Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length.

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Willingness to pay for cataract surgery in baiyin district, northwestern China.

PURPOSE: To investigate willingness to pay for cataract surgery, and its associations, in Northwestern China. METHODS: Four hundred thirty-eight persons aged 50 years and above, diagnosed with cataract indicated for surgery, identified in an outreach screening program were included. Subjects were offered a willingness-to-pay interview for the maximal amount that the subjects would be willing to pay for a cataract surgery. Age, gender, literacy, education level, occupation, and annual household income were recorded. RESULTS: Among 328 (74.9%) subjects who completed the interview, 197 (60.1%) participants were willing to pay something for the cataract surgery (mean, 902.9 ± 856.7 renminbi[RMB], [US$ 145 ± 137]; median, 500RMB, US$ 78). Individuals with presenting visual acuity (PVA) in the worse eye ≤6/60 (OR: 2.1, 95% CI: 1.3-3.2) and a high annual household incomes (OR: 2.0, 95% CI: 0.9-4.6) were likely to be willing to pay for the surgery, as revealed in the regression models. Willingness to pay any amount for cataract surgery was more likely among literate persons (OR: 1.5, 95% CI: 1.0-2.4) and persons with non-agricultural occupation (OR: 1.8, 95% CI: 1.0-3.2). CONCLUSIONS: The amount that subjects were willing to pay is significantly less than the current cost of cataract surgery (5000 RMB, US$320) in the area. Providing low-cost cataract surgery to patients in a financially sustainable manner is important to increase uptake of cataract surgery among rural residents in Northwest China.

Efficacy and safety of selective laser trabeculoplasty and pattern scanning laser trabeculoplasty: a randomised clinical trial.

AIMS: To compare the intraocular pressure (IOP) lowering effect and safety profile between pattern scanning laser trabeculoplasty (PSLT) and selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) over a 12-month follow-up. METHODS: 132 patients with POAG or OHT were consecutively enrolled and randomised (1:1) to receive PSLT (n=65) or SLT (n=67) in a single centre. IOP was measured before and then on 1 day, 1 week, 1, 3, 6, 9 and 12 months after PSLT/SLT. The primary outcome measure was the proportion of patients with ≥20% IOP reduction at 12 months without IOP-lowering medications (complete success). RESULTS: The mean baseline IOP was 21.2±4.1 mm Hg for eyes randomised to PSLT and 21.3±4.7 mm Hg for eyes randomised to SLT (p=0.898). At 12 months, the IOP was 18.3±3.1 and 17.8±3.4 mm Hg, respectively (p=0.402). IOP measurements were comparable between the groups over 12 months (overall mean difference 0.4 mm Hg, 95% CI: -0.5 to 1.3 mm Hg). 15.4% of PSLT-treated and 25.4% of SLT-treated patients achieved treatment success (difference: 10.0%, 95% CI: -3.6 to 23.6) (p=0.155), respectively. A higher baseline IOP and a greater percentage of IOP reduction at day 1 were associated with a greater percentage of IOP reduction at 12 months (p<0.001). There were no significant differences in visual field mean deviation, average retinal nerve fibre layer thickness, corneal endothelial cell count and visual acuity between the treatment groups at the baseline and 12-month follow-up (p≥0.062). CONCLUSIONS: PSLT was not superior to SLT in terms of safety and IOP-lowering efficacy in patients with POAG or OHT. TRIAL REGISTRATION NUMBER: The clinical trial was registered in the Centre for Research and Biostatistics Clinical Trials Registry, the Chinese University of Hong Kong (Identifier CUHK_CCT00407). The full trial protocol can be accessed from the authors on request.

MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells.

Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.

Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury.

Retinal ganglion cell (RGC) degeneration, leading to irreversible blindness in chronic optic neuropathies, commonly begins with dendritic shrinkage followed by axon degeneration. Although limited axon regeneration in the optic nerve is possible with a genetic deletion of PTEN/SOCS3 after optic nerve injury, the roles of PTEN/SOCS3 on dendritic preservation and regeneration remain unclear. This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time-lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1 µm/day and 15.5 µm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a rate of 7.0 %/day and 7.1 %/day, respectively, and no axon regeneration in the retina was observed. RGC survival probability was higher in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice compared with Thy-1-YFP-SOCS3-/- and control mice. The differential responses between the transgenic mice demonstrate that although a genetic deletion of PTEN, SOCS3, or PTEN/SOCS3 allows partial axon regeneration in the optic nerve after optic nerve crush, a deletion of PTEN, but not SOCS3, ameliorates RGC dendritic shrinkage. This shows that the signaling pathways involved in promoting axon regeneration do not equally contribute to the preservation of dendrites, which is crucial to the translational application of neuroregenerative therapies for visual restoration.

Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.

Prevalence of visual impairment and outcomes of cataract surgery in Chaonan, South China.

PURPOSE: To estimate the prevalence and causes of blindness and visual impairment (VI), and report the outcomes of cataract surgery in Chaonan Region, Guangdong Province, southern China. DESIGN: Cross-sectional population-based survey. PARTICIPANTS: A total of 3484 participants including 1397 men (40.1%) and 2087 women (59.9%) aged ≥50 years were examined (94.2% response rate). METHOD: A two-stage cluster sampling procedure was used to select 3700 participants aged ≥50 years from 74 clusters of Chaonan Region. Participants were examined according to the Rapid Assessment of Avoidable Blindness (RAAB) method. Blindness and visual impairment (VI) were defined by the World Health Organization criteria. Participants with visual acuity (VA) < 6/18 in either eye were examined by ophthalmologists. The primary causes of blindness and VI were reported with reference to the participant's better eye. MAIN OUTCOME MEASURES: Prevalence and main causes of blindness, severe visual impairment (SVI), VI and the outcomes of cataract surgery. RESULTS: The standardized prevalence rates of blindness, SVI, and VI were 2.4% (95% confidence interval [CI], 1.9-2.9%), 1.0% (95% CI, 0.7-1.4%), and 6.4% (95% CI, 5.6%- 7.1%), respectively. The principal cause of blindness and SVI was cataract, accounting for 67.1% and 67.6% respectively, and the principal cause of VI was refractive error (46.9%). One hundred and fifty five out of 3484 (4.4%) people (211 eyes) had cataract surgery. Of the 211 eyes that had cataract surgery, 96.7% were pseudophakic. 67.2% of the 211 operated eyes had a presenting visual acuity (PVA) of 6/18 or better. CONCLUSIONS: The prevalence of blindness, SVI, and VI was high among rural residents in Chaonan. Cataract remained the leading cause of avoidable blindness. Outcomes of cataract surgery performed in rural private clinics were suboptimal. Quality-control initiatives such as hands-on training program should be introduced to improve cataract surgery outcomes.

Relevant variations and neuroprotecive effect of hydrogen sulfide in a rat glaucoma model.

Glaucoma is an irreversible and blinding neurodegenerative disease of the eye, and is characterized by progressive loss of retinal ganglion cells (RGCs). Since endogenous hydrogen sulfide (H2S) was reported to be involved in neurodegeneration in the central nervous system, the authors aimed to develop a chronic ocular hypertension (COH) rat model simulating glaucoma and therein test the H2S level together with the retinal protein expressions of related synthases, and further investigated the effect of exogenous H2S supplement on RGC survival. COH rat model was induced by cross-linking hydrogel injection into anterior chamber, and the performance of the model was assessed by intraocular pressure (IOP) measurement, RGC counting and retinal morphological analysis. Endogenous H2S level was detected along with the retinal protein expressions of H2S-related synthases cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in the COH rats. Retinal H2S level and RGC survival were evaluated again after NaHS (a H2S donor) treatment in the COH rats. The results showed that the COH model succeeded in simulating glaucoma features, and retinal H2S level decreased significantly when the retinal protein expressions of CBS, CSE and 3-MST were downregulated generally in the COH rats. Furthermore, the decrease of retinal H2S level and loss of RGCs were both improved by NaHS treatment in experimental glaucoma, without obvious variation of IOP. Our study revealed that the intracameral injection of cross-linking hydrogel worked efficiently in modeling glaucoma, and H2S had protective effect on RGCs and might be involved in the pathological mechanism of glaucomatous neuropathy.

Barriers for poor cataract surgery uptake among patients with operable cataract in a program of outreach screening and low-cost surgery in rural China.

AIMS: To identify the reasons for poor uptake of cataract surgery in a program of outreach screening and low-cost surgery in Pucheng County, a rural area in northwestern China. METHODS: Detailed interviews with a semi-structured questionnaire were conducted by telephone or face-to-face for participants who had been advised to attend a low-cost cataract surgery program but did not schedule the surgery within 3 months after the initial screening. RESULTS: Among 432 eligible subjects, 355 (82.2%) were interviewed (mean age 70.6 ± 6.6 years, 73.8% female). A total of 138 subjects (38.9%) were interviewed by phone and 217 (61.1%) were interviewed face-to-face. Lack of family support (n = 106, 29.9%) and failure to understand the need for surgery (n = 96, 27.0%) were the two main reasons for not undergoing cataract surgery. Other factors included fear of surgery (n = 62, 17.5%), lack of faith in doctors (n = 36, 10.1%), financial constraints (n = 25, 7.0%) and lack of transportation (n = 4, 1.1%). CONCLUSION: The principal barriers to low-cost cataract surgery uptake in rural China included lack of family support and failure to understand the need for surgery. Education targeting entire families to eliminate these barriers and development of community support systems at the family level are required to achieve greater uptake of low-cost cataract surgery programs in rural China.

Analysis of bleb morphology after trabeculectomy with Visante anterior segment optical coherence tomography.

BACKGROUND: To describe the use of anterior segment optical coherence tomography (OCT) in imaging intrableb morphology after trabeculectomy. METHODS: 14 post-trabeculectomy eyes from 11 primary open angle glaucoma and 3 primary angle closure glaucoma subjects were studied. The blebs were classified with reference to slit lamp morphology and bleb function. They included diffuse filtering (n = 7), cystic (n = 2), encapsulated (n = 2) and flattened (n = 3) bleb types. One eye in each patient was imaged with the Visante anterior segment OCT. A vertical scan line of 10 mm consisting of 512 A-scans was positioned at the centre of the bleb. The images were then analysed by built-in software. Intrableb morphologies and structures, including bleb wall thickness, subconjunctival fluid collections, suprascleral fluid space, scleral flap thickness, intrableb intensity (low, medium or high) and the route under the scleral flap were characterised and measured. RESULTS: Diffuse filtering blebs were found by subconjunctival fluid collections. Suprascleral fluid space and the route under the scleral flap were identified in four of the seven cases. Cystic blebs were composed of a large hyporeflective space with multiloculated fluid collections covered by a thin layer of conjunctiva. Encapsulated blebs had a thick bleb wall with high reflectivity and an enclosed fluid filled space. Flattened blebs demonstrated high scleral reflectivity and no bleb elevation. CONCLUSIONS: Visante anterior segment OCT can be used for bleb imaging. The different patterns of intrableb morphology identified by OCT were related to slit lamp appearance and bleb function. This information may be useful to study the different surgical outcomes and the process of wound healing in trabeculectomised eyes.