Conjunctival erosion following a PRESERFLO® MicroShunt procedure.

PURPOSE: We describe a case of conjunctival erosion following a PRESERFLO® MicroShunt procedure, and the subsequent revision surgery. OBSERVATIONS: Conjunctival erosion was noted overlying the MicroShunt implant at postoperative week 11, 8 weeks following a bleb needling procedure for bleb encapsulation. A brisk leak was observed at the site of erosion. The patient underwent a subsequent revision procedure with repositioning of the MicroShunt implant and mitomycin C (MMC) application. CONCLUSION AND IMPORTANCE: Conjunctival erosion may be a relatively rare but important complication following MicroShunt surgery and may arise from a variety of risk factors. Extra care should be taken during bleb needling in the context of MicroShunt, and needling should be directed posteriorly, beyond the distal tip of the MicroShunt.

Altered Iris Aquaporin Expression and Aqueous Humor Osmolality in Glaucoma.

Purpose: Aquaporins (AQPs) facilitate transmembrane osmotic water transport and may play a role in iris fluid conductivity, which is implicated in the pathophysiology of glaucoma. In this study, we compared the iris expression of AQPs and aqueous osmolality between primary angle closure glaucoma (PACG), primary open-angle glaucoma (POAG), and nonglaucoma eyes. Methods: AQP1-5 transcripts from a cohort of 36 PACG, 34 POAG and 26 nonglaucoma irises were measured by quantitative real-time PCR. Osmolality of aqueous humor from another cohort of 49 PACG, 50 POAG, and 50 nonglaucoma eyes were measured using an osmometer. The localization of AQP1 in both glaucoma and nonglaucoma irises was determined by immunofluorescent analysis. Results: Of the five AQP genes evaluated, AQP1 and AQP2 transcripts were significantly upregulated in both PACG (3.48- and 8.07-fold, respectively) and POAG (3.12- and 11.58-fold, respectively) irises relative to nonglaucoma counterparts. The aqueous osmolalities of PACG (303.68 mmol/kg) and POAG (300.79 mmol/kg) eyes were significantly lower compared to nonglaucoma eyes (312.6 mmol/kg). There was no significant difference in expression of AQP transcripts or aqueous osmolality between PACG and POAG eyes. Conclusions: PACG and POAG eyes featured significant increase in AQP1 and AQP2 expression in the iris and reduced aqueous osmolality compared to nonglaucoma eyes. These findings suggest that the iris may be involved in altered aqueous humor dynamics in glaucoma pathophysiology. Because PACG did not differ from POAG in both properties studied, it is likely that they are common to glaucoma disease in general.

Intraocular pressure changes following topical ocular hypotensive medications washout.

BACKGROUND: To review the changes in intraocular pressure (IOP) following topical hypotensive medications washout in patients with primary open angle glaucoma (POAG), ocular hypertension (OHT) and uveitic glaucoma (UG)/OHT. METHODS: The study included 120 patients with POAG, OHT and UG recruited from prospective clinical trials between February 2013 and July 2017. We excluded 20 eyes with IOP of ≤21 mm Hg, 11 eyes with previous incisional surgery and 17 eyes with incomplete data. UG eyes with active inflammation and on steroid treatment were excluded. Participants underwent a 1-month washout period from topical ocular hypotensive medications before IOP phasing. Comparisons were made between pre/post-washout IOP, and highest-recorded (peak) and post-washout IOP. RESULTS: A total of 110 eyes with POAG, 33 eyes with OHT and 43 eyes with UG were included for analysis. The mean pre-washout IOP was 18.1±3.3 mm Hg in POAG, 18.8±3.3 mm Hg in OHT and 17.9±8.8 mm Hg in UG; the mean post-washout IOP was 26.6±4.8 mm Hg, 26.4±3.9 mm Hg, 23.1±10.1 mm Hg in POAG, OHT and UG, respectively. The mean increase in IOP after washout was significantly lower in UG compared with POAG and OHT eyes (p=0.01). The percentage of eyes with post-washout IOP <22 mm Hg was 12.7% in POAG, 6.1% in OHT and 51.2% in UG. CONCLUSION: Active inflammation and steroid treatment contributes to elevated IOP in uveitis. Therefore, IOP may revert to normal once inflammation subsides. We recommend ocular hypotensive treatment washout to be considered in UG eyes that have IOP under control in the absence of recurrence of uveitis.

The Cost and Economics of Endoscopic Cyclophotocoagulation in the United Kingdom: A Tertiary Center Experience.

PRECIS: As the only microinvasive glaucoma surgery (MIGS) with a reusable component, the cost per procedure of endoscopic cyclophotocoagulation (ECP) diminishes with each successive use. We present a cost comparison of ECP with other MIGS devices, based on our clinical practice. PURPOSE: ECP delivers diode laser via a reusable probe to the ciliary processes under direct visualization. The aim of our study is to evaluate the direct cost of ECP based on a retrospective review of cases and compare the cost per procedure with other MIGS devices. METHODS: We conducted a retrospective review of ECP procedures performed at St Thomas' Hospital over 4.5 years. The cost of the ECP endoscope and diode laser consoles, reusable probes, and maintenance contracts were obtained from the hospital procurement log. The on-site Central Sterile Services Department was contacted for probe sterilization and repackaging costs. The cost per device for ECP and commonly performed MIGS procedures were obtained from the product specialists of each company. RESULTS: A total of 332 procedures were performed using 37 ECP probes during the study period. Each reusable ECP laser probe was found to give an average of 8.97 laser treatments. The cost per procedure decreased over the course of 4.5 years from £819.43 for the first 42 cases to £341.50 after 332 cases. Compared with other MIGS devices, the cost per procedure of ECP after 100 procedures is second lowest to the Kahook Dual Blade and reduces with each successive procedure performed. CONCLUSION: The ability to reuse each ECP probe significantly lowers the cost per procedure compared with other MIGS devices in the United Kingdom. The cost per procedure continues to reduce with each successive procedure.

Retinal Nerve Fiber Layer Thickness in a Multiethnic Normal Asian Population: The Singapore Epidemiology of Eye Diseases Study.

PURPOSE: To describe variations in retinal nerve fiber layer (RNFL) thickness based on spectral-domain (SD) OCT in a multiethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Ethnic Chinese, Malay, and Indian adults older than 48 years without glaucoma who were recruited from the Singapore Epidemiology of Eye Diseases Study. METHODS: All participants underwent standardized systemic and ocular examinations. Retinal nerve fiber layer thickness was measured using SD OCT. Participants with poor-quality scans were excluded. Linear regression models were used to investigate the associations of ocular and systemic factors with average RNFL thickness. Generalized estimating equation models were used to account for correlation between both eyes. MAIN OUTCOME MEASURE: Average RNFL thickness. RESULTS: Four thousand four hundred seventy-five participants (8178 eyes) consisting of 1371 Chinese, 1303 Malay, and 1801 Indian adults contributed to this analysis. Average RNFL thickness measured was 95.7±9.6 µm in Chinese participants, 94.9±10.6 µm in Malay participants, and 87.3±10.6 µm in Indian participants (P < 0.001). Multivariate analysis adjusted for age, gender, and ethnicity revealed a reduction in RNFL thickness with increased intraocular pressure and axial length (P < 0.001 for both), as well as a diagnosis of diabetes (P = 0.04); greater RNFL thickness was associated with increased disc area (P < 0.001), signal strength (P < 0.001), and low-density lipoprotein cholesterol (P = 0.02). When these significant variables were taken into account, the average RNFL thickness of Indian participants was significantly thinner compared with Chinese participants (7.45 µm thinner on average [95% confidence interval, 6.75-8.15 µm; P < 0.001]), whereas there was no significant difference in average RNFL thickness between Malay and Chinese participants (P = 0.15). CONCLUSIONS: Average and regional RNFL thicknesses were significantly thinner in Indian eyes compared with Chinese and Malay eyes. Results of the study highlight the need to acquire more refined normative data for the comparison of individual patients with others of similar ethnic background while accounting for ocular factors that could influence RNFL thickness. This in turn may improve the sensitivity and specificity of glaucoma detection.

Shared Cared for Stable Glaucoma Patients: Economic Benefits and Patient-centered Outcomes of a Feasibility Trial.

PURPOSE: The purpose of this article is to assess the quality of care and economic benefits of a shared care model managing patients with stable glaucoma in a primary eye care (PEC) clinic compared with a tertiary specialist outpatient clinic (SOC) in Singapore. PATIENTS AND METHODS: A randomized equivalence feasibility trial was preformed comparing the PEC with SOC models. Participants recruited from the SOC had no visual field progression or change in management for at least 3 years, were on a maximum of a single glaucoma medication, had no previous tube-shunt implant and were at least 3-year posttrabeculectomy surgery.Primary outcomes were clinical assessment and management, economic benefits, and patient satisfaction. Differences were analyzed using equivalence testing and generalized odds ratios. RESULTS: The trial included 233 patients, consisting of 42.1% glaucoma disc suspects (PEC: 47.4%; SOC: 36.8%), 27.5% primary angle closure suspects (PEC: 25.0%; SOC: 29.9%), 13.7% with ocular hypertension (PEC: 13.8%; SOC: 13.7%), 3.9% with primary angle closure glaucoma (PEC: 4.3%; SOC: 3.4%), and 3.0% with primary open angle glaucoma (PEC: 1.7%; SOC: 4.3%). Glaucoma clinical care for patients at PEC was as good as SOC [rate difference, 6.83%; 95% confidence interval (CI), 2.84-11.12) and management (rate difference, 7.69%; 95% CI, 3.21-12.17). In 23 cases (9.9%), 5.2% at PEC and 14.5% at SOC, there was disconcordance with the gold standard of senior consultant. Patient satisfaction at the PEC was equally high when compared with SOC (generalized odds ratio, 1.43; CI, 0.50-2.00). Direct costs per patient visit were 43% lower at PEC compared with SOC. CONCLUSION: Managing stable glaucoma patients at a primary care setting is a cost saving, safe, and effective shared care while enhancing professional collaboration between hospital and community settings.

Retinopathy Signs Improved Prediction and Reclassification of Cardiovascular Disease Risk in Diabetes: A prospective cohort study.

CVD risk prediction in diabetics is imperfect, as risk models are derived mainly from the general population. We investigate whether the addition of retinopathy and retinal vascular caliber improve CVD prediction beyond established risk factors in persons with diabetes. We recruited participants from the Singapore Malay Eye Study (SiMES, 2004-2006) and Singapore Prospective Study Program (SP2, 2004-2007), diagnosed with diabetes but no known history of CVD at baseline. Retinopathy and retinal vascular (arteriolar and venular) caliber measurements were added to risk prediction models derived from Cox regression model that included established CVD risk factors and serum biomarkers in SiMES, and validated this internally and externally in SP2. We found that the addition of retinal parameters improved discrimination compared to the addition of biochemical markers of estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hsCRP). This was even better when the retinal parameters and biomarkers were used in combination (C statistic 0.721 to 0.774, p = 0.013), showing improved discrimination, and overall reclassification (NRI = 17.0%, p = 0.004). External validation was consistent (C-statistics from 0.763 to 0.813, p = 0.045; NRI = 19.11%, p = 0.036). Our findings show that in persons with diabetes, retinopathy and retinal microvascular parameters add significant incremental value in reclassifying CVD risk, beyond established risk factors.

Association of Systemic Medication Use With Intraocular Pressure in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

IMPORTANCE: There is limited understanding of the associations between systemic medication use and intraocular pressure (IOP) in the general population. OBJECTIVE: To examine the association between systemic medication use and IOP in a multiethnic Asian population. DESIGN, SETTING, AND PARTICIPANTS: In this post hoc analysis of the Singapore Epidemiology of Eye Diseases study, a population-based study of 10 033 participants (78.7% response rate) from 3 racial/ethnic groups (Chinese [recruited from February 9, 2009, through December 19, 2011], Malays [recruited from August 16, 2004, though July 10, 2006], and Indians [recruited from May 21, 2007, through December 29, 2009]), participants with glaucoma, previous ocular surgery, or trauma and an IOP asymmetry greater than 5 mm Hg between eyes were excluded. Intraocular pressure was measured using Goldmann applanation tonometry. An interviewer-administered questionnaire was conducted to collect data on medication and other variables. Data analysis was performed from August 1 through October 31, 2015. MAIN OUTCOMES AND MEASURES: Associations between medication and IOP were assessed using linear regression models adjusted for age, sex, body mass index, ethnicity, and the medical condition for which the medication was taken (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], and ß-blockers adjusted for blood pressure, statins adjusted for lipids, and biguanides, sulfonylureas, α-glycosidase inhibitors [AGIs], and insulin adjusted for glycosylated hemoglobin). Medications associated with significant IOP differences were incorporated into regression models adjusted for concomitant use of multiple medications. Generalized estimating equation models were used to account for correlation between eyes. RESULTS: Of the 10 033 participants, we analyzed 8063 (mean [SD] age, 57.0 [9.6] years; 4107 female [50.9%]; 2680 Chinese [33.2%], 2757 Malay [34.2%], and 2626 Indian [32.6%] individuals). Systemic ß-blocker use was independently associated with an IOP of 0.45 mm Hg lower (95% CI, -0.65 to -0.25 mm Hg; P < .001). Conversely, higher mean IOP was associated with use of ACEIs (0.33 mm Hg higher; 95% CI, 0.08 to 0.57 mm Hg; P = .008), ARBs (0.40 mm Hg higher; 95% CI, 0.40-0.75 mm Hg; P = .02), statins (0.21 mm Hg higher; 95% CI, 0.02-0.4 mm Hg; P = .03), and sulfonylureas (0.34 mm Hg higher; 95% CI, 0.05-0.63 mm Hg; P = .02). An interaction between medication classes for additive, synergistic, or antagonistic effects on IOP was not identified. CONCLUSIONS AND RELEVANCE: Although systemic ß-blocker use was associated with lower IOP and systemic ACEI, ARB, statin, and sulfonylurea use was associated with higher IOP in this study, the associations were modest at best. Only the associations with systemic hypoglycemic agents were greater than 1 mm Hg, a threshold that has translated to a 14% greater risk of incident glaucoma across 5 years in other studies. At this point, the effect of systemic medication on IOP in eyes with glaucoma is not well elucidated but important. Our findings indicate that patients with glaucoma may potentially be at risk of higher or lower IOP, depending on medication class, and this would in turn affect management of IOP control.

Altered Anterior Segment Biometric Parameters in Mice Deficient in SPARC.

Purpose: Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related matricellular proteins involved in extracellular matrix assembly. In this study, we compared the anterior chamber biometric parameters and iris collagen properties in SPARC-, Hevin- and SPARC-/Hevin-null with wild-type (WT) mice. Methods: The right eyes of 53 WT, 35 SPARC-, 56 Hevin-, and 63 SPARC-/Hevin-null mice were imaged using the RTVue-100 Fourier-domain optical coherence tomography system. The parameters measured were anterior chamber depth (ACD), trabecular-iris space area (TISA), angle opening distance (AOD), and pupil diameter. Biometric data were analyzed using analysis of covariance and adjusted for age, sex, and pupil diameter. Expression of Col1a1, Col8a1, and Col8a2 transcripts in the irises was measured by quantitative polymerase chain reaction. Collagen fibril thickness was evaluated by transmission electron microscopy. Results: Mice that were SPARC- and SPARC-/Hevin-null had 1.28- and 1.25-fold deeper ACD, 1.45- and 1.53-fold larger TISA, as well as 1.42- and 1.51-fold wider AOD than WT, respectively. These measurements were not significantly different between SPARC- and SPARC-/Hevin-null mice. The SPARC-null iris expressed lower Col1a1, but higher Col8a1 and Col8a2 transcripts compared with WT. Collagen fibrils in the SPARC- and SPARC-/Hevin-null irises were 1.5- and 1.7-fold thinner than WT, respectively. The Hevin-null iris did not differ from WT in these collagen properties. Conclusions: SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.

Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters.

BACKGROUND: This study aimed to evaluate differences in iris gene expression profiles between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) and their interaction with biometric characteristics. DESIGN: Prospective study. PARTICIPANTS: Thirty-five subjects with PACG and thirty-three subjects with POAG who required trabeculectomy were enrolled at the Singapore National Eye Centre, Singapore. METHODS: Iris specimens, obtained by iridectomy, were analysed by real-time polymerase chain reaction for expression of type I collagen, vascular endothelial growth factor (VEGF)-A, -B and -C, as well as VEGF receptors (VEGFRs) 1 and 2. Anterior segment optical coherence tomography (ASOCT) imaging for biometric parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV) and lens vault (LV), was also performed pre-operatively. MAIN OUTCOME MEASURES: Relative mRNA levels between PACG and POAG irises, biometric measurements, discriminant analyses using genes and biometric parameters. RESULTS: COL1A1, VEGFB, VEGFC and VEGFR2 mRNA expression was higher in PACG compared to POAG irises. LV, ACD and ACV were significantly different between the two subgroups. Discriminant analyses based on gene expression, biometric parameters or a combination of both gene expression and biometrics (LV and ACV), correctly classified 94.1%, 85.3% and 94.1% of the original PACG and POAG cases, respectively. The discriminant function combining genes and biometrics demonstrated the highest accuracy in cross-validated classification of the two glaucoma subtypes. CONCLUSIONS: Distinct iris gene expression supports the pathophysiological differences that exist between PACG and POAG. Biometric parameters can combine with iris gene expression to more accurately define PACG from POAG.

Vision-related quality of life and visual outcomes after small-incision lenticule extraction and laser in situ keratomileusis.

PURPOSE: To compare vision-related quality of life (VRQoL) scores and clinical outcomes between small-incision lenticule extraction and laser in situ keratomileusis (LASIK). SETTING: Singapore National Eye Centre, Singapore. DESIGN: Prospective study. METHODS: Patients had small-incision lenticule extraction using the Visumax 500 kHz femtosecond laser; or LASIK excimer ablation with the Wavelight Allegretto 400 Hz laser. Primary outcomes were 3-month predictability, efficacy, and safety. Secondary outcomes were intraoperative experience, visual symptoms, and VRQoL (validated Quality of Life Impact of Refractive Correction [QIRC] questionnaire) in 25 a subgroup of patients in each group. Following Rasch analysis, "Functional" and "Emotional," QIRC dimensions were analysed separately. RESULTS: At 3 months, predictability (82.5% versus 85.3%, ±0.5 diopters attempted correction, P =.453), safety index (1.13 ± 0.19 [SD] versus 1.07 ± 0.16, P = .158), and efficacy index (0.91 ± 0.21 versus 0.97 ± 0.19; P = .002) were found when comparing small-incision lenticule extraction (172 eyes) and LASIK (matched 688 eyes). Intraoperative experience between groups was not statistically different; visual fluctuations (P = .020) and episodes of visual blurring (P = .008) were greater after small-incision lenticule extraction than after LASIK at 1 month but not at 3 months. There was no difference in "functional" (66.7 ± 15.7 versus 55.3 ± 22.2, P = .064) and "emotional" (42.7 ± 23.2 versus 37.9 ± 23.8, P = .394) QIRC dimensions between the 2 groups (25 patients in each group) at 3 months. CONCLUSION: The study, 3-month predictability, safety, and VRQL scores were not statistically different between small-incision lenticule extraction and LASIK. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

A Genetic Variant in TGFBR3-CDC7 Is Associated with Visual Field Progression in Primary Open-Angle Glaucoma Patients from Singapore.

PURPOSE: To investigate whether known genetic loci for primary open-angle glaucoma (POAG) are associated with visual field (VF) progression in patients from a Singaporean Chinese population. DESIGN: Retrospective study. PARTICIPANTS: Patients with 5 or more reliable VF measurements who were being followed up at a Singapore hospital. METHODS: Visual field progression was identified using Progressor software version 3.7 (Medisoft, Leeds, United Kingdom) and defined by pointwise linear regression (PLR) criteria as follows: any 2 contiguous points in the same hemifield progressing (≤-1.00 dB/year for inner points and ≤-2.00 dB/year for edge points; P < 0.01). Single nucleotide polymorphisms (SNPs) and their proxies from 10 POAG-associated loci (CAV1-CAV2, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS, PMM2, and TGFBR3-CDC7) identified from genome-wide association studies were tested for association with VF progression using logistic regression with an additive genetic model adjusting for age, gender, average intraocular pressure (IOP), central corneal thickness (CCT), and baseline vertical cup-to-disc ratio (VCDR). MAIN OUTCOME MEASURE: Visual field progression. RESULTS: Of the 1334 patients included in the study, 469 subjects (35.1%) completed 5 or more reliable VF measurements (mean follow-up, 9.01 years; standard deviation, 5.00 years). The mean age of patients was 59.6 years (standard deviation, 9.0 years); 305 patients were men and all were Chinese. The average IOP in eyes fulfilling PLR progression was 16.5 mmHg versus 17.7 mmHg in those who did not (P = 0.52). Univariate analysis revealed that increased VCDR (P = 0.003), reduced CCT (P = 0.045), and reduced superior and inferior retinal nerve fiber layer thickness (P = 0.01, respectively) were associated with VF progression. No clinical or structural features were associated significantly with VF progression on multivariate analysis. The rs1192415 index SNP in TGFBR3-CDC7 (P = 0.002; odds ratio, 6.71 per risk allele) was the only SNP associated with VF progression. CONCLUSIONS: The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with VF progression in POAG patients. These findings warrant further investigation in independent cohorts.

Angle-closure glaucoma in Asians: comparison of biometric and anterior segment parameters between Japanese and Chinese subjects.

PURPOSE: To compare anterior segment parameters in Chinese and Japanese subjects with angle closure using anterior segment optical coherence tomography (ASOCT). METHODS: One hundred and forty-two Japanese and one hundred and ninety-two Chinese subjects with primary angle closure (PAC) or primary angle-closure glaucoma (PACG) were recruited. All participants underwent A-scan biometry and ASOCT imaging (Visante, Carl Zeiss Meditec, Dublin, CA, USA). Customized software was used to measure ASOCT parameters in horizontal ASOCT scans. The parameters were compared, and multivariate analysis was performed to determine predictors of angle opening distance at 750 µm from the scleral spur (AOD750). RESULTS: Ethnic difference evaluated by multiple linear regression adjusted for age, gender, spherical equivalent, pupil diameter, and axial length showed that Japanese angle-closure subjects had significantly shallower anterior chamber depth (ACD;ß = -0.3, p < 0.001), smaller anterior chamber area (ACA; ß = -0.21, p = 0.02) and volume (ACV; ß = -0.19, p = 0.01), greater lens vault (LV, ß = 0.3, p < 0.001), lens thickness (LT; ß = 0.48, p < 0.001), greater iris area (IArea; ß = 0.19, p = 0.01), and more curved iris (ICurv; ß = 0.16, p = 0.04). The significant determinants of AOD750 were iris thickness (IT; ß = -0.21, p = 0.04), ICurv (ß = -0.17, p = 0.04), pupil diameter (PD; ß = -0.34, p = 0.001) and ACV (ß = 0.32, p < 0.001) in Japanese; and IT (ß = -0.25, p = 0.001), ACV (ß = 0.37, p < 0.001), PD (ß = -0.26, p = 0.001), and LV (ß = -0.18, p = 0.03) in Chinese. CONCLUSIONS: Compared to Chinese, Japanese angle-closure eyes have smaller and more crowded anterior segment with thicker lenses. ACV, IT, and PD are important factors for angle width in both races. These results suggest possible ethnic differences in angle-closure mechanism(s).