-month, 6-month, and 12-month post-operatively. AngioVue AngioAnalytic (Optovue Inc, Fremont, CA) software was used to analyse the RNFL, FAZ, peripapillary and macular VD. Changes were analysed using analysis of variance (ANOVA) models.
RESULTS: Mean IOP dropped from 19.4 (±7.0) mmHg pre-surgery and stabilized at 13.0 (±3.1) mmHg at 12 months (p