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Saini C, Jiang S, Devlin J, Pan L, Tang Y, Tang J, Sun JA, Lorenzo MM, Wang Q, Pasquale LR, Cho K-S, Chen DF, Shen LQ.
Association between HSP-Specific T-Cell Counts and Retinal Nerve Fiber Layer Thickness in Patients with Primary Open-Angle Glaucoma. Ophthalmol Sci 2023;3(3):100310.
AbstractOBJECTIVE: Previous laboratory reports implicate heat shock protein (HSP)-specific T-cell responses in glaucoma pathogenesis; here, we aimed to provide direct clinical evidence by correlating systemic HSP-specific T-cell levels with glaucoma severity in patients with primary open-angle glaucoma (POAG). DESIGN: Cross-sectional case-control study. SUBJECTS: Thirty-two adult patients with POAG and 38 controls underwent blood draw and optic nerve imaging. METHODS: Peripheral blood monocytes (PBMC) were stimulated in culture with HSP27, α-crystallin, a member of the small HSP family, or HSP60. Both interferon-γ (IFN-γ)+ CD4+ T helper type 1 cells (Th1) and transforming growth factor-β1 (TGF-β1)+ CD4+ regulatory T cells (Treg) were quantified by flow cytometry and presented as a percentage of total PBMC counts. Relevant cytokines were measured using enzyme-linked immunosorbent assays. Retinal nerve fiber layer thickness (RNFLT) was measured with OCT. Pearson's correlation (r) was used to assess correlations. MAIN OUTCOME MEASURES: Correlations of HSP-specific T-cell counts, and serum levels of corresponding cytokine levels with RNFLT. RESULTS: Patients with POAG (visual field mean deviation, -4.7 ± 4.0 dB) and controls were similar in age, gender, and body mass index. Moreover, 46.9% of POAG and 60.0% of control subjects had prior cataract surgery (P = 0.48). Although no significant difference in total nonstimulated CD4+ Th1 or Treg cells was detected, patients with POAG exhibited significantly higher frequencies of Th1 cells specific for HSP27, α-crystallin, or HSP60 than controls (7.3 ± 7.9% vs. 2.6 ± 2.0%, P = 0.004; 5.8 ± 2.7% vs. 1.8 ± 1.3%, P < 0.001; 13.2 ± 13.3 vs. 4.3 ± 5.2, P = 0.01; respectively), but similar Treg specific for the same HSPs compared with controls (P ≥ 0.10 for all). Concordantly, the serum levels of IFN-γ were higher in POAG than in controls (36.2 ± 12.1 pg/ml vs. 10.0 ± 4.3 pg/ml; P < 0.001), but TGF-β1 levels did not differ. Average RNFLT of both eyes negatively correlated with HSP27- and α-crystallin-specific Th1 cell counts, and IFN-γ levels in all subjects after adjusting for age (partial correlation coefficient r = -0.31, P = 0.03; r = -0.52, p = 0.002; r = -0.72, P < 0.001, respectively). CONCLUSIONS: Higher levels of HSP-specific Th1 cells are associated with thinner RNFLT in patients with POAG and control subjects. The significant inverse relationship between systemic HSP-specific Th1 cell count and RNFLT supports the role of these T cells in glaucomatous neurodegeneration. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.
Scelfo C, ElSheikh RH, Shamim MM, Abbasian J, Ghaffarieh A, Elhusseiny AM.
Ocular Surface Disease in Glaucoma Patients. Curr Eye Res 2023;48(3):219-230.
AbstractPURPOSE: To review the most recent studies in the literature regarding the ocular surface in glaucoma patients and treatment options aimed to reduce ocular surface disease in this population. METHODS: We performed a literature search in the electronic databases of PubMed CENT RAL, Google Scholar, EMBASE the Register of Controlled Trials, and Ovid MEDLINE using the following terms: "ocular surface", "dry eye", "glaucoma", "selective laser trabeculoplasty", "glaucoma surgery", "preservatives", "preservative free", "ocular surface disease index", "tear break up time", "MMP-9" and "conjunctival hyperemia". RESULTS: Over the last several years, several studies have demonstrated the changes to the ocular surface in the setting of glaucoma, the best tests for markers of dry eye, and how management can be altered to help address ocular surface disease routinely or in preparation for glaucoma surgery. CONCLUSION: Ocular surface disease in the glaucoma patient population is widely recognized. It should be addressed to maximize patient compliance and quality of life.
Sekimitsu S, Xiang D, Smith SL, Curran K, Elze T, Friedman DS, Foster PJ, Luo Y, Pasquale LR, Peto T, Segrè AV, Shweikh Y, Warwick A, Zhao Y, Wiggs JL, Zebardast N, and Consortium UKBEV.
Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden. JAMA Ophthalmol 2023;141(9):891-899.
AbstractIMPORTANCE: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. OBJECTIVE: To evaluate phenotypic features across genetic burden for POAG. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. MAIN OUTCOMES AND MEASURES: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. RESULTS: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). CONCLUSION AND RELEVANCE: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.
Sekimitsu S, Wang J, Elze T, Segrè AV, Wiggs JL, Zebardast N.
Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank. PLoS One 2022;17(6):e0270530.
AbstractBACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.
Sekimitsu S, Elze T, Zebardast N.
Impact of the Affordable Care Act on Glaucoma Severity at First Presentation. Ophthalmic Epidemiol 2023;30(3):326-329.
AbstractPURPOSE: To test whether the increase in insurance coverage in Massachusetts due to the Affordable Care Act (ACA) is associated with a decrease in glaucoma severity in patients presenting for the first time at a tertiary health system. METHODS: Clinical and billing data of first-time glaucoma patients from a tertiary health system in Massachusetts from 2006 to 2021 was used. Pre-ACA is defined as before 2014 and post-ACA is defined as after 2014. Visual field mean deviation was used to define glaucoma severity: greater than -6 dB, less than -6 dB and greater than -12 dB, and less than -12 dB was classified as "mild," "moderate," and "severe" respectively. Ordinal logistic regression models adjusted for age, race, gender, and insurance type were used to determine the odds of presenting with more severe glaucoma. RESULTS: 2,394 pre-ACA and 3,651 post-ACA first-time glaucoma patients were identified. There was no significant difference in the likelihood of more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.96; 95% CI 0.86-1.08; p=0.49) among the entire population. In stratified analyses, patients who utilized Medicaid for insurance had 52% decreased odds for presenting with more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.48; 95% CI 0.33-0.69; p<0.001). This remained significant after adjustment for age, race, and gender (adjusted OR=0.44; 95% CI 0.29-0.65; p<0.001). CONCLUSION: At a Massachusetts-based tertiary healthcare center, individuals on Medicaid were more likely to have more severe glaucoma at first presentation before the implementation of the ACA, compared to after.
Selvan H, Gupta S, Wiggs JL, Gupta V.
Juvenile-onset open-angle glaucoma - A clinical and genetic update. Surv Ophthalmol 2022;67(4):1099-1117.
AbstractJuvenile-onset open-angle glaucoma (JOAG) is a subset of primary open-angle glaucoma that is diagnosed before 40 years of age. The disease may be familial or non-familial, with proportions varying among different populations. Myocilin mutations are the most commonly associated. JOAG is characterized by high intraocular pressures (IOP), with many patients needing surgery. The mean age at diagnosis is in the 3rd decade, with a male preponderance. Myopia is a common association. The pathophysiology underlying the disease is immaturity of the conventional outflow pathways, which may or may not be observed on gonioscopy and anterior segment optical coherence tomography. The unique optic nerve head features include large discs with deep, steep cupping associated with high IOP-induced damage. Progression rates among JOAG patients are comparable to adult primary glaucomas, but as the disease affects younger patients, the projected disability from this disease is higher. Early diagnosis, prompt management, and life-long monitoring play an important role in preventing disease progression. Gene-based therapies currently under investigation offer future hope.
Seresirikachorn K, Thiamthat W, Annopawong K, Wanichwecharungruang B, Friedman DS, Vu DM.
Treatment Outcomes for Juvenile Open Angle Glaucoma in Thailand. J Glaucoma 2023;32(11):976-982.
AbstractPRCIS: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years. PURPOSE: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand. PATIENTS AND METHODS: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand. RESULTS: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0±10.1 years (range: 5-40 y), with male predominance (60.5%). Over 90% of patients had bilateral JOAG and 25% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10 µm adjusted odds ratio=1.29, P =0.01). Over 70% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5%) with a cumulative probability of complete success of 71.0%, 57.8%, 39.2%, and 26.9% and qualified success of 86.3%, 73.6%, 64.8%, and 45.7% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 ± 69.8 months (range: 13-153 mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure. CONCLUSIONS: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications.
Seresirikachorn K, Thiamthat W, Aramtiantamrong N, Traichaiyaporn S, Wanichwecharungruang B, Patel NA, Vu DM.
Two types of childhood glaucoma secondary to familial exudative vitreoretinopathy. J AAPOS 2023;
AbstractBACKGROUND: Glaucoma secondary to familial exudative vitreoretinopathy presents as angle closure by either neovascular or non-neovascular mechanisms. We analyze the presentation and outcomes of two types of childhood glaucoma secondary to familial exudative vitreoretinopathy (FEVR). METHODS: This retrospective cross-sectional study included all patients <18 years of age diagnosed with glaucoma after or concurrently with a diagnosis of FEVR between 2010 and 2020 from Queen Sirikit National Institute of Child Health in Bangkok, Thailand. Two groups were analyzed: neovascular or non-neovascular angle-closure status. Primary outcome measures were final visual acuity and intraocular pressure (IOP) in both groups. RESULTS: Of 144 FEVR patients, 8 children (5.5%; 11 eyes, 3 bilateral cases) developed childhood glaucoma. Mean time between FEVR presentation and glaucoma was 42.2 ± 40.0 months. In the neovascular group, 3 of 9 eyes presented with glaucoma at FEVR diagnosis; 3 of 9 eyes (33%) required glaucoma surgery. In the non-neovascular group, 2 eyes presented with acute angle closure secondary to a phacomorphic lens. Both were treated with trabeculectomy, with resolution of pupillary block. All eyes had stage 4B FEVR or greater. Six of 8 eyes had stable or better visual acuity, and 10 eyes (91%) had IOP <21 mm Hg at final follow-up. CONCLUSIONS: Childhood glaucoma secondary to FEVR is a rare complication caused by later stages of the disease. It may present as neovascular or non-neovascular angle closure, often requiring complex care. Therefore, awareness and adequate management of FEVR can help prevent additional morbidity from childhood glaucoma.
Seto B, Singh MK, Lemire CA, Arroyo JG.
Anterior versus posterior endoscopic cyclophotocoagulation: comparison of indications, populations, and outcomes. Int Ophthalmol 2021;41(9):3021-3028.
AbstractPURPOSE: To examine how indications, patient characteristics, and outcomes differ between anterior and posterior approaches of endoscopic cyclophotocoagulation (ECP) in the treatment of glaucoma. METHODS: This is a retrospective chart review of 9 anterior and 20 posterior ECP cases (n = 29). RESULTS: Posterior ECP cases were typically associated with a dramatic increase in intraocular pressure (IOP), whereas the anterior ECP was associated with chronically elevated pressures. The initial IOPs in mm Hg of posterior ECP cases (26.8 non-NVG; 35.2 NVG) were much greater than anterior ECP cases (17.8), and a greater overall reduction in IOP was observed in the posterior versus anterior ECP cases (10.3 posterior non-NVG; 21.3 posterior NVG; 3.6 anterior, P < .001). With procedural success defined as 6-month post-operative IOP falling within normal ranges and a decrease in either IOP or number of prescribed glaucoma medications, the success rate of ECP was 92% for posterior NVG, 89% for anterior and 75% for posterior non-NVG cases (P = .34), similar to the previous literature. Of the four unsuccessful cases, two resulted in a normal IOP but lacked a drop in pressure or reduction in medication burden, one resulted in a 6-point drop in IOP but remained at 23 mm Hg, and one resulted in phthisis bulbi (3%) from an initial pressure above 40 mm Hg. CONCLUSION: Endoscopic cyclophotocoagulation is an effective and safe procedure for severe glaucoma cases from both an anterior and posterior approach. Ophthalmologists should consider this procedure as part of their glaucoma treatment arsenal.
Shakarchi AF, Mihailovic A, West SK, Friedman DS, Ramulu PY.
Vision Parameters Most Important to Functionality in Glaucoma. Invest Ophthalmol Vis Sci 2019;60(14):4556-4563.
AbstractPurpose: To determine the importance of various vision parameters to functionality in glaucoma. Methods: Vision was measured using seven parameters: visual acuity (VA), contrast sensitivity (CS), integrated visual field (IVF), area under the log CS function (AULCSF), color vision, stereoacuity, and VA with noise (ViN). Likelihood ratio testing (LRT) determined if the full set of visual parameters significantly explained variability in 10 functional outcomes. For outcomes where the visual contribution was significant, dominance analysis determined the relative importance of the various visual parameters. Results: The analysis included 151 glaucoma patients. Mean age was 70 ± 6.8 years, and 47% were men. Significant visual contributions (LRT P < 0.05) were noted for glaucoma quality of life (GQL-15), reading speed, driving cessation, daily steps, and base of support while walking, but not for fear of falling, balance, gait velocity, stride velocity, and stride length while walking (LRT P > 0.05). The most important parameter (and percent contribution) to vision-explained variability were AULCSF for daily steps (45%), IVF for base of support (35%), VA for reading speed (34%), CS for GQL-15 (30%), and VA for driving cessation (26%). Conclusions: Measures of visual ability are important for several aspects of quality of life and functionality. The most important vision parameter for functionality differs depending on the domain studied. Reading and driving were explained by VA and IVF sensitivity. On the other hand, GQL-15 and daily steps were more heavily influenced by CS and AULCSF, which are rarely performed clinically.
Shazly TA, Latina MA.
Use of processed pericardium graft to plug patulous old sclerostomy track during glaucoma shunt revision for exposure. Ophthalmic Surg Lasers Imaging 2012;43(1):72-5.
AbstractThe authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges.
Shazly TA, Latina MA, Dagianis JJ, Chitturi S.
Effect of central corneal thickness on the long-term outcome of selective laser trabeculoplasty as primary treatment for ocular hypertension and primary open-angle glaucoma. Cornea 2012;31(8):883-6.
AbstractPURPOSE: To determine if central corneal thickness (CCT) impacts the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). METHODS: A retrospective chart review of consecutive patients, who underwent SLT as primary treatment for OHT and POAG, between 2002 and 2005, was performed. Partial correlation analysis was performed to correlate the CCT to the percentage of IOP reduction at 3 to 30 months after SLT. Independent samples t test was performed to compare mean percentage of IOP reduction in eyes with CCT less than 555 μm versus CCT 555 μm or greater. RESULTS: Eighty eyes of 47 patients were identified. The partial correlation coefficient value between the CCT and percentage of IOP reduction after SLT at 3 months was -0.253 (P = 0.025), at 12 months it was -0.22 (P = 0.049), and at 30 months it was 0.301 (P = 0.007). Independent samples t test showed that the mean percentage of IOP reduction in eyes with thinner corneas (CCT < 555 μm) was greater than that in thicker corneas (CCT ≥ 555 μm) at 3-, 6-, 9-, 12-, and 30-month post-SLT (P < 0.05). CONCLUSIONS: In patients with POAG and OHT, percentage of IOP reduction after SLT was significantly greater in eyes with thinner corneas (CCT < 555 μm). These findings indicate that patients treated with SLT as primary therapy who had thinner corneas demonstrated better IOP control for at least 30 months after SLT.
Shen LQ, Kloek CE, Turalba AV.
Assessing the Effect of a Glaucoma Surgical Curriculum in Resident Physicians. JAMA Ophthalmol 2015;133(9):1077-80.
AbstractIMPORTANCE: Subspecialty surgical training is an important part of resident education. We changed the glaucoma rotation in which postgraduate year 4 residents worked with multiple attending physicians with varying teaching styles to a structured surgical curriculum led by 2 dedicated preceptors, and we evaluated the effect on residents' surgical performance prospectively. OBSERVATIONS: A curriculum consisting of preoperative training, intraoperative teaching, postoperative feedback, and repetition was implemented for postgraduate year 4 residents between July 2, 2012, and June 30, 2014. In a class of 8 residents per year, the mean (SD) glaucoma surgical volume increased from 8.9 (0.8) cases in the prior year to 13.6 (2.5) in 2013 (mean difference, 4.8 cases; 95% CI, 2.4-7.1; P = .001) and 14.8 (4.2) in 2014 (mean difference, 5.9 cases; 95% CI, 2.1-9.6; P = .007). A self-assessment survey showed improvement in suturing (scores for each section range from 1 [worst] to 5 [best]; mean rating, 3.9 in the prior year vs 4.4 in 2013 [P = .04] and 4.5 in 2014 [P = .02]). A validated survey assessing overall surgical competency revealed improvement in handling adverse events (mean rating, 4.1 in the prior year vs 5.0 for both 2013 and 2014; both P < .001). CONCLUSIONS AND RELEVANCE: Despite the small sample size and nonrandomized study design, these data suggest that a structured surgical curriculum has advantages in teaching subspecialty surgery and might be considered by other ophthalmology training programs.
Shi M, Sun JA, Lokhande A, Tian Y, Luo Y, Elze T, Shen LQ, Wang M.
Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma. Transl Vis Sci Technol 2023;12(11):12.
AbstractPURPOSE: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. METHODS: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over ≥4 years. The artifacts are defined as RNFLT less than the known floor value of 50 µm. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of <2% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of >5% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. RESULTS: The mean absolute error and Pearson correlation of the artifact correction were 9.89 µm and 0.90 (P < 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of >10% and AR of >20% up to 0.03 and 0.04 (P < 0.001), respectively. Artifact correction improved (P < 0.05) the AUC for progression prediction in RNFLT maps with AR of ≤10%, >10%, and >20%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. CONCLUSIONS: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. TRANSLATIONAL RELEVANCE: Our model improves clinical usability of RNFLT maps with artifacts.
Shi Y, Wang H, Yin J, Li M, Zhang X, Xin C, Chen X, Wang N.
Microcatheter-assisted trabeculotomy versus rigid probe trabeculotomy in childhood glaucoma. Br J Ophthalmol 2016;100(9):1257-62.
AbstractPURPOSE: To compare microcatheter-assisted trabeculotomy with standard rigid probe trabeculotomy for the treatment of childhood glaucoma. METHODS: The early postoperative (12 months) results of microcatheter-assisted trabeculotomy (group 1) performed by single surgeon were retrospectively compared with those of rigid probe trabeculotomy (group 2) performed by the same surgeon in patients treated for childhood glaucoma. Success was defined as an intraocular pressure (IOP) <21 mm Hg with at least a 30% reduction from preoperative IOP with (qualified success) or without (complete success) the use of anti-glaucoma medication. RESULTS: A total of 43 eyes of 36 patients were included. Mean IOP in group 1 was significantly lower than that in group 2 at 6 months (17.0±5.1 vs 22.5±9.8; p=0.042), 9 months (16.3±5.0 vs 21.6±9.6; p=0.009) and 12 months (14.8±2.5 vs 19.0±7.1; p=0.049) postoperatively. The mean percentage reduction in IOP from preoperative to the last postoperative follow-up was greater in group 1 (47.3±17.7%) than in group 2 (34.2±21.9%) (p=0.036). group 1 demonstrated an 81.0% complete and 86.4% qualified success rate, exceeding the 51.6% complete (p=0.060) and 61.9% qualified (p=0.037) success rate of group 2. There were no long-term complications in either group, but choroidal detachment occurred in one eye in group 2. CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is a more effective treatment and is as safe as traditional trabeculotomy with a rigid probe for primary congenital glaucoma in the early postoperative course. TRIAL REGISTRATION NUMBER: ChiCTR-OCC-15005789, Results.
Shi Y, Wang H, Yin J, Zhang X, Li M, Xin C, Chen X, Wang N.
Outcomes of microcatheter-assisted trabeculotomy following failed angle surgeries in primary congenital glaucoma. Eye (Lond) 2017;31(1):132-139.
AbstractPurposeTo report surgical outcomes of microcatheter-assisted trabeculotomy following failed angle surgeries, and compare those with no previous angle surgery, in primary congenital glaucoma (PCG).MethodsThe early postoperative (12 months) results of 42 eyes of 36 patients who underwent microcatheter-assisted trabeculotomy by single surgeon for PCG were retrospectively analyzed. Group 1, 20 eyes of 16 patients, had no previous angle surgery. Group 2, 22 eyes of 20 patients, had one or two previous failed angle surgeries. Success was defined as an intraocular pressure (IOP) <21 mm Hg with at least a 30% reduction from preoperative IOP with (qualified success) or without (complete success) the use of antiglaucoma medication.ResultsMean IOP decreased from 31.5±7.2 mm Hg on 3 (median, range: 1-5) medications in Group 1 and 34.6±7.3 mm Hg on 3 (median, range: 1-4) medications in Group 2 preoperatively to 15.6±3.1 mm Hg on 0 (median, range: 0-4) medications in Group 1 and 16.0±4.6 mm Hg on 0 (median, range: 0-2) medications in Group 2 postoperatively at 12 months (both P<0.001), respectively. The mean percentage of IOP reduction from preoperative to last postoperative visit was 46.0±20.1% in Group 1 and 45.5±25.0% in Group 2, P=0.947. Qualified and complete successes were comparable between Group 1 and Group 2 (qualified success: 90.0% vs 77.3%, P=0.294; complete success: 78.9% vs 77.3%, P=0.853). Complications were minimal.ConclusionsMicrocatheter-assisted trabeculotomy achieved significant pressure-lowering effects with a reduction in medication use in PCG, and it represents a reasonable choice of initial and repeat surgical treatment for PCG.
Shieh E, Lee R, Que C, Srinivasan V, Guo R, DeLuna R, Pandit S, Simavli H, Seevaratnam R, Tsikata E, de Boer J, Chen TC.
Diagnostic Performance of a Novel Three-Dimensional Neuroretinal Rim Parameter for Glaucoma Using High-Density Volume Scans. Am J Ophthalmol 2016;169:168-78.
AbstractPURPOSE: To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. DESIGN: Reliability analysis. METHODS: setting: Institutional. STUDY POPULATION: Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES: One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. RESULTS: The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior-temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior-nasal sectors (P = .023-.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. CONCLUSIONS: Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region.
Shiga Y, Akiyama M, Nishiguchi KM, Sato K, Shimozawa N, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Yamaji T, Iwasaki M, Tsugane S, Oze I, Mikami H, Naito M, Wakai K, Yoshikawa M, Miyake M, Yamashiro K, Kashiwagi K, Iwata T, Mabuchi F, Takamoto M, Ozaki M, Kawase K, Aihara M, Araie M, Yamamoto T, Kiuchi Y, Nakamura M, Ikeda Y, Sonoda K-H, Ishibashi T, Nitta K, Iwase A, Shirato S, Oka Y, Satoh M, Sasaki M, Fuse N, Suzuki Y, Cheng C-Y, Khor CC, Baskaran M, Perera S, Aung T, Vithana EN, Cooke Bailey JN, Kang JH, Pasquale LR, Haines JL, Wiggs JL, Burdon KP, Gharahkhani P, Hewitt AW, Mackey DA, Macgregor S, Craig JE, Allingham RR, Hauser M, Ashaye A, Budenz DL, Akafo S, Williams SEI, Kamatani Y, Nakazawa T, Kubo M.
Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. Hum Mol Genet 2018;27(8):1486-1496.
AbstractPrimary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.
Shoji MK, Cousins CC, Saini C, Silva RNE, Wang M, Brauner SC, Greenstein SH, Pasquale LR, Shen LQ.
Paired Optic Nerve Microvasculature and Nailfold Capillary Measurements in Primary Open-Angle Glaucoma. Transl Vis Sci Technol 2021;10(7):13.
AbstractPurpose: To assess microvascular beds in the optic nerve head (ONH), peripapillary tissue, and the nailfold in patients with primary open-angle glaucoma (POAG) versus controls. Methods: Patients with POAG (n = 22) and controls (n = 12) underwent swept-source optical coherence tomography angiography of ophthalmic microvasculature and nailfold video capillaroscopy of the hand. The main outcomes were vessel density (VD) and blood flow of the ONH, the peripapillary and the nailfold microvasculatures. Results: Patients with POAG were younger than controls (63.5 ± 9.4 vs. 69.9 ± 6.5 years, P = 0.03). Deep ONH VD and blood flow were lower in patients with POAG than controls (39.1% ± 3.5% vs. 43.8% ± 5.7%; 37.8% ± 5.3% vs. 46.0% ± 7.8%, respectively, P < 0.02 for both); similar results were observed with peripapillary VD (37.9 ± 2.6%, 43.4 ± 7.6%, respectively, P = 0.03). Nailfold capillary density and blood flow were lower in patients with POAG than controls (8.8 ± 1.0 vs. 9.8 ± 0.9 capillaries/mm; 19.9 ± 9.4 vs. 33.7 ± 9.8 pL/s, respectively; P < 0.009 for both). After adjusting for age and gender, deep ONH VD and blood flow, peripapillary VD, and nailfold capillary blood flow were lower in POAG than controls (β = -0.04, -0.07, -0.05, -13.19, respectively, P ≤ 0.046 for all). Among all participants, there were positive correlations between deep ONH and nailfold capillary blood flow (Pearson's correlation coefficient r = 0.42, P = 0.02), peripapillary and nailfold capillary density (r = 0.43, P = 0.03), and peripapillary and nailfold capillary blood flow (r = 0.49, P = 0.01). Conclusions: Patients with POAG demonstrated morphologic and hemodynamic alterations in both ophthalmic and nailfold microvascular beds compared to controls. Translational Relevance: The concomitant abnormalities in nailfold capillaries and relevant ocular vascular beds in POAG suggest that the microvasculature may be a target for POAG treatment.
Shroff S, Gu SZ, Vardhan S A, Mani I, Aziz K, P N, Datta D, Friedman DS.
Screening first-degree relatives of glaucoma patients reveals barriers to participation. Br J Ophthalmol 2021;
AbstractPURPOSE: To report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India. METHODS: 1598 glaucoma patients were contacted via letter or letter and phone call and asked to bring their siblings and children to a glaucoma screening. Participants underwent standardised eye examinations and completed questionnaires that assessed barriers to participation and awareness of glaucoma risk. Two-proportion z-tests were used to compare categorical data. Costs associated with the screening were recorded. RESULTS: 206 probands (12.9%) attended the screening along with 50 siblings and children. Probands were nearly twice as likely to attend if they had been contacted via both letter and phone call rather than letter only. Over half of probands reported that their relatives could not participate because they did not live in the region, and one-fifth reported that their relatives had other commitments. Fifty-eight per cent of the siblings and children who attended did not know that they were at increased risk for glaucoma due to their family history, and 32.0% did not know that the relative who had invited them to the screening had glaucoma. Thirteen siblings and children (26.0% of those who attended) were found to have findings concerning for glaucoma. The average cost per first-degree relative who was screened was INR2422 (£26). CONCLUSION: Participation in this glaucoma screening campaign was poor. The major barrier to participation was distance from the screening site and associated indirect costs. Better strategies for bringing first-degree relatives in for examinations are needed.
