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Fulltext Glaucomatous neurodegeneration: an eye on tumor necrosis factor-alpha

Agarwal R, Agarwal P

Indian J Ophthalmol, 2012 Jul;60(4):255-61.
PMID: 22824592 DOI: 10.4103/0301-4738.98700

Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.

Matched MeSH terms: Glaucoma/complications*
Fulltext Trabeculectomy--a review and 2 year follow up

Jaais F

Med J Malaysia, 2004 Aug;59(3):378-83.
PMID: 15727384

This study reviewed the trabeculectomies (TEs) carried out in University Malaya Medical Center between 1994 to 1998. One hundred and nine of 132 eyes operated were in the primary glaucoma group of which 63 (47.7%) were of the open angle type and 46 (34.8%) were of the angle closure type. Twenty-three eyes belong to the secondary glaucoma group. Sixty-five eyes had plain or non-augmented trabeculectomy (TE) while 20 were augmented with mitomycin C (MMC) and 11 with 5 flourouracil (5FU). In 31 eyes the plain TEs were combined with extracapsular cataract extraction (ECCE) and 4 with phacoemusification. One case had combined ECCE and augmented trabeculectomy with mitomycin-C. The patients were followed up at 1 month, 6 months, 1 year and 2 years. Ninety-four of 132 (71.2%) eyes had successful surgery with intraocular pressure (IOP) of less than 21 mmHg (tonometric success) at the end of 2 years. Four of these patients needed topical medication for the IOP control. More failures were seen in patients with cystic blebs than those with diffuse blebs. Complications include hypotony, shallow anterior chamber, cataracts and hyphaema. The majority of cases (53%) had no complications.

Matched MeSH terms: Glaucoma/complications
Modified Bahasa Malaysia version of VF-14 questionnaire: assessing the impact of glaucoma in rural area of Malaysia

Maharajah KR, Tet CM, Yaacob A, Tajudin LS, Foster PJ

Clin Exp Ophthalmol, 2008 Apr;36(3):222-31.
PMID: 18412590 DOI: 10.1111/j.1442-9071.2008.01719.x

To evaluate the functional impairment of glaucoma patients, using a modified Bahasa Malaysia version of VF-14 questionnaire, and to correlate the score with the severity of the disease.

Matched MeSH terms: Glaucoma/complications*
Difference in glaucoma progression between the first and second eye after consecutive bilateral glaucoma surgery in patients with bilateral uveitic glaucoma

Din NM, Talat L, Isa H, Tomkins-Netzer O, Barton K, Lightman S

Graefes Arch Clin Exp Ophthalmol, 2016 Dec;254(12):2439-2448.
PMID: 27495303

PURPOSE: To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE).
METHODS: This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software.
RESULTS: The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF.
CONCLUSION: In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit.

Matched MeSH terms: Glaucoma/complications
Fulltext Leprotic iritis and blindness

Hobbs HE

Int. J. Lepr. Other Mycobact. Dis., 1972;40(4):366-74.
PMID: 4677492
Matched MeSH terms: Glaucoma/complications
Magnesium acetyltaurate protects against endothelin-1 induced RGC loss by reducing neuroinflammation in Sprague dawley rats

Nor Arfuzir NN, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM

Exp Eye Res, 2020 05;194:107996.
PMID: 32156652 DOI: 10.1016/j.exer.2020.107996

Endothelin-1 (ET-1), a potent vasoconstrictor, plays a significant role in the pathophysiology of ocular conditions like glaucoma. Glaucoma is characterized by apoptotic loss of retinal ganglion cells (RGCs) and loss of visual fields and is a leading cause of irreversible blindness. In glaucomatous eyes, retinal ischemia causes release of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and promotes activation of transcription factors such as nuclear factor kappa B (NFKB) and c-Jun. Magnesium acetyltaurate (MgAT) has previously been shown to protect against ET-1 induced retinal and optic nerve damage. Current study investigated the mechanisms underlying these effects of MgAT, which so far remain unknown. Sprague dawley rats were intravitreally injected with ET-1 with or without pretreatment with MgAT. Seven days post-injection, retinal expression of IL-1β, IL-6, TNF-α, NFKB and c-Jun protein and genes was determined using multiplex assay, Western blot and PCR. Animals were subjected to retrograde labeling of RGCs to determine the extent of RGC survival. RGC survival was also examined using Brn3A staining. Furthermore, visual functions of rats were determined using Morris water maze. It was observed that pre-treatment with MgAT protects against ET-1 induced increase in the retinal expression of IL-1β, IL-6 and TNF-α proteins and genes. It also protected against ET-1 induced activation of NFKB and c-Jun. These effects of MgAT were associated with greater RGC survival and preservation of visual functions in rats. In conclusion, MgAT prevents ET-1 induced RGC loss and loss of visual functions by suppressing neuroinflammatory reaction in rat retinas.

Matched MeSH terms: Glaucoma/complications
Ocular Surface Disease in Glaucoma: Effect of Polypharmacy and Preservatives

Ramli N, Supramaniam G, Samsudin A, Juana A, Zahari M, Choo MM

Optom Vis Sci, 2015 Sep;92(9):e222-6.
PMID: 25730335 DOI: 10.1097/OPX.0000000000000542

PURPOSE: To evaluate the prevalence of ocular surface disease (OSD) in glaucoma and nonglaucoma subjects using different clinical tests and to determine the effect of number of antiglaucoma medications and preservatives on OSD.
METHODS: This is a cross-sectional, case-comparison study at the Eye Clinic of the University of Malaya Medical Centre, Malaysia, between June 2012 and January 2013. Glaucoma subjects (n = 105) using topical antiglaucoma medications were compared with control subjects (n = 102) who were not on any topical medications. The presence of OSD was assessed using the tear film breakup time (TBUT) test, corneal staining, Schirmer test, and Ocular Surface Disease Index (OSDI) questionnaire grading.
RESULTS: The prevalence of OSD varied from 37 to 91% in the glaucoma group, depending on the type of clinical test. More subjects in the glaucoma group had corneal staining (63% vs. 36%, p = 0.004), abnormal Schirmer tests (39% vs. 25%, p = 0.049), and moderate OSDI symptoms (17% vs. 7%, p = 0.028). The percentage with abnormal TBUT increased with higher numbers of topical medications and was high with both benzalkonium chloride-containing and preservative-free eye drops (90% and 94%, respectively, both p < 0.001). Benzalkonium chloride was associated with a nearly three times higher odds ratio of showing abnormal OSDI.
CONCLUSIONS: Ocular surface disease is common in those using topical antiglaucoma medications. Abnormal TBUT is associated with increasing number of eye drops and benzalkonium chloride-containing eye drops, although this also occurs with the use of preservative-free eye drops.
Study site: Eye Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia,

Matched MeSH terms: Glaucoma/complications*
The Association Between Visual Field Reliability Indices and Cognitive Impairment in Glaucoma Patients

Raman P, Khy Ching Y, Sivagurunathan PD, Ramli N, Mohd Khalid KH

J Glaucoma, 2019 08;28(8):685-690.
PMID: 31033782 DOI: 10.1097/IJG.0000000000001269

PRECIS: This prospective cross-sectional study found that patients with cognitive impairment (CI) are more likely to produce unreliable visual field (VF) tests, especially with higher false-negative (FN) responses and consequent overestimation of mean deviation (MD).
AIM: Aging-associated CI can impair the ability of individuals to perform a VF test and compromise the reliability of the results. We evaluated the association between neurocognitive impairment and VF reliability indices in glaucoma patients.
METHODS: This prospective, cross-sectional study was conducted in the Ophthalmology Department, Hospital Kuala Pilah, Malaysia, and included 113 eyes of 60 glaucoma patients with no prior diagnosis of dementia. Patients were monitored with the Humphrey Visual Field Analyzer using a 30-2 SITA, standard protocol, and CI was assessed using the clock drawing test (CDT). The relationships between the CDT score, MD, pattern standard deviation, Visual Field Index (VFI), fixation loss (FL), false-positive values, and FN values were analyzed using the ordinal regression model.
RESULTS: Glaucoma patients older than 65 years had a higher prevalence of CI. There was a statistically significant correlation between CDT scores and glaucoma severity, FL, FN, and VFI values (rs=-0.20, P=0.03; rs=-0.20, P=0.04; rs=-0.28, P=0.003; rs=0.21, P=0.03, respectively). In a multivariate model adjusted for age and glaucoma severity, patients with lower FN were significantly less likely to have CI (odds ratio, 0.91; 95% confidence interval, 0.89-0.93) and patients with higher MD were more likely to have CI (odds ratio, 1.10; 95% confidence interval, 1.05-1.16); false positive, FL, pattern standard deviation, and VFI showed no significant correlation.
CONCLUSION: Cognitive decline is associated with reduced VF reliability, especially with higher FN rate and overestimated MD. Screening and monitoring of CI may be important in the assessment of VF progression in glaucoma patients.

Matched MeSH terms: Glaucoma/complications*