Glaucoma

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Pasquale LR, Borrás T, Fingert JH, Wiggs JL, Ritch R. Exfoliation syndrome: assembling the puzzle pieces. Acta Ophthalmol 2016;94(6):e505-12.Abstract

PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. CONCLUSION: Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS.

Pasquale LR, Loomis SJ, Kang JH, Yaspan BL, Abdrabou W, Budenz DL, Chen TC, Delbono E, Friedman DS, Gaasterland D, Gaasterland T, Grosskreutz CL, Lee RK, Lichter PR, Liu Y, McCarty CA, Moroi SE, Olson LM, Realini T, Rhee DJ, Schuman JS, Singh K, Vollrath D, Wollstein G, Zack DJ, Allingham RR, Pericak-Vance MA, Weinreb RN, Zhang K, Hauser MA, Richards JE, Haines JL, Wiggs JL. CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States. Am J Ophthalmol 2013;155(2):342-353.e5.Abstract
PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective observational case series. METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results. RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05). CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.
Pasquale LR, Brusie S. The blue arc entoptic phenomenon in glaucoma (an American ophthalmological thesis). Trans Am Ophthalmol Soc 2013;111:46-55.Abstract
PURPOSE: To determine whether the blue arc entoptic phenomenon, a positive visual response originating from the retina with a shape that conforms to the topology of the nerve fiber layer, is depressed in glaucoma. METHODS: We recruited a cross-sectional, nonconsecutive sample of 202 patients from a single institution in a prospective manner. Subjects underwent full ophthalmic examination, including standard automated perimetry (Humphrey Visual Field 24-2) or frequency doubling technology (Screening C 20-5) perimetry. Eligible patients viewed computer-generated stimuli under conditions chosen to optimize perception of the blue arcs. Unmasked testers instructed patients to report whether they were able to perceive blue arcs but did not reveal what response was expected. We created multivariable logistic regression models to ascertain the demographic and clinical parameters associated with perceiving the blue arcs. RESULTS: In multivariable analyses, each 0.1 unit increase in cup-disc ratio was associated with 36% reduced likelihood of perceiving the blue arcs (odds ratio [OR] = 0.66 [95% confidence interval (CI): 0.53-0.83], P<.001). A smaller mean defect was associated with an increased likelihood of perceiving the blue arcs (OR=1.79 [95% CI: 1.40-2.28]); P<.001), while larger pattern standard deviation (OR=0.72 [95% CI: 0.57-0.91]; P=.005) and abnormal glaucoma hemifield test (OR=0.25 [0.10-0.65]; P=.006) were associated with a reduced likelihood of perceiving them. Older age and media opacity were also associated with an inability to perceive the blue arcs. CONCLUSION: In this study, the inability to perceive the blue arcs correlated with structural and functional features associated with glaucoma, although older age and media opacity were also predictors of this entoptic response.
Pasquale LR, Hyman L, Wiggs JL, Rosner BA, Joshipura K, McEvoy M, McPherson ZE, Danias J, Kang JH. Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study. Ophthalmology 2016;123(11):2318-2327.Abstract

PURPOSE: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes. DESIGN: Prospective cohort study. PARTICIPANTS: Health Professionals Follow-up Study participants (40 536 men) followed biennially from 1986 to 2012. At each 2-year risk period, eligible participants were aged 40+ years, were free of POAG, and reported eye examinations. METHODS: By using validated questions, we updated participants' status on number of natural teeth, teeth lost, periodontal disease with bone loss, and root canal treatments. MAIN OUTCOME MEASURES: During follow-up, 485 incident cases of POAG were confirmed with medical records and classified into subtypes defined by intraocular pressure (IOP; ≥ or <22 mmHg) or visual field (VF) loss pattern at diagnosis (peripheral loss only or early paracentral loss). Multivariable relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Number of natural teeth, periodontal disease, and root canal treatment were not associated with POAG. However, compared with no report of tooth loss, a report of losing teeth within the past 2 years was associated with a 1.45-fold increased risk of POAG (95% CI, 1.06-1.97); in particular, a report within the past 2 years of both losing teeth and having a prevalent diagnosis of periodontal disease was associated with a 1.85-fold increased risk of POAG (95% CI, 1.07-3.18). The associations with recent tooth loss were not significantly different for the POAG subtypes (P for heterogeneity ≥0.36), although associations were strongest in relation to the POAG subtypes with IOP <22 mmHg (MVRR, 1.93; 95% CI, 1.09-3.43) and early paracentral VF loss (MVRR, 2.27; 95% CI, 1.32-3.88). CONCLUSIONS: Although the number of natural teeth was not associated with risk of POAG, recent tooth loss was associated with an increased risk of POAG. Because these findings may be due to chance, they need confirmation in larger studies.

Poon LY-C, Chodosh J, Vavvas DG, Dohlman CH, Chen TC. Endoscopic Cyclophotocoagulation for the Treatment of Glaucoma in Boston Keratoprosthesis Type II Patient. J Glaucoma 2017;26(4):e146-e149.Abstract

We describe the surgical technique of endoscopic cyclophotocoagulation in a Boston keratoprosthesis type II patient. This patient with ocular cicatricial pemphigoid had pars plana endoscopic cyclophotocoagula through wounds created in the eyelids.

Porporato N, Baskaran M, Perera S, Tun TA, Sultana R, Tan M, Quah JHM, Allen JC, Friedman D, Cheng CY, Aung T. Evaluation of meridional scans for angle closure assessment with anterior segment swept-source optical coherence tomography. Br J Ophthalmol 2021;105(1):131-134.Abstract
BACKGROUND/AIMS: As swept-source optical coherence tomography (SS-OCT) simultaneously obtains 128 meridional scans, it is important to identify which scans are playing the main role in classifying gonioscopic angle closure to simplify the analysis. We aimed to evaluate the diagnostic performance of every meridional scan in its ability to detect gonioscopic angle closure. METHODS: Observational study with 2027 phakic subjects consecutively recruited from a community polyclinic. Gonioscopy and SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle, while SS-OCT was defined as iridotrabecular contact anterior to the scleral spur. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic performance of each single scan, the sequential anticlockwise cumulative effect of those single scans and different combinations of them. RESULTS: The AUCs of each scan ranged from 0.73 to 0.82. The single scan at 80°-260° had the highest AUC (0.82, 95% CI 0.79 to 0.84) and performed significantly better than most of the temporonasal scans (from 0° to 52° and from 153° to 179°). The superoinferior scans achieved higher AUCs compared with the temporonasal ones. When assessing the cumulative effect of adding individual scans consecutively, the peak AUC (0.80) was obtained when considering the superoinferior scans closer to 80°-85°, but no further positive cumulative effect was seen when adding the rest of the temporonasal scans of the circumference. CONCLUSIONS: In conclusion, the single SS-OCT scan at 80°-260° had the highest diagnostic performance. Our study suggests that the 360° evaluation may not translate to better clinical utility for detection of gonioscopic angle closure.
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Qian CX, Hassanaly S, Harissi-Dagher M. Anterior Segment Optical Coherence Tomography in the Long-Term Follow-up andDetection of Glaucoma in Boston TypeIKeratoprosthesis. Ophthalmology 2015;122(2):317-25.Abstract

PURPOSE: To evaluate the role of anterior segment (AS) optical coherence tomography (OCT) as a standardized method of imaging Boston type I keratoprosthesis (KPro) after surgery, particularly in the visualization of iris and angle structures. DESIGN: Prospective case series. PARTICIPANTS: Twenty patients who underwent KPro implantation in 1 eye. METHODS: Patients underwent AS OCT imaging before surgery. After KPro implantation, patients were imaged using the AS single, dual, and quad scans to obtain transverse images of the eye every 15° over 360°. High-resolution, corneal quad, and anterior chamber scans were also obtained. This imaging protocol allowed juxtaposition and comparison of the same imaging coordinates obtained before surgery and 3, 6, and 12 months after surgery. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), glaucoma progression on clinical examination and formal visual field testing, and anatomic angle changes on AS OCT defined by angle closure, peripheral anterior synechiae (PAS), iris-KPro backplate touch, and graft-host interface changes over time. RESULTS: Mean follow-up was 18.8±3.2 months. The average preoperative VA was 1.9±0.5 logarithm of the minimum angle of resolution. After surgery, VA improved to 1.0±0.9 at last follow-up (P = 0.002). Fourteen of 20 patients had glaucoma before surgery. After surgery, 5 of these patients deteriorated clinically and 1 de novo diagnosis of glaucoma was made. On OCT, the average total degrees of angle closure for all patients increased from 158.5±158.9° before surgery to 205.4±154.0° after surgery (P = 0.04). The number of eyes with 360° of PAS increased from 6 of 20 before surgery to 9 of 20 after surgery. Iris-backplate touch was demonstrated in 5 of 20 patients, with an average area of involvement of 24.2±36.2°. Overall, of the 12 of 20 patients with clear signs of anatomic angle narrowing and synechiae progression on imaging, 3 had glaucoma deterioration detected by clinical examination. In the other 9 patients, angle changes on OCT were not accompanied by any detectable clinical signs of glaucomatous deterioration. CONCLUSIONS: Anterior segment OCT can be used to observe anatomic changes after KPro implantation that cannot be detected otherwise. We were unable to demonstrate a correlation between anatomic features and clinical progression.

Qiu M, Woreta FA, Boland MV. Microinvasive Glaucoma Surgery in US Ophthalmology Residency: Surgical Case Log Cross-sectional Analysis and Proposal for New Glaucoma Procedure Classification. J Glaucoma 2021;30(7):621-628.Abstract
PRECIS: A cross-sectional sample of the US ophthalmology residency graduating class of 2018 revealed that 18.4% of residents logged <5 traditional glaucoma surgeries, and 63.4% logged at least 1 microinvasive glaucoma surgery (MIGS). PURPOSE: Describe the state of MIGS in US ophthalmology residency training and propose a glaucoma procedure classification system for residents' surgical case logs. METHODS: Deidentified case logs from residents graduating in 2018 were requested from US residency program directors. RESULTS: Case logs were received for 152/488 (31%) residents from 36/115 (31%) programs. The mean number of traditional glaucoma surgeries per resident was 9.0±5.9 (range: 0 to 31). The mean number of MIGS per resident was 5.2±8.9 cases (range: 0 to 58). There were 28/152 (18.4%) residents from 16/36 (44.4%) programs who logged <5 traditional glaucoma surgeries as primary surgeon, and 3/152 (2.0%) residents from 3/36 (8.3%) programs who logged zero traditional glaucoma surgeries as primary surgeon. There were 98/152 (64.5%) residents from 32/36 (88.8%) programs who logged <5 MIGS as primary surgeon, and 48/152 (31.6%) residents from 25 of 36 (69.4%) programs who logged zero MIGS as primary surgeon. There were 104/152 (63.4%) residents from 33/36 (91.6%) programs who logged at least 1 MIGS as primary surgeon; there were 3/36 (8.3%) residency programs where no resident logged any MIGS as primary surgeon. CONCLUSIONS: US ophthalmology residents' MIGS experience varies widely. Residents can satisfy glaucoma surgery requirements with some MIGS, even in the absence of adequate traditional glaucoma surgeries. We propose a residency case log classification system that better reflects the growing role of MIGS in clinical practice and helps ophthalmic educators more accurately track procedures requiring related skills.
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Radcliffe NM, Smith SD, Syed ZA, Park SC, Ehrlich JR, De Moraes CG, Liebmann JM, Ritch R. Retinal blood vessel positional shifts and glaucoma progression. Ophthalmology 2014;121(4):842-8.Abstract
PURPOSE: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with ≥8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (<-0.02 decibels [dB]/year), moderate (-0.02 to -0.65 dB/year), or fast (≥-0.65 dB/year) progression. To determine whether graders' assessments of RBV positional shifts were false-positives, a control group consisting of 33 patients with glaucoma with 2 sets of photographs taken on the same day was included. METHODS: Masked graders reviewed serial photographs aligned with automated alternation flicker (EyeIC, Narbeth, PA) and assessed them for the presence of any discrete RBV positional shifts (2 graders) and for traditional measures of structural progression (2 graders), including neuroretinal rim loss, parapapillary atrophy progression, and disc hemorrhage (DH). MAIN OUTCOME MEASURES: Presence or absence of RBV positional shifts, rates of VF progression, and presence or absence of traditional measures of structural progression. RESULTS: A total of 158 image sets (125 longitudinal and 33 same-day controls) from patients with glaucoma were included. Retinal blood vessel shifts were noted in 33 of 125 (26.4%) longitudinally followed glaucomatous eyes and 2 of 33 (6%) same-day control patients (P = 0.01). Agreement between graders I and II was 90.4% (kappa=0.77; P< 0.001). Eyes with RBV positional change progressed more rapidly than those without (-0.55 vs. -0.29 dB/year; 95% confidence interval [CI], 0.03-0.48); P = 0.03). Retinal blood vessel shift was present in 12.1% of minimal progressors versus 31.5% of moderate and fast progressors (P = 0.04). Rate of VF progression was statistically associated with RBV shift (odds ratio [OR], 2.2; 95% CI, 1.1-4.5; P = 0.03). Other variables significantly associated with RBV shift included neuroretinal rim loss (OR, 21.9; 95% CI, 5.7-83.6; P< 0.001) and DH (OR, 4.6; 95% CI, 1.5-15.5; P< 0.01). A multivariable model revealed that rim loss and DH, but not rate of functional change, were significantly associated with RBV shift. CONCLUSIONS: Retinal blood vessel positional shifts occurred in eyes with functionally progressive glaucoma, neuroretinal rim loss, and DH. This is a novel clinical finding that could help identify glaucoma progression or individuals at higher risk for future progression.
Radhakrishnan S, Chen PP, Junk AK, Nouri-Mahdavi K, Chen TC. Laser Peripheral Iridotomy in Primary Angle Closure: A Report by the American Academy of Ophthalmology. Ophthalmology 2018;125(7):1110-1120.Abstract
PURPOSE: To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). METHODS: Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. RESULTS: Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2% to 57% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0%-8% of PAC suspect (PACS), 42% to 67% of PAC, 21% to 47% of acute PAC (APAC), and 83%-100% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0% to 0.3% per year in PACS and 0% to 4% per year in PAC. Complications after LPI included IOP spike (8-17 mmHg increase from baseline in 6%-10%), dysphotopsia (2%-11%), anterior chamber bleeding (30%-41%), and cataract progression (23%-39%). CONCLUSIONS: Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.
Rahman SI, Turalba A. Anticoagulation in Glaucoma Surgery. Semin Ophthalmol 2017;:1-4.Abstract
Anticoagulation medications are used commonly, particularly in an elderly population. There are many systemic diseases and scenarios that require modulation of coagulation to prevent serious adverse outcomes. While there is some consensus about their use in cataract surgery, there is less certainty about their management with glaucoma surgery. Glaucoma surgery presents a unique challenge when considering anticoagulation. Currently, there is great diversity in surgeon practices regarding anticoagulation in glaucoma surgery. Based on available evidence, it is unclear whether it is beneficial to hold anticoagulation, with or without bridging therapy, leading up to a planned surgery. Considering the potential serious adverse outcomes related to holding anticoagulation therapy, altering these medications for glaucoma surgery should be done sparingly and in consultation with the primary prescriber of such medications.
Rao RC, Ballard TNS, Chen TC. Iris heterochromia and unilateral eyelash hypertrichosis. JAMA 2015;313(19):1967-8.
Ratanawongphaibul K, Tsikata E, Zemplenyi M, Lee H, Margeta MA, Ondeck CL, Kim J, Pan BX, Petrakos P, Coleman AL, Yu F, de Boer JF, Chen TC. Earlier Detection of Glaucoma Progression Using High-Density 3D Spectral-Domain Optical Coherence Tomography Optic Nerve Volume Scans. Ophthalmol Glaucoma 2021;Abstract
PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) neuroretinal rim measurements. DESIGN: Prospective longitudinal cohort study PARTICIPANTS: One hundred and twenty-four eyes of 124 open angle glaucoma patients METHODS: Over a 5-year period, 124 open angle glaucoma patients had yearly DP, VFs, SD-OCT RNFL thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Progression by DP and VF occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if there was change greater than test-retest variability. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa coefficients were used to measure agreement of progressing eyes among modalities. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 modalities RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared to DP (16.1%, P<0.001), and global RNFL thickness (15.3%, P<0.001) respectively. Global MDB thickness detected glaucoma progression earlier than either DP (23 versus 44 months; P<0.001) or global RNFL thickness (23 versus 33 months; P<0.001). Among MDB progressing eyes, 46.2% were simultaneously or later confirmed by other conventional modalities. Agreement of glaucoma progressing eyes for all 4 modalities in paired fashion were slight to fair (k=0.095-0.300). CONCLUSION: High-density 3D SD-OCT neuroretinal rim measurements detected glaucoma progression approximately 1-2 years earlier compared to current clinically available structural tests (i.e. disc photos and 2D RNFL thickness measurements).
Razeghinejad R, Lin MM, Lee D, Katz JL, Myers JS. Pathophysiology and management of glaucoma and ocular hypertension related to trauma. Surv Ophthalmol 2020;65(5):530-547.Abstract
Ocular trauma is a significant cause of blindness worldwide, particularly if associated with glaucoma. Direct damage from blunt or penetrating trauma, bleeding, inflammation, lens-related problems, orbital and brain vascular pathologies related to trauma, and chemical injuries may increase intraocular pressure and lead to traumatic glaucoma. Treatment may be as simple as eliminating the underlying cause in some conditions or management can be challenging, depending on the mechanism of damage. If proper management is not undertaken, visual outcomes can be poor. We discuss a broad spectrum of trauma-related mechanisms of intraocular pressure elevation, as well as their management.
da Ricardo JRS, Medhi J, Pineda R. Femtosecond laser-assisted keratopigmentation for the management of visual disabilities due to peripheral iridectomies. J Glaucoma 2015;24(4):e22-4.Abstract

PURPOSE: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. DESIGN: Case report. METHODS: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. RESULTS: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. CONCLUSIONS: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery.

Roh M, Zhang Y, Murakami Y, Thanos A, Lee SC, Vavvas DG, Benowitz LI, Miller JW. Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS One 2012;7(7):e40065.Abstract
BACKGROUND: Visual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC) axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP) are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor-α (TNF-α) as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF-α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death. METHODOLOGY/PRINCIPAL FINDINGS: Episcleral vein cauterization (EVC) caused intraocular pressure (IOP) to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH). Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs. CONCLUSIONS/SIGNIFICANCE: Ocular hypertension (OHT) triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF-α antagonists or suppressors of inflammation.
Rong SS, Lu SY, Matsushita K, Huang C, Leung CKS, Kawashima R, Usui S, Tam POS, Young AL, Tsujikawa M, Zhang M, Nishida K, Wiggs JL, Tham CC, Pang CP, Chen LJ. Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese. Exp Eye Res 2019;180:129-136.Abstract
The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P = 4.3 × 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P = 0.017, OR = 0.70, I = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P<0.005). Furthermore, two haplotypes, C-C (P = 1.13 × 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.
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Saboo US, Amparo F, Shikari H, Dana R. Prevalence of ocular hypertension and glaucoma in patients with chronic ocular graft-versus-host disease. Graefes Arch Clin Exp Ophthalmol 2016;254(5):923-8.Abstract

PURPOSE: To evaluate the prevalence of ocular hypertension (OHT) and glaucoma in patients with chronic ocular graft-versus-host disease (GVHD). METHODS: We performed a retrospective chart review of 218 patients diagnosed with chronic ocular GVHD. Ocular hypertension was defined as intraocular pressure (IOP) ≥ 24 mmHg in either eye without any glaucomatous optic disc changes. Glaucoma suspect was defined as optic disc changes with a cup-to-disc ratio ≥ 0.7 in either eye or asymmetry of ≥ 0.3 between the two eyes. Glaucoma was defined by glaucomatous optic disc changes plus glaucomatous visual field defects in two consecutive reliable visual field tests. The number of cases of ocular hypertension, glaucoma, and glaucoma suspects was evaluated. RESULTS: Thirty-three patients (15 %) were diagnosed with OHT, eight patients (3.6 %) with suspicion of glaucoma, and one patient (0.4 %) with glaucoma. OHT occurred within 6 months of developing ocular GVHD in 60 % of the cases and within the first year in 76 %. High IOP normalized in 67 % of patients when the dosage of topical or systemic corticosteroids was lowered, and 27 % of patients required anti-glaucoma therapy. CONCLUSIONS: Ocular hypertension is a common complication in patients with ocular GVHD, with a prevalence of 15 %. The rise in intraocular pressure is often transient and resolves with management of corticosteroids in most cases. However, clinicians should be aware that nearly one-third of the patients with OHT might require anti-glaucoma treatment. The prevalences of glaucoma and suspicion of glaucoma were not higher than in the general population.

Saeedi OJ, Elze T, D'Acunto L, Swamy R, Hegde V, Gupta S, Venjara A, Tsai J, Myers JS, Wellik SR, De Moraes CG, Pasquale L, Shen LQ, Boland MV. Reply. Ophthalmology 2019;126(10):e78-e79.
Seto B, Singh MK, Lemire CA, Arroyo JG. Anterior versus posterior endoscopic cyclophotocoagulation: comparison of indications, populations, and outcomes. Int Ophthalmol 2021;Abstract
PURPOSE: 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.

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