Untargeted metabolomics in the aqueous humor reveals the involvement of TAAR pathway in glaucoma.

Understanding the metabolic dysfunctions and underlying complex pathological mechanisms of neurodegeneration in glaucoma could help discover disease pathways, identify novel biomarkers, and rationalize newer therapeutics. Therefore, we aimed to investigate the local metabolomic alterations in the aqueous humor and plasma of primary glaucomatous patients. This study cohort comprised primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and cataract control groups. Aqueous humor and plasma samples were collected from patients undergoing trabeculectomy or cataract surgery and subjected to high-resolution mass spectrometry (HRMS) analysis. Spectral information was processed, and the acquired data were subjected to uni-variate as well as multi-variate statistical analyses using MetaboAnalyst ver5.0. To further understand the localized metabolic abnormalities in glaucoma, metabolites affected in aqueous humor were distinguished from metabolites altered in plasma in this study. Nine and twelve metabolites were found to be significantly altered (p < 0.05, variable importance of projection >1 and log2 fold change ≥0.58/≤ -0.58) in the aqueous humor of PACG and POAG patients, respectively. The galactose and amino acid metabolic pathways were locally affected in the PACG and POAG groups, respectively. Based on the observation of the previous findings, gene expression profiles of trace amine-associated receptor-1 (TAAR-1) were studied in rat ocular tissues. The pharmacodynamics of TAAR-1 were explored in rabbits using topical administration of its agonist, ß-phenyl-ethylamine (ß-PEA). TAAR-1 was expressed in the rat's iris-ciliary body, optic nerve, lens, and cornea. ß-PEA elicited a mydriatic response in rabbit eyes, without altering intraocular pressure. Targeted analysis of ß-PEA levels in the aqueous humor of POAG patients showed an insignificant elevation. This study provides new insights regarding alterations in both localized and systemic metabolites in primary glaucomatous patients. This study also demonstrated the propensity of ß-PEA to cause an adrenergic response through the TAAR-1 pathway.

Elevated histamine levels in aqueous humor of patients with glaucoma.

Purpose: Neurotransmitters (NTs) are the key mediators of essential ocular functions, such as processing the visual functions of the retina, maintaining homeostasis of aqueous humor, and regulating ocular blood flow. This study aims to determine variations in the levels of L-glutamate and γ-aminobutyric acid (GABA), histaminergic, adrenergic, cholinergic, and serotonergic NTs in patients with primary glaucoma versus patients with cataract. Methods: This case-control study involved three age-matched groups of patients with primary open angle glaucoma (POAG, n = 14), primary angle closure glaucoma (PACG, n = 21), and cataract (control, n = 19). Patients' aqueous humor and plasma were collected, snap frozen at -80 °C, and subjected to ultrasensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for quantification of NTs. Results: Baseline intraocular pressure and the cup-to-disc ratio were found to be statistically significantly elevated in the POAG and PACG groups compared to the cataract control group. In aqueous humor, histamine was found to be statistically significantly elevated (5-fold, p<0.0001), whereas 1-methyl histamine was statistically significantly decreased (p<0.05) in POAG compared to the control group. A statistically significant increase in L-glutamate and GABA was observed among both patient groups with glaucoma compared to the cataract control group. Adrenaline was found to be elevated only in the PACG group (2.7-fold, p<0.05). No statistically significant difference was observed among the plasma NT levels between the groups. Conclusions: This study demonstrated the prominent role of the histaminergic system apart from autonomic mechanisms in the progression of glaucoma. Elevated L-glutamate and GABA could be due to retinal ganglionic cell death. Further studies are required to evaluate the effects of histamine on Müller cell dysfunction.

Clinical and ASOCT evaluations of 'bleb-sparing epithelial exchange' in paediatric and adult dysfunctional blebs over 5 years.

PURPOSE: To evaluate the long-term outcome of 'bleb-sparing epithelial exchange' surgery for dysfunctional filtering blebs in paediatric and adult eyes. METHODS: Patients who had undergone bleb revision ≥ 5 years back and were on regular follow-up were included. Age, ocular diagnosis, details of primary filtering surgery including mitomycin-C (MMC) usage, indication and year of bleb revision were recorded. After bleb revision, the mean intraocular pressure (IOP), glaucoma medications and best corrected visual acuity (BCVA) up to 5 years were noted. On last review, clinical details, bleb characteristics and swept source anterior segment tomographic (SSOCT) assessment of bleb were recorded. Comparative analysis of paediatric and adult eyes was performed. MAIN OUTCOME MEASURES: Change in IOP and BCVA. 'Complete success' was defined as IOP ≥ 6 to ≤ 18mmHg without use of any topical glaucoma medications and 'Qualified success' when ≥ 1 topical glaucoma medication(s) was required. RESULTS: A total of 51 eyes of 51 consecutive patients were studied, among which 22 were children. The mean duration between filtering surgery and bleb revision was 4.54 ± 1.53 years in paediatric and 6.48 ± 3.5 years in the adult group, p = 0.04. Children underwent trabeculotomy + trabeculectomy with 0.04% MMC, while adults underwent trabeculectomy with 0.02% MMC. The mean pre-revision IOP was 6.38 ± 2.80 and 6.51 ± 2.78 mmHg in the paediatric and adult group respectively, p = 0.86. At 3 months post-revision, it increased to 11.81 ± 3.48 and 12.75 ± 3.52 mmHg respectively (p < 0.001). At final review, mean IOP of paediatric group was 10.90 ± 2.59 and adult group was 11.86 ± 2.66 mmHg, p = 0.20. At 5 years, complete success was 68.18% and 72.41%, and qualified success was 31.87% and 27.59% in the former and latter group respectively, p = 0.49. No failures were seen. Kaplan-Meier probability at 5 years for IOP target ≤ 18, ≤ 15 and ≤ 12 in children was 95.45%, 63.64% and 50% and in adults 93.10%, 65.52% and 41.38% respectively. BCVA improved up to 1 year in paediatric group, with continued improvement in adults up to 3 years. SSOCT measured bleb height was 0.88 ± 0.37 and 1.32 ± 0.49mm in children versus adults (p = 0.006) and wall thickness, 0.35 ± 0.22 and 0.58 ± 0.24mm respectively, p = 0.008. CONCLUSION: Bleb-sparing epithelial exchange is an equally safe and effective technique with good long-term success in both paediatric and adult dysfunctional blebs.

Severity of visual field defects in primary congenital glaucoma and their risk factors.

PURPOSE: The primary objective of the study was to assess the frequency and severity of visual field defects (VFD) in primary congenital glaucoma (PCG). The secondary objective was to ascertain any associated risk factors. METHODS: An ambispective review of patients with PCG on follow-up with a 'target' intraocular pressure (IOP) of ≤ 15 mmHg. Age, sex, laterality, duration of follow-up, baseline IOP, baseline cup-disc ratio (CDR), central corneal thickness (CCT), age during filtering surgery, second surgery if any, yearly IOP, glaucoma medications and best corrected visual acuity from 2013 (year 1) to the final review and final CDR were noted down. Children ≥ 5 years of age with best corrected visual acuity ≥ 6/60 were subjected to manual kinetic Goldmann perimetry, and visual field defects (VFD) were identified. RESULTS: Seventy-one of 90 eyes completed a reliable kinetic perimetry. The mean age of children was 12.34 ± 4.86 years, and the mean follow-up duration was 10.77 ± 4.69 years. Baseline IOP and CDR were 29.07 ± 8.83 mmHg and 0.66 ± 0.22, respectively. 86.67% of eyes underwent a trabeculotomy + trabeculectomy with mitomycin-C. Thirty-one eyes (34.44%) required a second surgery, 25 of which were bleb revisions and 3 trabeculectomies. Mean IOP and CDR during last visit were 10.23 ± 2.76 mmHg and 0.52 ± 0.25, p < 0.001 as compared with baseline. On Goldmann perimetry, 19 eyes, 26.76%, had defects, arcuate scotoma being most frequent. On the Fisher exact test, a baseline/final CDR > 0.8, undergoing just a trabeculectomy with MMC, needing ≥ 2 glaucoma medications on review or a repeat trabeculectomy was associated with greater severity of VFD. On univariate logistic regression, eyes that needed a bleb revision [OR, 95% CI 9.75 (2.66-35.67), p = 0.001], a repeat trabeculectomy with mitomycin-C [OR (CI) 18 (1.31-245.58), p = 0.03] and final CDR of > 0.8 [OR (CI) 23.1 (3.7-144.21), p = 0.001] were associated with VFD. On multivariable regression analysis, female sex [OR (CI) 18 (2.01-161.04), p = 0.01] was identified as the single most important risk factor for development of a VFD. CONCLUSION: At a 'target' IOP of ≤ 15 mmHg, 26.76% of PCG eyes manifested a VFD over 10 years. Baseline and/or final CDR > 0.8, necessity for ≥2 medications or a repeat glaucoma surgery, and female sex were identified as risk factors for development and greater severity of glaucomatous VFD.

Evaluation of physical properties and dose equivalency of generic versus branded latanoprost formulations.

The purpose of this study was to comparatively evaluate the pharmaceutical characteristics of various marketed generic formulations of prostaglandin analogue latanoprost in the Indian market. Three generics of latanoprost and one branded (Xalatan) formulation (five vials each) were obtained from authorized agents from the respective commercial sourcing having the same batch number. These formulations were coded, and the labels were removed. At a standardized room temperature of 25 °C, the concentration, osmolarity, drop size, pH, and total drops per vial were determined for Xalatan and all the generics of latanoprost. The concentration of various brands varied between 50.49 ± 0.36 and 58.90 ± 0.52 µg/ml as compared to the standard labeled concentration of 50 µg/ml on the latanoprost vials. The concentration of drugs in individual drop varied from 1.30 ± 0.05 to 1.78 ± 0.04 µg/drop. The volume of drug formulation per bottle varied from 2.4 ± 0.12 to 2.6 ± 0.09 ml/bottle. The number of drops per bottle varied from minimum of 88.60 ± 0.10 drops to maximum of 102.0 ± 4.3 drops across all the formulations, while the drop size varied from 25.72 ± 2.70 to 29.97 ± 1.38 µl. The osmolarity of 2/4 drugs was within 300 mOs M (±10 %). The specific gravity varied between 0.98 ± 0.01 and 1.007 ± 0.01, while pH was between 7.05 ± 0.004 and 7.13 ± 0.005. Two of the generic brands were outside the United States pharmacopoeia limits (±10%) for ophthalmic formulation, with concentration exceeding the limits by 3 % (p = 0.151) and 8 % (p = 0.008), respectively. This pilot study highlights that there are significant variations in the drug concentrations and physical properties of generic latanoprost formulations. Although none of the brands had concentrations below the recommended level, two of the brands had concentrations exceeding the limits by 3 and 8 %, respectively.

Comparative evaluation of outcomes of phacoemulsification in vitrectomized eyes: silicone oil versus air/gas group.

The purpose of this study is to comparatively evaluate the morphology of cataract, intraoperative and postoperative complications (IPC), and surgical outcomes of phacoemulsification in post 23G vitrectomized eyes in silicone oil versus air/gas group. This prospective interventional clinical study took place in the Dr. RP Centre for Ophthalmic Sciences, AIIMS, New Delhi, India. Eighty-nine eyes of 89 consecutive vitrectomized patients with cataract were included. All underwent phacoemulsification and evaluated for cataract morphology, surgical difficulties, IPC, visual acuity, and specular count. Mean age of patients was 50.24 ± 15.19 years. There were 65 males and 24 females and 48 eyes in silicone oil group and 41 in air/gas group. Combination type was the commonest morphology seen in both silicone oil (52.08 %) and air/gas group (70.33 %) followed by posterior subcapsular cataract (PSC) in 31.25 % silicone group and 12.2 % air/gas group. Posterior capsular plaque (PCP) was seen in 41.67 % of silicone oil versus 7.32 % air/gas group; p < 0.005. Pupillary abnormalities were significantly more in oil (31.25 %) than in air/gas group (9.76 %); p = 0.014. Mean duration between vitrectomy and phacoemulsification in oil group versus air/gas group was 8.39 ± 4.7 months and 10.9 ± 5.22 months, respectively; p < 0.005. Mean postoperative logMAR visual acuity was better in air/gas (0.43 ± 0.25) than in oil (0.66 ± 0.29) group, p < 0.005. There was no significant difference in mean endothelial cell loss postoperatively in either groups (p = 0.25). Morphology of cataract differs in the two groups with PSC being more common in oil group. The mean time of cataract onset was significantly less in patients with oil group, and poor visual outcome in oil group may be attributable to the increased PCP noted.

Evaluating the long-term efficacy of short-duration 0.1 mg/ml and 0.2 mg/ml MMC in primary trabeculectomy for primary adult glaucoma.

OBJECTIVE: To evaluate safety and efficacy of 0.1 mg/ml versus 0.2 mg/ml mitomycin-C (MMC), applied for 1 min subconjunctivally, during trabeculectomy for primary adult glaucoma in previously un-operated eyes. MATERIALS AND METHODS: This is a randomised controlled, non-inferior, clinical trial consisting of 50 consecutive POAG or CPACG patients uncontrolled on maximal hypotensive therapy, meeting all inclusion criteria. Patients were randomized into two groups and underwent a standard limbus-based trabeculectomy with MMC: Group I, 0.1 mg/ml and Group II, 0.2 mg/ml. The pre-operative and post-operative intraocular pressure (IOP), bleb morphology, and visual acuity were recorded every 6 months for 2 years. Complete success (primary outcome) was defined as IOP ≤ 15 mmHg without any additional medications at the end of 2 years. RESULTS: The average age of patients was 62.6 ± 9.8 years and 61.2 ± 8.1 years in Group 1 and 2, respectively; p = 0.57. The mean preoperative IOP was 22.5 ± 1.4 mmHg and 23.3 ± 1.8 mmHg; p = 0.10. The mean IOP at 2 years was 11.1 ± 1.6 mmHg and 10.8 ± 2.8 mmHg, a mean reduction in IOP of 50.6 ± 1.23 %, and 53.7 ± 2.25 % in Group I and II, respectively. The complete success was 92.0 % and 91.7 % in the two groups, respectively (p = 0.99), and there was one failure (Group II, post trauma). A wider bleb extent and larger areas of thin, transparent conjunctiva over the bleb were seen with the 0.2 mg/ml MMC group (p < 0.001) and in PACG eyes; p < 0.04. CONCLUSION: A 1-min subconjunctival application of low dose 0.1 mg/ml MMC is non-inferior to 0.2 mg/ml and is probably a safer alternative, as thinning of the bleb is significantly less frequent in the long term.

Modified technique of levator plication for the correction of Marcus Gunn jaw-winking ptosis: a case series.

To conduct a study on ptotic eyelids with Marcus Gunn jaw-winking ptosis operated via a technique of modified levator plication, prospective interventional case series. Ten ptotic eyelids with Marcus Gunn jaw-winking phenomenon (MGJWP) underwent modified levator plication surgery. Postoperatively, all cases were followed up for at least 6 months. Outcome parameters included amount of ptosis correction, amount of MGJWP correction, palpebral aperture height, lid lag, and lagophthalmos. The mean amount of ptosis was 4.25 ± 0.79 mm (range of 3-6 mm), mean amount of MGJWP was 5.10 ± 2.27 mm (range 2-9 mm), and the mean levator function was 8.3 ± 2.27 mm (range of 4-12 mm). At 6 months follow-up, good correction of ptosis was seen in nine out of ten patients. Resolution of MGJWP (≤1 mm of excursion of upper eyelid with synkinetic mouth movement) was seen in three patients. Improvement in MGJWP (>1 mm of excursion of upper eyelid with synkinetic mouth movement) was seen in seven patients. The mean post-operative lagophthalmos was 0.80 ± 0.88 mm. The modified levator plication technique was effective in the treatment of MGJWP. This modified technique of levator plication is anatomically less destructive and hence more acceptable, with the added advantages of less post-operative lagophthalmos and no lid contour defects.

Intraoperative optical coherence tomography-guided transconjunctival bleb suturing - A minimally invasive technique for managing overfiltering bleb.

With the recent advancement in technologies, real-time integrated intraoperative optical coherence tomography (iOCT) microscopes are available, which facilitates surgical precision and also reduces the risk of complications. Two glaucoma patients with advanced glaucomatous optic neuropathy, who underwent uneventful trabeculectomy with 0.02% mitomycin C, developed persistent hypotony postoperatively till 4-6 weeks. On clinical examination, visual acuity was 1/60 with low intraocular pressure (IOP) of 4 mmHg. Elevated, overfiltering bleb was seen on slit-lamp examination, along with hypotonous maculopathy. Anterior segment optical coherence tomography (AS-OCT) showed multiple large hyporeflective fluid spaces suggestive of overfiltering bleb. Considering the risk of choroidal detachment and further deterioration of vision, iOCT-guided transconjunctival bleb suturing was planned. iOCT helped to identify the exact location of scleral flap, and transconjunctival suturing was done with successful outcomes in terms of improved IOP and visual acuity.

Congenital pterygium with anterior segment dysgenesis: rare ocular manifestation in Rubinstein-Taybi syndrome.

Pterygium is a benign, wing-shaped fibrovascular overgrowth of subconjunctival tissue that can encroach over the cornea. This condition usually occurs in individuals aged 20-40 years but is rarely seen in children. We report a case of an infant with Rubenstein-Taybi syndrome presenting with nebulo-macular corneal opacity and congenital pterygium. On examination under anaesthesia, bilateral infero-nasal nebulo-macular corneal opacity (6 × 5 mm) with a whitish pink tissue originating from nasal bulbar conjunctiva was noticed. The probe test was negative for this tissue. To the best of our knowledge, only two other cases of congenital pterygium have been reported in the literature. The presence of this anomaly supports the hypothesis of genetic factors having a role in the development of pterygium.

Stress and Allostatic Load in Patients With Primary Open Angle Glaucoma.

PRCIS: This study evaluated the allostatic load (AL) in primary open angle glaucoma (POAG) patients and reported that the AL score was significantly higher in glaucoma patients compared with age-matched controls. PURPOSE: To evaluate the AL in patients with POAG. METHODS: This case-control study comprised 50 POAG (glaucoma patients) and 50 age-matched controls without glaucoma (controls). AL was estimated based on 13 variables: systolic blood pressure (BP), diastolic BP, homocysteine, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, body mass index, serum cortisol, glycosylated hemoglobin, albumin, creatinine clearance, and C-reactive protein. High-risk thresholds were determined based on biological cutoffs of each biomarker. One point was assigned for each biomarker reading above cutoff and were summated to obtain AL score; score ≥4 was considered high. RESULTS: Mean age of glaucoma patients was 60.82±6.26 and 60.14±6.72 years in controls ( P =0.602). All components of AL score (except C-reactive protein) had higher values in glaucoma patients. There was a statistically significant difference in homocysteine ( P =0.001), total cholesterol ( P =0.037), high-density lipoprotein ( P =0.005), and glycosylated hemoglobin ( P =0.003). Mean AL score was 4.68±2.09 in glaucoma patients and 3.32±1.34 in controls ( P <0.001). There was significant association of high AL score with older age ( P =0.006), low socioeconomic status ( P =0.020), and glaucoma severity ( P =0.001). Negative correlation was seen between AL and retinal nerve fiber layer thickness (Right Eye: r =-0.37, P <0.001; Left Eye: r =-0.298, P <0.001) and visual field mean deviation (Right Eye: r =-0.469, P <0.001; Left Eye: r =-0.520, P <0.001). CONCLUSIONS: Glaucoma patients exhibited allostatic overload indicating physiological dysregulation to chronic stress although additional research is required to establish causality. A holistic approach with lifestyle modifications to reduce chronic stress should be an integral part of managing glaucoma patients as it would serve both to possibly reduce or prevent disease progression and improve overall health outcomes.

Endocannabinoids and cortisol in plasma, aqueous and tear samples of primary angle closure glaucoma versus controls.

PURPOSE: To compare the levels of endocannabinoids (EC) in plasma, aqueous humor and tears, cortisol in plasma and aqueous, in primary angle closure glaucoma (PACG) and controls, while comparing the quality of life in both groups. METHODS: A total of 60 patients, ≥40years of age, with a diagnosis of PACG or cataract, 30 in each group were recruited. They were subjected to a detailed ophthalmic evaluation, a WHO Quality of Life Brief Version (WHOQOL-BREF) questionnaire answering and collection of tear, aqueous and blood samples. The levels of endocannabinoids-anandamide (AEA), 2-arachidonoylglycerol (2AG) in plasma, aqueous humor and tears; cortisol in plasma and aqueous humor; and WHO-QOL score in each group were noted. RESULTS: Plasma AEA (p = 0.01) and plasma 2-AG, (p = 0.002) levels were significantly higher in the control group as compared to the PACG group. WHO-QOL score was better in controls (p < 0.001). The EC were in undetectable levels in aqueous. Plasma and aqueous cortisol were significantly higher in PACG and both had the highest Area under the receiver operating characteristics (AUROC) curve value for differentiating PACG from controls. Tear 2AG and tear AEA had a moderately strong positive correlation with plasma 2-AG. Females had insignificantly higher levels of plasma and tear endocannabinoids. CONCLUSIONS: Tear endocannabinoids were determined for the first time in PACG and normal with no difference between the two groups. Plasma and aqueous cortisol levels are a differentiating factor between normal and glaucoma patients with plasma endocannabinoids being remarkably higher in normals. Quality of life in glaucoma patients with high cortisol levels is poorer.

Outcomes of bent ab interno needle goniectomy with phacoemulsification in moderate to severe primary open angle glaucoma.

PURPOSE: To assess the safety and efficacy of bent ab interno needle goniectomy (BANG) in moderate to severe primary open angle glaucoma (POAG) eyes undergoing phacoemulsification (phaco). DESIGN: Single-arm, prospective, interventional study. METHODS: POAG patients with medically uncontrolled intraocular pressure (IOP), >15 mmHg for moderate and >12 mmHg for severe POAG, with visually significant cataract were recruited. All patients underwent BANG using a 26-gauge needle to excise 30° of the trabecular meshwork, along with phaco. Primary outcome was IOP. Secondary outcomes were success rate, percentage reduction in IOP/antiglaucoma medications (AGMs), and intraoperative complications. Success at 12 months was defined as: criterion A: IOP <15 mmHg for moderate glaucoma or <12 mm Hg for severe glaucoma with or without AGMs OR criterion B reduction in number of AGMs by >1. RESULTS: Thirty-two eyes of 32 patients underwent BANG + phaco. Mean age of the participants was 62.7 ± 8.4 years and there were 25 males and seven females. At 12 months, a significant decrease was noted in both IOP (from 17.6 ± 3.6 to 12 ± 1.6 mmHg, 31.8%; P < 0.001) and AGMs (from 3.7 ± 0.9 to 2.8 ± 0.8, 24.3%; P < 0.001). Twenty percent or more reduction in IOP was achieved in 62.5% (20/32) of eyes. Overall success (meeting either of the criteria A or B) at 12 months was achieved in 87.5% eyes. Mild postoperative hyphema was noted in 10 (31.2%) eyes, and two eyes (6.2%) required additional filtration surgery at 7 months. CONCLUSION: A 30-degree BANG with phaco in patients of POAG appears to be a safe, effective and affordable MIGS for developing countries.

Clinical applications of aqueous angiography in glaucoma.

Aqueous humor outflow (AHO) pathways are the main site of resistance causing elevated intraocular pressure in glaucoma, especially primary open-angle glaucoma patients. With the recently introduced technique of aqueous angiography (AA); functional, real time assessment of AHO from proximal (trabecuar meshwork) to distal pathways under physiological conditions has been made possible. AHO pathways are segmental, and AA can identify high-flow region (increased angiographic signals) and low flow region (decreased angiographic signals) in an individual. With the introduction of canal-based minimally invasive glaucoma surgeries (MIGS), the assessment of AHO can help guide the placement of stents/incisions during MIGS procedures. This can allow individualized and targeted MIGS procedures in glaucoma patients for better results. Based on the density of AHO pathways visualized on AA, surgeons can decide whether to perform MIGS or conventional glaucoma surgery for improved outcomes for the patient. Immediate intraoperative assessment for functionality of the MIGS procedure performed is possible with AA, allowing for surgical adjustments of MIGS procedure in the same sitting, if needed. This review provides a summary of the studies performed with AA to date, with a special focus on Indian patients. It covers the basics and clinical applications of AA for improving surgical outcomes in glaucoma patients.

Evaluation of Visual Cortex Activity using Functional Near-Infrared Spectroscopy (fNIRS) in Primary Open Angle and Primary Angle Closure Glaucoma: A pilot study.

PRECIS: Functional Near Infrared Spectroscopy was used to assess visual cortical activity in patients with primary open angle and primary angle closure glaucoma. There was decreased activity in the visual cortex of glaucoma patients correlating with the severity of glaucoma. PURPOSE: To evaluate visual cortex activity using fNIRS (Functional Near Infrared Spectroscopy) in primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) compared to healthy controls. METHODS: A total of 30 POAG, 31 PACG, and 30 healthy aged-matched controls from a single centre were recruited in this cross-sectional observational pilot study with purposive sampling. The POAG and PACG groups were age-matched but were not matched for disease severity at recruitment. All participants underwent fNIRS testing using a multi-channel continuous-wave near infra-red system NIRSport 8×7 device (NIRx Medizintechnik GmbH, Berlin, Germany). The visual cortex activity was evaluated in terms of maximum amplitude of change in oxyhemoglobin (OxyHb) concentration over 10 seconds and a comparison was done between three groups. Both POAG and PACG groups were combined (termed as glaucoma group) to assess relationship of visual cortical activity with disease severity {by visual field defect (mean deviation) and retinal nerve fiber layer (RNFL) thickness}. RESULTS: All participants showed the characteristic response of increased OxyHb and decreased DeoxyHb during stimulus presentation. The maximum amplitude of change in OxyHb concentration over 10 seconds was significantly lower in both POAG and PACG groups compared to control in the right and left middle occipital gyri (P<0.05). There was no significant difference between PACG and POAG. Importantly, there was a negative correlation of the visual cortex activity with the visual field defects (mean deviation) (P<0.05) and a positive correlation with RNFL thickness in the glaucoma group (P<0.05). CONCLUSION: In glaucoma patients, reduction in visual cortical activity was observed which may be indicative of neuronal degeneration occurring in the occipital cortex. Disease severity in glaucoma appears to be closely correlated with visual cortex activity. fNIRS can serve as a useful neuroimaging modality for assessing the hemodynamic and neurodegenerative changes in glaucoma.

Changes in confocal microscopy in glaucoma patients after intraocular pressure reduction with medical therapy.

PURPOSE: Topical glaucoma medication is the first line of management to reduce intraocular pressure (IOP) in patients with glaucoma. In this study, we intended to compare the ultrastructural findings of the cornea in patients with glaucoma before and after the reduction of the IOP through confocal microscopy. METHODS: Ten patients (19 eyes) with newly diagnosed glaucoma were recruited from the glaucoma services of our tertiary care center. Demographic parameters were noted, and basic ocular examination, specular microscopy (Topcon SP3000P, Tokyo, Japan), and ultrasonic pachymetry (300 AP, Sonomed Escalon, Stoneham, MA, USA) were performed. In vivo confocal microscopy of corneal sections was performed using the z-ring Confoscan 4.0 (Nidek, Inc., Freemont, CA) at baseline and after 3 months of starting glaucoma medications. RESULTS: The mean age of the patients was 53.53 ± 9.34 years. There was a statistically significant reduction ( P < 0.0001) of IOP from 30.21 ± 7.42 mmHg (baseline) to 16.42 ± 4.14 mmHg (3 months). The mean central corneal thickness at baseline was 533.42 ± 3.96 µm, and it further decreased to 521.94 ± 42.45 µm at the end of 3 months ( P = 0.006). No significant change was noted in the mean epithelial cell density, mean keratocyte density in anterior and posterior stroma, and the mean endothelial cell density and cell area ( P >0.5). There was no significant percentage change in these parameters before and after the lowering of the IOP. CONCLUSION: A short-term (3 months) decrease in IOP using topical glaucoma medications caused a significant reduction in corneal thickness but did not have any significant ultrastructural changes in cornea measured using confocal microscopy.

Effect of "365 Breathing Technique" on Intraocular Pressure and Autonomic Functions in Patients With Glaucoma: A Randomized Controlled Trial.

PRCIS: Patients with primary open angle glaucoma were advised to follow the "365 breathing technique" for 6 weeks in addition to their pharmacological glaucoma treatment. It helped to reduce intraocular pressure (IOP), stress biomarker-cortisol, and improve autonomic dysfunction. OBJECTIVE: To study the effect of the "365 breathing technique" on IOP, autonomic functions, and stress biomarkers in patients with primary open angle glaucoma. METHODS: In this randomized, controlled, interventional trial, after randomization, 40 patients in the intervention group followed "365 breathing" (three times a day, breathing rate: 6 cycles/min for 5 min) in addition to their pharmacological glaucoma treatment and 40 patients in the control group continued only with their pharmacological glaucoma treatment. IOP, serum cortisol, heart rate variability (HRV), and heart rate response to deep breathing test (DBT) were recorded at preintervention and 6 weeks postintervention. RESULTS: The mean IOP, serum cortisol, parameters of the HRV test, and DBT were comparable between the two groups at baseline. At the 6-week follow-up, in the intervention group, mean IOP was significantly lower (16.09 ± 2.24 vs 18.38 ± 1.58 mm Hg, P = 0.03) and serum cortisol were significantly lower (13.20 ± 3.11 vs 14.95 ± 2.60 mcg/dL, P = 0.038) compared with the control group. In the HRV test, time domain analysis showed a significant difference in the root mean square of the successive difference between RR interval values between both groups at 6 weeks ( P = 0.015) pointing towards higher postintervention parasympathetic activation in the intervention group. In frequency domain analysis (HRV test), the ratio of the low-frequency component to the high-frequency component was significantly lower in the intervention group at 6 weeks (1.65 vs 1.79, P = 0.019) indicating a shift in sympathovagal balance towards greater vagal modulation.There was a significant increase in delta heart rate ( P = 0.019) and expiratory:inspiratory ratio ( P = 0.011) in the intervention group at 6 weeks when compared with baseline values, indicating improved parasympathetic reactivity to DBT. CONCLUSION: "365 breathing" technique can reduce IOP and serum cortisol, and improve autonomic dysfunction in patients with glaucoma.

Encapsulated bleb with scleral fistula - A diagnostic dilemma treated by a simple procedure.

We present a case of post-trabeculectomy encapsulated dysesthetic bleb with scleral fistula, managed successfully with autograft. The child was operated on twice before for trabeculectomy, and intraocular pressure (IOP) recorded was in the normal range for the initial few years. This time child presented with a large encapsulated dysesthetic bleb with borderline IOP. As the IOP was on the lower side, an underlyings cleral fistula was suspected and planned for bleb revision with a donor patch graft. We describe the novel technique of bleb revision along with the repair of the scleral fistula with an autologous free fibrotic Tenon's tissue graft instead of a donor patch graft with a successful outcome.