Progression to bilaterality in unilateral primary congenital glaucoma.

PURPOSE: To evaluate the incidence of rise in intraocular pressure (IOP) in fellow eyes of patients with unilateral primary congenital glaucoma (PCG) and to identify risk factors for IOP increase over long-term follow-up. METHODS: The medical records of unilateral PCG patients who had completed at least 5 years of follow-up were reviewed retrospectively. The incidence of developing ocular hypertension / glaucoma in fellow eyes was analyzed. Fellow eye progressors were those which showed an increase in optic nerve cupping by at least 0.2 since the first presentation or had IOP of >21 mm Hg on two occasions. The risk factors for progression that were analyzed included IOP, visual acuity, axial length, central corneal thickness (CCT), corneal diameters (CD), presence or absence of angle dysgenesis on high-resolution anterior segment optical coherence tomography (AS-OCT), and morphology of aqueous outflow pathways. RESULTS: After a median follow-up of 8.2 years (range, 5-25.5) progression to bilateral disease was found in 17 of 54 patients (32%), of whom 8 (15%) developed ocular hypertension and 9 (17%) developed glaucoma in the fellow eye. Among the unaffected fellow eyes, those with a larger CD (>12 mm), measured after at least 5 years' follow-up, were ten times more likely to progress (P = 0.01; OR = 9.5 [95% CI, 1.7-54.3]). The presence of a patent supraciliary channel was significantly more frequently associated in fellow eyes compared with affected eyes on AS-OCT (OR = 1.4 [95% CI, 0.46-4.68]). CONCLUSIONS: One-third of unaffected fellow eyes of unilateral PCG eventually progress over time, most often after 5 years. Larger CD at follow-up in the fellow eye is strongly predictive for progression.

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.

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.

Early Drainage of Suprachoroidal Hemorrhage Combined with Surgical Correction of Hypotony after Trabeculectomy.

Aims and background: Delayed suprachoroidal hemorrhage (DSCH) is a vision-threatening complication of intraocular surgeries with a higher prevalence in postglaucoma filtering surgeries. Through these case series of trabeculectomy complicated with DSCH, we aim to emphasize that correction of hypotony (inciting factor) is fundamental for complete resolution and prevention of recurrence. Case description: All three glaucoma patients underwent trabeculectomy surgery followed by DSCH on postoperative day 1. Drainage of DSCH using a 23 gauge trocar cannula within 48 hours of onset was performed along with exploration for the cause of hypotony. All three patients had satisfactory visual and anatomical outcomes. Conclusion: Early drainage using 23 gauge trocar cannulas gives good results in DSCH. The cause of hypotony must simultaneously be corrected during the drainage of DSCH. Preventive measures against hypotony should be taken while doing glaucoma filtering surgery. Clinical significance: Surgical exploration for the cause of hypotony must simultaneously be performed during drainage of DSCH. Primary preventive measures against hypotony and bleeding during glaucoma filtering surgeries, like the use of releasable sutures, viscoelastic in the anterior chamber, and discontinuation of anticoagulants, can be done. Early drainage using trocar cannulas gives satisfactory results in DSCH postglaucoma surgeries. How to cite this article: Beri N, Verma S, Bukke AN, et al. Early Drainage of Suprachoroidal Hemorrhage Combined with Surgical Correction of Hypotony after Trabeculectomy. J Curr Glaucoma Pract 2024;18(1):23-27.

Analyzing the Shortcomings of Trabecular Micro-bypass Stents for Surgical Management of Glaucoma.

How to cite this article: Dada T, Beri N. Analyzing the Shortcomings of Trabecular Micro-bypass Stents for Surgical Management of Glaucoma. J Curr Glaucoma Pract 2024;18(1):1-3.

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.

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.

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.

Beyond the optic nerve: Genetics, diagnosis, and promising therapies for glaucoma.

Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle glaucoma with subtypes like POAG, ACG, XFG, PCG, PDG, and developmental glaucoma. The pathophysiological and genetic factors behind glaucoma remain partially understood, with past studies linking intraocular pressure (IOP) levels to retinal ganglion cell death. Open-angle glaucoma involves elevated resistance to aqueous outflow via the trabecular meshwork, while angle-closure glaucoma typically sees drainage pathways obstructed by the iris. Genes have been identified for POAG, ACG, XFG, PCG, PDG, and developmental glaucoma, allowing for early-onset detection and the emergence of gene therapy as an effective treatment. Nevertheless, diagnostic and treatment options have their constraints, necessitating large-scale, well-designed studies to deepen our grasp of genetics' role in glaucoma's pathogenesis. This review delves into glaucoma's risk factors, pathophysiology, genetics, diagnosis, and available treatment options, including gene therapy. Additionally, it suggests alternative therapies like yoga and meditation as adjunct treatments for glaucoma prevention. Overall, this review advances our comprehension of the pathophysiology and genetic associations of glaucoma while highlighting the potential of gene therapy as a treatment avenue. Further research is imperative to fully elucidate the genetic mechanisms underpinning glaucoma and to devise effective treatments.

Toxic anterior segment syndrome (TASS): A review and update.

Toxic anterior segment syndrome (TASS) is an acute, sterile, postoperative inflammatory reaction of the anterior segment without vitreous involvement, following an uncomplicated and uneventful ocular surgery, having broad and multiple etiologies. The symptoms of decreased visual acuity and ocular discomfort generally occur within the first 12-48 h after intraocular surgery. The clinical signs include prominent limbus-to-limbus corneal edema, anterior chamber cells, aqueous flare, fibrinous inflammation, and/or keratic precipitates. There can be sight-threatening complications of TASS, such as permanent corneal decompensation, intractable glaucoma, and cystoid macular edema. The causes of TASS are emerging and being reported, so are the newer treatment options for managing the inflammation and its complications. Prevention guidelines for TASS are being updated, and a traceability system for surgical instruments and intraocular fluids used during the surgery is being perpetually developed. It is important to recognize TASS and start treatment on an immediate effect. Hereby, we review the literature on TASS, emphasizing its etiology, pathophysiology, management, prognosis, complications, and the importance of prevention as well as prompt recognition.

Primary congenital glaucoma: An iridotrabeculodysgenesis?

PURPOSE: To analyze primary congenital glaucoma (PCG) anterior chamber and angle anomalies over 360° as possible biomarkers of severity and prognosis. METHODS: A cross-sectional observational study was conducted analyzing anterior segment anomalies of PCG patients over 4 years of age who underwent trabeculectomy combined with trabeculotomy and age-matched controls using anterior segment optical coherence tomography (ASOCT), CASIA-2. Anterior iridotrabecular adhesions or anterior iris insertion was identified and quantified from the scleral spur using the iridotrabecular contact (ITC) index parameter as a surrogate. RESULTS: There was a variable but significantly increased anterior iridotrabecular adhesion on ITC index, ITC area, corneal volume, anterior chamber volume, iris volume, anterior chamber depth, and small/absent trabecular meshwork in PCG eyes compared to control eyes. In PCG eyes, anterior iridotrabecular adhesion had a positive correlation with pre-operative central corneal thickness (CCT) (r = 0.53, P = 0.02), review iris thickness (r = 0.4, P = 0.04), and ITC area (r = 0.85, P < 0.001). Review iris thickness had a negative correlation with pre-operative vertical cup-disc ratio (r = -0.51, P = 0.008). Iris hypoplasia with fewer or absent folds, collarette, pupillary ruff, and pupillary ruff to collarette distance was significantly different from controls. CONCLUSION: ASOCT in PCG eyes has shown that they have variable anterior iridotrabecular tissue adhesions, anomalous tissue/membranes in the angle, and iris hypoplasia correlating with pre-operative cup-disc ratio. These features could be used as gonioscopic and clinical biomarkers to assess the severity and prognosis of the disease. The presence of abnormal iris morphology and iridotrabecular tissue anomalies in PCG suggests that it is more than just isolated trabeculodysgenesis and is probably best considered as part of the anterior segment dysgenesis spectrum.

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.

Oral doxycycline for early bleb leak after trabeculectomy: A case report and review of literature.

We report the adjuvant role of oral doxycycline therapy for the management of early bleb leaks post mitomycin-augmented trabeculectomy. Two glaucoma patients, who underwent trabeculectomy with mitomycin C, presented with a low intraocular pressure (IOP) in the early postoperative period. Both patients had moderately elevated bleb with Seidel's positive test. Oral doxycycline 100 mg twice daily was given for 1 week in addition to routine postoperative management. Post doxycycline therapy at 1 week, healing of the wound was noted, with a negative Seidel's test. The IOP was maintained at 3 months postoperatively in both patients.

Optimizing Glaucoma Care: A Holistic Approach.

How to cite this article: Dada T, Chauhan N. Optimizing Glaucoma Care: A Holistic Approach. J Curr Glaucoma Pract 2023;17(3):111-112.

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.

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.