Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Randomized Control Trial of the Impact of Patient Decision Aid Developed for Chinese Primary Open-Angle Glaucoma Patients.

INTRODUCTION: Patient decision aid (PDA) is a tool to prompt shared decision-making. The aim of this study was to evaluate the impact of a PDA on Chinese primary open-angle glaucoma patients. METHODS: All subjects were randomized into control and PDA group. The questionnaires, including 1) glaucoma knowledge; 2) 8-item Morisky medication adherence scale (MMAS-8); 3) 10-item glaucoma medication adherence self-efficacy scale (GMASES-10); and 4) 16-item decision conflict scale (DCS), were evaluated at baseline, 3- and 6-month follow-up. RESULTS: Totally, 156 subjects participated in this study, including 77 in the control group and 79 in the PDA group. Compared to the control group, PDA group showed around 1 point more improvement in disease knowledge at both 3 and 6 months (both p < 0.05), 2.5 (95% CI: [1.0, 4.1]) and 1.9 (95% CI: [0.2, 3.7]) points more improvement in GMASES-10 at 3 and 6 months, respectively, and reduction in DCS by 8.8 (95% CI: [4.6, 12.9]) points more at 3 months and 13.5 (95% CI: [8.9, 18.0]) points more at 6 months. No difference was detected in MMAS-8. CONCLUSION: PDA led to improvement in disease knowledge and self-confidence in medication adherence and reduced decision conflict compared to control group for at least 6 months.

OCTA biomarkers in adults aged 50 and above: a prospective and cross-sectional community-based study.

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods: OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results: A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates. Conclusions: Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias. Translational Relevance: Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Efficacy of 0.01% atropine for myopia control in a randomized, placebo-controlled trial depends on baseline electroretinal response.

This study aimed to evaluate the efficacy of 18-month 0.01% atropine in 61 myopic children (aged 7-10) and the relationship with central retinal response (by multifocal electroretinogram [mfERG]) in a double-masked randomized placebo-controlled clinical trial. Global-flash mfERG was measured at baseline, while cycloplegic spherical equivalent refraction (SER) and axial length (AL) were measured at baseline and at 6-month intervals. Annualized change in SER and AL were compared between atropine and control groups, and the relationships with baseline mfERG were evaluated. Changes in SER (-0.70 ± 0.39D vs. -0.66 ± 0.41D, p = 0.63) and AL (0.32 ± 0.16 mm vs. 0.30 ± 0.22 mm, p = 0.52) were similar in atropine and control groups. Interestingly, in the placebo group, mfERG amplitude was negatively correlated with axial elongation (Rp = -0.44, p = 0.03) as in our previous study. However, in the atropine group, an opposite trend was observed that axial elongation was positively correlated with mfERG amplitude (Ra = 0.37, p = 0.04). Annualized myopia progression demonstrated similar opposite effect between atropine and placebo groups but did not reach statistical significance. An ERG screening protocol may be warranted to identify suitable candidates to reduce the likelihood of an unfavorable treatment response by 0.01% atropine.

Optic disc and peripapillary vessel density measured with optical coherence tomography angiography and its associations in Chinese adults: a large population-based study.

PURPOSE: To investigate the optic disc and peripapillary vessel density, as well as its ocular and systemic associations, in healthy eyes among adult Chinese population. METHODS: A population-based cross-sectional eye survey was conducted on Chinese adults residing in Hong Kong. 1891 eyes from 1891 participants who completed 4.5×4.5 mm optical coherence tomography angiography scans were recruited. Among the 1891 eyes, 404 were excluded due to low scan quality, optic disc or retinal disorders and non-Chinese ethnicity. The vessel densities (VDs) at nerve fibre layer plexus (NFLP) at both optic disc and peripapillary were collected for analysis. Multiple linear regression analysis was performed to determine the ocular and systemic associations of NFLP VD. RESULTS: The study included 1487 participants (men: 41.2%) with a mean age of 48.8±15.4 years. The mean NFLP VD of the whole en face image, inside disc and peripapillary region was 53.8%, 42.7% and 60.3%, respectively. In the multivariable model, decreased NFLP VDs were significantly associated with older age, male gender, longer axial length (AL) and lower Signal Strength Index. CONCLUSIONS: This large population-based cross-sectional study provided quantitative data of optic disc and peripapillary NFLP VD which may serve as a normative reference for clinical use. Apart from age, gender and AL, the scan signal strength also should be taken into consideration during the assessment of NFLP VD.

Comparison of corneal biomechanics among primary open-angle glaucoma with normal tension or hypertension and controls.

BACKGROUND: Normal tension glaucoma (NTG) is a less pressure-dependent type of glaucoma with characteristic optic neuropathy. Recently, the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree. We intended to compare dynamic corneal response parameters (DCRs) among patients with primary open-angle glaucoma with normal tension or hypertension and controls. The correlations between DCRs and known risk factors for glaucoma were also analyzed. METHODS: In this cross-sectional study, 49 NTG subjects, 45 hypertension glaucoma (HTG) subjects, and 50 control subjects were enrolled. We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG, HTG, and control groups. We also analyzed the correlations between DCRs and known risk factors for glaucoma (eg, central corneal thickness [CCT], intraocular pressure [IOP], etc). RESULTS: The maximum inverse concave radius (NTG: 0.18 [0.17, 0.20] mm-1; control: 0.17 [0.16, 0.18] mm-1; P = 0.033), deformation amplitude ratio of 2 mm (DAR 2 mm, NTG: 4.87 [4.33, 5.39]; control: 4.37 [4.07, 4.88]; P < 0.001), and DAR 1 mm (NTG: 1.62 [1.58, 1.65]; control: 1.58 [1.54, 1.61]; P < 0.001) were significantly higher in NTG than in the controls. The integrated radius (IR, NTG: 8.40 ±â€Š1.07 mm-1; HTG: 7.64 ±â€Š1.31 mm-1; P = 0.026) and DAR 2 mm (NTG: 4.87 [4.33, 5.39]; HTG: 4.44 [4.12, 5.02]; P < 0.007) were significantly higher, whereas the stiffness parameter at the first applanation (SP-A1, NTG: 91.23 [77.45, 107.45]; HTG: 102.36 [85.77, 125.12]; P = 0.007) was lower in NTG than in HTG. There were no significant differences in the DCRs between HTG and control groups (P > 0.05). In the univariate and multivariate analyses, some of the DCRs, such as IR, were negatively correlated with CCT and IOP, whereas SP-A1 was positively correlated with CCT and IOP. CONCLUSIONS: The cornea was more deformable in NTG than in HTG or controls. There were no significant differences in corneal deformability between HTG and controls. The cornea was more deformable with the thinner cornea and lower IOP.

Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-Term Clinical Outcomes.

PRECIS: Phacotrabeculectomy was more effective in reducing intraocular pressure (IOP) and glaucoma drugs than phacoemulsification alone in primary angle-closure glaucoma (PACG) eyes with cataract but was associated with more postoperative complications, up to 5 years after surgery. PURPOSE: The purpose of this study was to compare long-term clinical outcomes of phacoemulsification versus phacotrabeculectomy in PACG eyes with cataract. PATIENTS AND METHODS: The 2 initial prospective randomized controlled trials recruited PACG eyes with cataract using the same criteria and randomized these eyes to receiving either phacoemulsification or phacotrabeculectomy. Clinical data up to 5 years of follow-up were pooled for retrospective analysis. RESULTS: Clinical data of 35 patients in the phacoemulsification group and 44 patients in the phacotrabeculectomy group were analyzed. At 5 years after surgery, the mean IOP was decreased by 20.7% and 29.5% from before surgery to 5 years after phacoemulsification and phacotrabeculectomy, respectively (P<0.001 for both groups). Phacotrabeculectomy was significantly more effective than phacoemulsification in reducing IOP up to 5 years after surgery (P<0.001). At 5 years, the mean number of glaucoma drugs required±1 SD was 1.6±1.2 in the phacoemulsification group, and 0.7±1.0 in the phacotrabeculectomy group (P=0.004). Phacotrabeculectomy was associated with more postoperative complications than phacoemulsification up to 5 years (25 complications in the phacotrabeculectomy group versus 6 in the phacoemulsification group, P<0.001). CONCLUSIONS: Phacoemulsification alone reduces IOP and the need for glaucoma drugs in PACG eyes with cataracts for up to 5 years. Phacotrabeculectomy was more effective in reducing IOP and glaucoma drugs than phacoemulsification alone but was associated with more postoperative complications, up to 5 years after surgery.

Exophthalmometry values in the Hong Kong Chinese adult population from a population-based study.

This study aims to establish the range of exophthalmometry values (EV) in the adult Hong Kong (HK) Chinese population, its relationship with various anthropometric parameters, and to compare it with the EV in different ethnic groups.About 1485 adult HK Chinese were drawn from a random sample from the community-based FAMILY Cohort. Participants were interviewed, and comprehensive ophthalmological assessments were conducted. EV was measured using the Hertel's exophthalmometer.EV of both eyes from 630 male (42.4%) and 855 female (57.6%) participants, mean age 54 ±â€Š17.2 and 52 ±â€Š16 respectively were analyzed. The mean EV were found to be 15.3 ±â€Š2.8 mm in the right eye, 15.2 ±â€Š2.9 mm in the left eye for men and 14.4 ±â€Š2.7 mm in the right eye, 14.3 ±â€Š2.7 mm in the left eye for women. There were no differences in the EV between right and left eyes (P > .05). Men had significantly higher EV than women (P < .05) and age was found to be negatively correlated to EV (P < .05). Body height (r = 0.20), weight (r = 0.25), waist (r = 0.11), hip circumference (r = 0.15), body mass index (r = 0.17), interpupillary distance (r = 0.54), and axial length (AL) (r = 0.20) were all found to have statistically significant positive correlations with EV (P < .01). Spherical equivalent was found to have statistically significant negative correlation with EV (P < .01).Our study provides normative data on EV in the HK Chinese population. Height, weight, interpupillary distance, waist, hip circumference, and AL had positive correlations with EV. Spherical equivalent had negative correlation with EV. There was no significant difference in EV between the right and left eye. Age and gender had significant effect on EV.

Prospective study on a novel treatment for leaking cystic bleb: Efficacy and safety of collagen crosslinking.

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.

A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

PURPOSE: To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. METHODS: All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. RESULTS: A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s = 0.437, p = 0.003). CONCLUSION: The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

Comparison of Tear Osmolarity in Rheumatoid Arthritis Patients With and Without Secondary Sjogren Syndrome.

PURPOSE: To compare tear osmolarity (TO) and other dry eye parameters in rheumatoid arthritis (RA) patients with or without secondary Sjogren syndrome (sSS). METHODS: Consecutive patients with RA were divided into a sSS group and no-sSS group using conventional diagnostic criteria by rheumatologists using symptomatology, Schirmer test score, and anti-Ro or anti-La autoantibody status. The TO, Ocular Surface Disease Index, dry eye disease (DED) parameters [such as tear breakup time (TBUT) and corneal staining score] and the systemic inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were compared. Correlation analyses between TO and the DED parameters and inflammatory markers were also performed. RESULTS: A total of 42 cases with mean age 54.8 ± 12.3 were included, with 12 patients (29%) having sSS and 30 (71%) without sSS. TO was increased in both groups (329 ± 20 and 319 ± 25 mOsm/L, respectively), but no statistically significant difference was found between the 2 groups (P = 0.126). RA with sSS had significantly shorter TBUT, higher corneal staining score, and ESR CRP levels (P < 0.05). TO did not correlate with the Schirmer test score, but had significant positive correlations with age, corneal staining score, ESR, and CRP levels, and a significant negative correlation with TBUT. CONCLUSIONS: TO was increased in RA patients with or without sSS. There was no significant correlation between TO and the Schirmer test score, and the physician could not use TO to diagnose sSS. However, TO correlated well with both DED parameters (TBUT and corneal staining score) and systemic inflammatory markers (ESR and CRP).

Development and pilot-testing of patient decision aid for use among Chinese patients with primary open-angle glaucoma.

BACKGROUND: A patient decision aid (PDA) is a tool for shared decision making (SDM), which emphasises patient empowerment. It is useful in chronic diseases and when there are multiple, no best single treatment option. Although SDM is prevalent in Western countries, its use is limited in Chinese societies, where the adoption of a paternalistic approach is strong. Here, we report the development, acceptance and pilot test results of a PDA targeted at Chinese patients with primary open-angle glaucoma (POAG). METHODS: We developed a PDA designed for use in Chinese patients with POAG. Recruited subjects were given our PDA. Baseline evaluation included decision conflict scale (DCS), validated glaucoma adherence questionnaires and glaucoma knowledge questionnaire. Subjects were briefed through the PDA and instructed to read it that day. Three to four weeks later, follow-up questionnaire as described above were conducted with the addition of acceptance questionnaires. RESULTS: Data from 65 subjects were available. The PDA was well received among subjects. DCS improved from 48.9±20.4 at baseline to 34.3±20.3 during follow-up, with P<0.01. Validated medication adherence questionnaires and knowledge showed improvement from baseline, which was statistically significant. CONCLUSIONS: The use of PDA among Chinese subjects with POAG demonstrated positive reception and acceptance. Evaluation of its initial effects shows improvement in DCS, medication adherence and glaucoma knowledge. The implementation of SDM and PDA among Chinese subjects with POAG is encouraged. Future studies with randomised design and later evaluation time points can further reveal the impacts of PDA among Chinese subjects with POAG.

Consensual ophthalmotonic reaction in Chinese patients following augmented trabeculectomy or ExPRESS shunt implantation.

INTRODUCTION: Consensual ophthalmotonic reaction (COR) was first described in 1924. Studies following monocular application of glaucoma drops and laser trabeculoplasty showed a drop in fellow eye intraocular pressure (IOP). However, studies following monocular surgery showed heterogeneous results. The purpose of this study was to investigate the COR in Chinese patients who have received monocular filtration surgery. METHODS: A noncomparative retrospective study of 65 eyes undergoing filtration surgery in Queen Mary Hospital was conducted. The IOP was obtained at baseline and postoperative days 1, 3, 7 and 14. Patient's age, sex, type of glaucoma and surgery, preoperative medications, postoperative bleb status, and number of interventions were tabulated. The postoperative IOP measurements over both eyes were obtained, and the readings were averaged to decrease the chances of extreme readings being a one-off event and allow for regression to the mean bias. RESULTS: COR was observed in the unoperated fellow eye. The mean preoperative IOP and averaged postoperative IOP were 17.2 ±â€Š5.2 mm Hg and 20.1 ±â€Š8.9 mm Hg, respectively (P < 0.04). All medications were continued in the fellow eye or even stepped up. Twenty-three percent of patients demonstrated fellow eye IOP rise >30% from baseline, while none showed IOP drop >30% from baseline. DISCUSSION: Following monocular penetrating filtration surgery, our Chinese population demonstrated a significant fellow eye IOP increase in the early postoperative period. We should bear in mind the influence of COR and take care to measure the fellow eye IOP following monocular surgery.

Management of Primary Angle-Closure Glaucoma.

Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic enlargement of optic disc cupping and visual field loss that is secondary to ocular hypertension caused by closure of the drainage angle. Angle closure is caused by appositional approximation or adhesion between the iris and the trabecular meshwork. The main treatment strategy for PACG lies in the reduction of intraocular pressure, reopening of the closed angle, and possible prevention of further angle closure. There is no universally agreed best surgical treatment for PACG. Trabeculectomy, goniosynechialysis (GSL), glaucoma implant, and cyclodestructive procedures are effective surgical options. Each of them plays an important role in the management of PACG with its own pros and cons. Accumulating evidence is available to show the effectiveness of visually significant and visually nonsignificant cataract extraction in the treatment of PACG. Trabeculectomy and GSL are often combined with cataract extraction, which may offer additional pressure control benefits to patients with PACG. This review article will discuss laser peripheral iridotomy, argon laser peripheral iridoplasty, and surgeries such as GSL, phacoemulsification, and phaco plus glaucoma surgeries that lower intraocular pressure and also alter the anterior segment and/or drainage angle anatomy. Currently, glaucoma implants and cyclodestruction are mainly reserved for PACG patients who have failed previous filtering operations. Their role as initial surgical treatment for PACG will not be discussed.