Glaucoma Control Research Articles

Plasma levels of sirtuin and adiponectin in patients with primary open-angle glaucoma, exfoliative glaucoma, and healthy controls.

To compare plasma levels of sirtuin 1 (SIRT1) and adiponectin (APN) in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), and healthy control subjects. This prospective case-control study collected plasma samples from 118 participants. All subjects underwent a comprehensive ophthalmologic examination before the acquisition of a plasma sample. Plasma samples were obtained from 40 POAG, 38 XFG, and 40 healthy control subjects without any evidence of systemic or ocular disease. Serum SIRT1 and APN levels were estimated by an enzyme-linked immunosorbent assay, ELISA (Elabscience, Houston, USA) method. Statistical analysis of results relied on Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square, analysis of variance (ANOVA) tests, and linear regression analysis, where appropriate. A significant decrease in SIRT1 levels was observed in POAG patients compared to healthy controls (p = 0.004, Dunn's test). In contrast, no difference was detected between XFG and POAG patients or healthy controls (p = 0.32 and p = 0.34, respectively, Dunn's test). There was no significant difference in plasma APN levels between the three groups under investigation (p = 0.59, ANOVA). Alterations in serum level of SIRT1 may suggest a possible role in POAG via potential effects in neuroprotection and oxidative stress.

PERG adaptation for detection of retinal ganglion cell dysfunction in glaucoma: a pilot diagnostic accuracy study

It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-min presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls. In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 min (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects. PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude and phase were significantly different in patients compared to controls (p < 0.01), whereas phase angular dispersion was greater in patients but not significantly different between the two groups. The area under the ROC curves were 0.87 and 0.76 for PERGx amplitude slope and grand-average vector amplitude, and 0.62 and 0.87 for PERGx angular dispersion and grand-average vector phase, respectively. The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional retinal ganglion cell autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.

Comparison of peripapillary and macular vascular density in primary open-angle glaucoma, pseudoexfoliation glaucoma, and normal control eyes

PurposeTo compare the optical coherence tomography angiography (OCT-A) of the macula, and optic disc in primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PXG), and normal eyes. MethodsIn this observational, cross-sectional study, Sixty–five eyes with POAG, 61 eyes of age, and mean deviation (MD) from standard automated perimetry matched PXG patients, and 45 normal control eyes underwent OCT-A using AngioVue, and optic disc-associated vessel density (VD), macular-associated VD, Foveal avascular zone (FAZ) area, FAZ perimeter (PERIM), and vessel density within a 300 μm wide region of the FAZ (FD) were compared between groups. ResultsPeripapillary OCT-A parameters were significantly different among normal, and glaucomatous eyes with the highest values in the control eyes, but none of the peripapillary OCT-A parameters except inside disc VD was statistically significantly different between the PXG eyes, and POAG eyes. Correlation analysis revealed significant correlation between mean retinal nerve fiber layer (RNFL) and peripapillary VD in control (r = 0.427, P = 0.006), PXG (r = 0.82, P<0.001), and POAG (r = 0.79, P<0.001) eyes.PXG eyes exhibited significantly lower superficial, and deep macular vessel densities in parafoveal and perifoveal regions compared with POAG eyes after adjustment (p<= 0.05). Overall, moderate /severe PXG eyes had lower superficial, and deep vessel densities in parafoveal and perifoveal regions compared to mild PXG. ConclusionPeripapillary VD (inside disc), and macular vessel densities (parafovea and perifovea) demonstrate a significant difference in age and glaucoma severity-matched POAG and PXG eyes. Moderate/advance glaucomatous eyes, exhibit significant damage to the superficial and deep macular vascular structures.

Patient-Reported Symptoms Demonstrating an Association with Severity of Visual Field Damage in Glaucoma

To determine which patient-reported symptoms best distinguish patients with and without glaucoma and explain the most variance in visual field (VF) damage and to compare the amount of variance that can be explained by symptoms versus retinal nerve fiber layer (RNFL) thickness. Cross-sectional study. Adults diagnosed with glaucoma or suspicion of glaucoma (controls). Worse-eye VF damage was defined on the basis of perimetric testing. Thickness of RNFL was defined by OCT imaging. Patients rated their visual symptoms on questions collated from several published questionnaires, rating the frequency and severity of 28 symptoms on a scale of 1 (never/not at all) to 4 (very often/severe). Multivariable regression models identified patient-reported symptoms that contributed the highest variance in VF damage. Patient-reported symptoms that explained the most variance in VF damage and amount of variance in VF damage explained by patient-reported symptoms and RNFL. A total of 170 patients (mean age: 64 years; 58% female; 47% employed) completed testing, including 95 glaucoma suspects and 75 glaucoma patients. In glaucoma patients, median mean deviation of VF damage in the worse eye was-19.3 and ranged from-5.3 to-34.7 decibels. Symptoms more common among glaucoma patients compared with glaucoma suspects included better vision in 1 eye, blurry vision, glare, sensitivity to light, cloudy vision, missing patches of vision, and little peripheral vision. Worse severity ratings for the symptom "little peripheral vision" explained the most variance in VF damage (43%). A multivariable model including the frequency of cloudy vision, severity of having little peripheral vision, missing patches, 1 eye having better vision, and vision worsening, plus sociodemographic features, explained 62% of the variance in VF damage. Comparatively, a multivariable model of worse-eye RNFL thickness and sociodemographic features explained 42% of the variance in VF damage, whereas a model including only sociodemographic features explained 8% of the variance in VF damage. Five patient-reported symptoms explain a significant amount of the variance in VF damage. Asking patients about their symptoms may optimize patient-physician communication and be a useful adjunct to clinical testing in some patients to estimate disease severity.

Vessel Evaluation in Patients with Primary Open-Angle Glaucoma, Normal Tension Glaucoma and Healthy Controls.

PurposeTo compare changes in central retinal arterial equivalent (CRAE), central retinal vein equivalent (CRVE), arteriovenous ratio (AVR), tortuosity and fractal dimension in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) and in a control group (CG) on fundus photographs. Further, to provide further evidence of vascular change in glaucoma patients using a novel method of tortuosity.Patients and MethodsThe primary endpoint was the change in CRAE, CRVE, AVR, fractal dimension and tortuosity of the retinal vasculature from baseline, retrospectively analyzed from 2011 to 2017 at the University Eye Hospital Tuebingen. Fundus photos of POAG (N = 49), NTG (N = 38) and CG (N = 18) were computer evaluated and analyzed in the quantities mentioned above.ResultsCRAE in NTG and POAG and CRVE in NTG significantly decreased (P = 0.02, P = 0.01; P = 0.03) whereas CRVE in POAG increased insignificantly (P = 0.72). In NTG, AVR decreased significantly (P = 0.05), but to a lesser extent than in POAG (P < 0.001). In CG, CRAE decreased insignificantly (P = 0.10), CRVE decreased significantly (P = 0.03) and AVR increased insignificantly (P = 0.77). In POAG tortuosity calculated using standard methods as well as our novel method, increased significantly (P = 0.015–0.04), whereas it did not occur in NTG (P = 0.18–0.57) and CG (P = 0.11–0.21). Fractal dimensions in POAG decreased significantly (P = 0.001–0.002), whereas in NTG and CG changes were insignificant (P = 0.33–0.92).ConclusionBased on a retrospective analysis of fundus photographs, specific retinal vasculature features of the retinal vasculature display significant alterations associated with NTG and POAG. The assessment of tortuosity using our novel method was consistent with previously established methods for analyzing tortuosity.

Corneal Structural Changes in Congenital Glaucoma.

To identify corneal structure differences on quantitative high-frequency ultrasound biomicroscopy (UBM) among subjects with congenital glaucoma compared with controls. This prospective case-control study evaluated 180 UBM images from 44 eyes of 30 subjects (18 control and 12 glaucoma, mean age 5.2±8.0 years, range 0.2-25.8 years) enrolled in the Pediatric Anterior Segment Imaging and Innovation Study (PASIIS). ImageJ was used to quantify a comprehensive set of corneal structures according to 21 quantitative parameters. Statistical analysis compared corneal measurements in glaucoma subtypes and age-matched controls with significance testing and mixed effects models. Significant differences between congenital glaucoma cases and controls were identified in 16 of 21 measured parameters including angle-to-angle, central and peripheral corneal thicknesses, scleral integrated pixel density, anterior corneal radius of curvature, and posterior corneal radius of curvature. Eight parameters differed significantly between primary congenital glaucoma and glaucoma following congenital cataract surgery. Multiple measurable corneal structural differences exist between congenital glaucoma and control eyes, and between primary and secondary congenital glaucoma, including but not limited to corneal width and thickness. The structural differences can be quantified from UBM image analysis. Further studies are needed to determine whether corneal features associated with glaucoma can be used to diagnose or monitor progression of congenital glaucoma.

Assessment of the Role and Timing of Glaucoma Surgery in Boston Keratoprosthesis Type 1 Patients

To determine the role and optimal timing of glaucoma surgery in relation to Boston keratoprosthesis type 1 (KPro) implantation. Retrospective, comparative, nonrandomized clinical study. Single-center study of a total of 100 eyes (100 patients) implanted with a KPro between 2008 and 2017, and diagnosed with glaucoma before or after KPro. Patients were separated into 2 groups: those with preexisting glaucoma and those who developed de novo glaucoma after KPro. Groups were then divided based on whether patients were medically or surgically managed. Glaucoma surgery included glaucoma drainage device (GDD) implantation, trabeculectomy, and cyclophotocoagulation (CPC). Primary outcomes included best-corrected visual acuity (BCVA), glaucoma progression, and complications. Differences in outcomes were compared using parametric and nonparametric tests, as well as log-rank test to compare time-to-outcome events. Among 72 eyes with preexisting glaucoma, 27 (38%) had glaucoma surgery before KPro (18 GDD), whereas 45 (62%) were medically managed only. Among the latter, 19 (42%) needed glaucoma surgery post-KPro (16 GDD). Among 28 eyes with de novo glaucoma, 12 (43%) had glaucoma surgery post-KPro (9 GDD). For eyes with preexisting glaucoma, glaucoma progression was greater with glaucoma surgery performed post-KPro (100%) compared with pre-KPro (74%, P=.016) and to medical management (54%, P=.002). No increase in complications were observed with glaucoma surgery compared to medications only (P > .05), whereas fewer eyes maintained a BCVA of 20/200 or better over time with medical management (P=.013). Eyes with de novo glaucoma had similar progression, BCVA, and complications between medical and surgical care (P > .05). Glaucoma surgery should be performed before or at the same time as KPro implantation in eyes with preexisting glaucoma. Complication rates are not increased when glaucoma surgery is performed in KPro eyes with either preexisting or de novo glaucoma. To ensure optimal glaucoma control, glaucoma surgery should be performed as early as possible in KPro eyes with good visual potential.

Glare and Mobility Performance in Glaucoma: A Pilot Study.

Glare disability affects patients with moderate and severe glaucoma. Under glare conditions, mobility performances of glaucoma patients are reduced. The aim of this study was to evaluate glare disability and its impact on mobility and orientation in glaucoma patients. Twenty-two glaucoma patients and 12 age-matched control subjects were included. All patients underwent a clinical evaluation of visual function and halo size measurements to determine glare disability with a glare score (GS) of the best eye and worse eye. Mobility was evaluated by 4 mobility courses on an artificial street (StreetLab) under photopic conditions (P) and mesopic conditions with an additional light source in front of the patient to mimic dazzling conditions (M+G). Mobility time, mobility incidents, trajectory segmentation, distance traveled, preferred walking speed on trial (WS) and percentage of preferred walking speed (PPWS) were recorded, and the Nasa task load index (Nasa-TLX) was evaluated. GS of the worse eye and GS of the best eye were significantly higher in glaucoma patients than in the control group (P=0.001 and 0.003). It was significantly different between moderate glaucoma patients and controls (P=0.001 and 0.010, respectively) and between severe glaucoma patients and controls (P=0.049 and 0.016). In locomotion tasks, comparing performance under M+G and P conditions, mobility performance was significantly different concerning mobility time (P=0.010), distance traveled (P=0.008), WS (P=0.007), PPWS (P=0.006), and Nasa-TLX (P=0.017) in the glaucoma group. Under M+G lighting conditions, mobility performance for glaucoma patients was significantly worse than controls with regard to WS (P=0.038), PPWS (P=0.0498), mobility time (P=0.046), and Nasa-TLX (P=0.006). Glare disability was observed in patients with moderate and severe glaucoma and had an impact on their mobility performance.

Mapping Visual Field Defects With fMRI - Impact of Approach and Experimental Conditions.

Current initiatives to restore vision emphasize the need for objective assessments of visual field (VF) defects as pursued with functional magnetic resonance imaging (fMRI) approaches. Here, we compared population receptive field (pRF) mapping-based VF reconstructions to an fMRI method that uses more robust visual stimulation (on-off block design) in combination with individualized anatomy-driven retinotopic atlas-information (atlas-based VF). We investigated participants with sizable peripheral VF-deficits due to advanced glaucoma (n = 4) or retinitis pigmentosa (RP; n = 2) and controls (n = 6) with simulated scotoma. We obtained (1) standard automated perimetry (SAP) data as reference VFs and 3T fMRI data for (2) pRF-mapping [8-direction bar stimulus, fixation color change task] and (3) block-design full-field stimulation [8-direction drifting contrast patterns during (a) passive viewing (PV) and (b) one-back-task (OBT; reporting successions of identical motion directions) to probe the impact of previously reported task-related unspecific visual cortex activations]. Correspondence measures between the SAP and fMRI-based VFs were accuracy, assisted by sensitivity and specificity. We found an accuracy of pRF-based VF from V1 in patients [median: 0.62] that was similar to previous reports and increased by adding V2 and V3 to the analysis [0.74]. In comparison to the pRF-based VF, equivalent accuracies were obtained for the atlas-based VF for both PV [0.67] and, unexpectedly, the OBT [0.59], where, however, unspecific cortical activations were reflected by a reduction in sensitivity [0.71 (PV) and 0.35 (OBT)]. In conclusion, in patients with peripheral VF-defects, we demonstrate that previous fMRI procedures to obtain VF-estimates might be enhanced by: (1) pooling V1-V3 to enhance accuracy; (2) reporting sensitivity and specificity measures to increase transparency of the VF-reconstruction metric; (3) applying atlas-based procedures, if pRF-based VFs are not available or difficult to obtain; and (4) giving, counter-intuitively, preference to PV. These findings are expected to provide guidance to overcome current limitations of translating fMRI-based methods to a clinical work-up.

Prevalence of Ocular Surface Disorder and Dry Eye in Patients with Glaucoma using Topical Antiglaucoma Medications

Background: The main aim of the study is to establish the prevalence of ocular surface disorders in glaucoma patients treated with topical antiglaucoma medications. Methods: Investigation of 50 eyes of 25 patients has been performed using two or more antiglaucoma medications for six months, and compared with 50 eyes of 25 normal subjects without any ocular problem. After one year each patient was evaluated by Schirmer’s (SCH) test-I Tear break-up time (TBUT), Corneal staining score. Results: The mean values in the glaucoma cases and control groups respectively were as follows: Schirmer’s test-1 (7.63 ± 2.64mm / 12.86 ± 1.93mm; p= 0.001), Tear breakup time (9.44 2 ±.76 sec / 11.8 ± 1.88 sec; p=0.001), Corneal staining score (5.7 ± 2.33 /1.1 ± 0.58; p=0.001). Conclusion: Patients on antiglaucoma therapy have a greater prevalence of ocular surface disease and dry eye. The causative factors were medications with preservatives and longer treatment duration. Keywords: Antiglaucoma medication, dry eye, ocular surface diseases (OSD), Schirmer’s (SCH) test, Tear breakup time, Corneal staining score.

Comparison of Choroidal Vascularity Index in Patients with Pseudoexfoliation Glaucoma, Pseudoexfoliation Syndrome, and Healthy Controls

ABSTRACT Purpose To compare peripapillary choroidal vascularity index (CVI) parameters in pseudoexfoliation glaucoma (PEG), pseudoexfoliation (PEX) syndrome, and healthy controls. Methods A total of 240 eyes of 240 patients were included in this cross-sectional prospective study, and the three groups consisted of (i) 80 eyes of 80 patients with PEG, (ii) 80 eyes of 80 patients with PEX syndrome, and (iii) 80 healthy control eyes. Peripapillary enhanced depth imaging optical coherence tomography images were binarized via standard protocols with the ImageJ software. CVI was analyzed in all sectors of the peripapillary region. Results Peripapillary CVI was found to be significantly lower in the PEG group (61.6 ± 2.32) compared with the PEX group (64.7 ± 3.15) and the control group (67.5 ± 2.44) (p < .001), and patients with PEX also had significantly lower values compared to controls (p < .001). Peripapillary CVI values were significantly lower in the temporal, nasal, superotemporal, superonasal, inferotemporal and inferonasal sectors of the PEG group compared to both the PEX group and controls (p < .001). Peripapillary CVI was also found to be lower in all sectors in the PEX group compared to controls (p < .001). Global peripapillary choroidal thickness was significantly thinner in the PEG group than the PEX and control groups (133.37 ± 39.16, 154.36 ± 33.28 and 157.82 ± 36.77 μm, respectively, p < .001). Conclusions In the current study, it was shown that the presence of PEX caused a decrease in CVI value and this decrease was highest in patients with PEG. CVI may be a useful parameter to show vascular dysfunction in PEG and PEX syndrome.

Development of Primary Open Angle Glaucoma-Like Features in a Rhesus Macaque Colony From Southern China.

PurposeTo describe the ocular phenotype of spontaneous glaucoma in a non-human primate colony.MethodsIn total, 722 Rhesus macaque monkeys aged 10 to 25 years underwent optical coherence tomography (OCT), fundus photography (FP), and intraocular pressure (IOP) measurements. Monkeys with baseline cup-to-disc ratio (CDR) <0.5 were used to establish baseline ocular features. A subset was followed longitudinally for three years and compared to glaucoma suspects on the basis of OCT/FP criteria.ResultsThe average IOP under ketamine sedation and average CDR for the entire colony was 13.0 ± 4.3 mm Hg and 0.38 ± 0.07, respectively. The mean baseline conscious IOP of glaucoma suspects (N = 18) versus controls (N = 108) was 16.2 ± 3.5 mm Hg and 13.9 ± 2.3 mm Hg, respectively (P = 0.001). All glaucoma suspects had unremarkable slit lamp examinations and open angles based on anterior segment OCT. Baseline global circumpapillary retinal nerve fiber layer (RNFL) thickness was 91.5 ± 11.0 µM versus 102.7 ± 8.5 µM in suspects and controls, respectively (P < 0.0001). All sectors on the baseline circumpapillary OCT showed a significant reduction in RNFL thickness versus controls (P ≤ 0.0022) except for the temporal sector (P ≥ 0.07). In three-year longitudinal analysis, neither CDR nor OCT parameters changed in controls (N = 40; P ≥ 0.16), whereas significant increase in CDR (P = 0.018) and nominally significant decreases in two OCT sectors (nasal, P = 0.023 and nasal inferior, P = 0.046) were noted in suspects.ConclusionsMembers of a nonhuman primate colony exhibit important ophthalmic features of human primary open-angle glaucoma.Translational RelevanceIdentification of a spontaneous model of glaucoma in nonhuman primates represents an unprecedented opportunity to elucidate the natural history, pathogenesis and effective therapeutic strategies for the disease.

Central retinal vascular trunk deviation in unilateral normal-tension glaucoma.

To investigate whether the position of the central retinal vascular trunk (CRVT), as a surrogate of lamina cribrosa (LC) offset, was associated with the presence of glaucoma in normal-tension glaucoma (NTG) patients. The position of the CRVT was measured as the deviation from the center of the Bruch's membrane opening (BMO), as delineated by spectral-domain optical coherence tomography imaging. The offset index was calculated as the distance of the CRVT from the BMO center relative to that of the BMO margin. The angular deviation of CRVT was measured with the horizontal nasal midline as 0° and the superior location as a positive value. The offset index and angular deviation were compared between glaucoma and fellow control eyes within individuals. NTG eyes had higher baseline intraocular pressure (P = 0.001), a larger β-zone parapapillary atrophy area (P = 0.013), and a larger offset index (P<0.001). In a generalized linear mixed-effects model, larger offset index was the only risk factor of NTG diagnosis (OR = 31.625, P<0.001). A generalized estimating equation regression model revealed that the offset index was larger in the NTG eyes than in the control eyes for all ranges of axial length, while it was the smallest for the axial length of 23.4 mm (all P<0.001). The offset index was larger in the unilateral NTG eyes, which fact is suggestive of the potential role of LC/BMO offset as a loco-regional susceptibility factor.

Minimally Invasive Glaucoma Surgical Techniques for Open-Angle Glaucoma

Glaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients. To summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews. The Cochrane Database of Systematic Reviews including studies published before June 1, 2021. Reviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted. The proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up. Six eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results. Based on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.

Eyes of Africa: The Genetics of Blindness: Study Design and Methodology

BackgroundThis report describes the design and methodology of the “Eyes of Africa: The Genetics of Blindness,” a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health.Methods This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing.Discussion A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.

Brain-derived Neurotrophic Factor in the Aqueous Humor of Glaucoma Patients.

Brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of glaucoma. BDNF concentrations reported in previous studies have varied widely, and the concentration of BDNF in aqueous humor is unknown. In this study, BDNF concentrations in the aqueous humor of glaucoma patients and control patients were measured with ELISA kits. This prospective, observational study examined BDNF levels in aqueous humor in 62 eyes of 43 patients who underwent cataract surgery or trabeculectomy (11 glaucoma patients and 32 non-glaucoma cataract patients as controls). BDNF concentrations were examined by 4 different enzyme-linked immunosorbent assay (ELISA) techniques. The mean ± SD patient age was 72.0 ± 10.1 (range 35 to 87) years. Two of the techniques detected no BDNF in aqueous humor in any samples (n=3 and n=9, respectively); the average value was less than zero. An ultrasensitive ELISA kit did not yield reliable measurements. Finally, in an even more sensitive ELISA (Simoa-HD1), performed by an outside contractor, 25 (54.3%) eyes were below the detection limit, including 20 (55.6%) control and 5 (50%) glaucoma cases. For eyes with detectable BDNF, the overall BDNF concentration was 0.158 pg/mL (n=21): 0.196 pg/mL (n=16) in controls and 0.034 pg/mL (n=5) in glaucoma cases. BDNF level in aqueous humor varies widely.

Correlation Analysis between Macular Choroidal Thickness and Visual Field Mean Defect in Primary Open-Angle Glaucoma.

Purpose To evaluate the differences in macular choroidal thickness and volume between patients with primary open-angle glaucoma (POAG) and healthy controls to assess the correlation between macular choroidal thickness and visual field mean defect (MD). Methods Case-control study. A total of 101 patients (101 eyes) with POAG who were hospitalized in our hospital and 102 healthy subjects (102 eyes) matched by age, sex, and axial length were consecutively selected as the POAG group and the control group, respectively. The macular choroidal thickness and volume in nine regions were measured in all subjects by enhanced-depth imaging optical coherence tomography (EDI-OCT). Results The mean thicknesses of the choroid in the macular area in the POAG group and healthy group were 207.97 ± 62.83 µm and 208.24 ± 47.97 µm, and the mean volumes were 0.63 ± 0.19 µm3 and 0.64 ± 0.14 µm3. There were no significant differences in macular choroidal thickness, volumes of various macular regions, or mean choroidal thickness or volume between the POAG and healthy groups (all p > 0.05). The macular choroidal thickness of various macular regions was not correlated with visual field MD in the POAG group (all p > 0.05). Conclusion The macular choroidal thicknesses and volumes in POAG patients were not significantly different from those in healthy individuals. The macular choroidal thickness was not correlated with MD in POAG patients. Therefore, macular choroidal thickness is not an appropriate parameter to evaluate damage caused by POAG, and the role of the macular choroid thickness in POAG needs to be further investigated.

Dry eye disease among Glaucoma patients on topical hypotensive medications, in a tertiary hospital, Ethiopia

BackgroundDry eye disease is a multifactorial disease; causing various ocular symptoms with potential damage to the ocular surface. Applying hypotensive eye drops are presumed to initiate or exacerbate existing dry eye disease. The purpose of this study was to determine the frequency of signs and symptoms and severity of dry eye disease among glaucoma patients on topical hypotensive medications and controls.MethodsA cross-sectional comparative study, involving 320 glaucoma patients and controls. Ocular Surface Disease Index (OSDI) symptoms score and Schirmer, tear breakup time and corneal staining tests were used to assess dry eye disease. Data was analyzed using SPSS version 24 software; p-value less than 0.05 was considered as statistically significant.ResultsAmong the 160 study glaucoma patients, the mean duration of topical hypotensive medication use was 5.2 ± 5.21 years (range, 4 months - 32 years). Mild to severe level of OSDI score was found in 122 (76%) glaucoma patients and in 137 (86%) controls (p = 0.033). Mild to sever abnormal clinical tests in the glaucoma patients and control, respectively, were 106 (66%) vs 80 (50%) corneal staining (p = 0.045), 79 (49%) vs 72 (45%) TBUT (p = 0.021), and 91 (57%) vs 83 (52%) Schirmer test (p = 0.242). Test results at the level of sever: 2 (1%) vs 0 (0%) corneal staining, 50 (31%) vs 39 (24%) TBUT and 65 (41%) vs 60 (38%) Schirmer test in the glaucoma patents and controls, respectively. Corneal staining and TBUT had correlation with the number of drugs (p = 0.004 and 0.031, respectively), and more relationship of the two tests with total number of drops applied per day (p = 0.01 and p < 0.001, respectively). Patients on pilocarpine and timolol had more corneal staining and lower TBUT [(p = 0.011 and p < 0.001) and (p = 0.04 and 0.012), respectively].ConclusionsThe study has identified glaucoma patients to be more affected by dry eye disease than non-glaucoma patients, and presence of significantly lower TBUT and higher corneal staining in the glaucoma patients on multidrops and multidose per day. We recommend consideration of evaluation and management of DED for glaucoma patients on multidrops and multidose hypotensive medications.

Sub-foveal choroidal thickness in both eyes of patients with unilateral primary open-angle glaucoma and related influencing factors

Objective: To investigate and compare the sub-foveal choroidal thickness (SFCT) in both eyes of patients with unilateral primary open-angle glaucoma (POAG) and healthy controls. Methods: Cross-sectional study. Patients with unilateral POAG and healthy controls were recruited from September 2018 to September 2019 in the Beijing Tongren Hospital. All subjects underwent enhanced depth imaging optical coherence tomography. The SFCT was measured at the fovea, and at 500 μm, 1 000 μm and 2 000 μm nasal and temporal to the fovea. Paired t test was conducted to compare the choroidal thickness between affected POAG eyes and unaffected fellow eyes. Analysis of covariance was conducted to compare the choroidal thicknesses between POAG eyes and controls. Multiple regression analysis determined the association between choroidal thickness and age, gender, spherical equivalent and mean deviation. Results: Seventy-five patients with unilateral POAG (mean age, 46 years; 48 males, 27 females) and 61 healthy controls (mean age, 44 years; 34 males, 27 females) were included in this study. The SFCT of POAG eyes was (244.41±83.18) μm, which was not significantly different from their unaffected fellow eyes [(254.28±88.92) μm, P>0.05] and controls (right eyes) [(272.98±55.87) μm, P>0.05]. Choroidal thickness at 2 000 μm nasal to the fovea was significantly decreased in the glaucomatous eyes compared with the unaffected fellow eyes [(167.84±70.44) vs. (188.84±89.06) μm, t=-3.55; P<0.01]. There were no significant differences among the glaucomatous eyes, unaffected fellow eyes and healthy controls in choroidal thickness at 500 μm and 1 000 μm nasal and temporal to the fovea, as well as at 2 000 μm temporal to the fovea (all P>0.05). The SFCT of POAG eyes was associated with mean deviation (β=14.66, P<0.05) and spherical equivalent (β=14.95, P<0.01) but not with age and gender (both P>0.05). Conclusions: The SFCT of affected eyes in patients with unilateral POAG has no significant difference from unaffected fellow eyes and healthy controls. However, the choroidal thickness at 2 000 μm nasal to the fovea is thinner in the POAG eyes as compared with the fellow eyes. A thinner SFCT is correlated with the loss of visual field and a higher spherical equivalent in myopia. This may suggest a contributing role of the perfusion of the choroid in the pathogenesis of glaucoma. (Chin J Ophthalmol, 2021, 57: 194-200).

Five-year results of non-penetrating deep sclerectomy with demineralized cancellous bone xenogenically derived collagen glaucoma implant.

To investigate the long-term effectiveness of non-penetrating deep sclerectomy (NPDS) with xenogenically derived cancellous bone collagen glaucoma implant (XCB-CGI) implantation in patients with primary open-angle glaucoma (POAG). Retrospective chart review of patients with POAG stages 2 and 3 was treated with NPDS and XCB-CGI. Follow-up was at 6months, 1, 2, 3, 4 and 5years after surgery. Main outcomes were intraocular pressure (IOP) and medication burden. Secondary outcomes were visual acuity, corneal hysteresis (CH), visual field (VF) and optical coherence tomography (OCT) parameter analysis. Among 71 patients (71 eyes), the mean age was 72.7 ± 9.8. Average initial IOP was 27.7 ± 7.9 and average initial med load was 2.36 ± 0.99. At 6months, 1, 2, 3, 4 and 5years, the average IOP was 14.9 ± 3.3mm Hg (46.2% reduction), 15.3 ± 4.0mm Hg (44.7% reduction), 14.2 ± 3.8mm Hg (48.7% reduction), 15.2 ± 3.3mm Hg (45.0% reduction), 15.5 ± 3.3mm Hg (44.0% reduction) and 14.2 ± 2.8mm Hg (48.7% reduction), respectively. In 5years, the success rate was 34% and 67%, without, and with medications (1.8 ± 0.8 meds required), respectively. Visual acuity was not significantly different (P > .05) at all follow-up visits from baseline. Mean CH increased by 2.1 ± 0.8 (P = .05). No glaucomatous deterioration of the VF and OCT parameters was detected in 56 eyes at the 5-year follow-up. NPDS with XCB-CGI implantation is an effective procedure to normalize the level of IOP, stabilize glaucomatous changes and decrease the number of meds needed for glaucoma control.