Aim: Understanding the mechanism of fluid outflow by comparing the subconjunctival and subtenon spaces can lead to improved ocular therapeutics. The purpose of the current study is to evaluate subconjunctival vs subtenon lymphatic outflow by creating tracer-filled blebs in each location. Methods: Porcine (n = 20) eyes received subconjunctival or subtenon injection(s) of fixable and fluorescent dextrans. Blebs were angiographically imaged using a Heidelberg Spectralis ([Heidelberg Retina Angiograph] HRA + OCT; Heidelberg Engineering) and bleb-related lymphatic outflow pathways were counted. Optical coherence tomography (OCT) imaging of these pathways was used to assess structural lumens and the presence of valve-like structures. Furthermore, a comparison between tracer injection locations (superior/inferior/temporal/nasal) was made. Histologic analyses for subconjunctival and subtenon outflow pathways were performed, to confirm tracer co-localization with molecular lymphatic markers. Results: Subconjunctival blebs demonstrated a greater number of lymphatic outflow pathways compared to subtenon blebs in every quadrant [superior: 6.10 ± 1.18 (subconjunctival) vs 0.50 ± 0.27 (subtenon); temporal: 2.30 ± 0.40 vs 0.10 ± 0.10; nasal: 5.30 ± 0.60 vs 0.30 ± 0.21; inferior: 6.00 ±1.29 vs 0.1 ± 0.1; all comparisons p < 0.001]. For subconjunctival blebs, the temporal quadrant showed fewer lymphatic outflow pathways compared to the nasal side (p = 0.005). Discussion: Subconjunctival blebs accessed greater lymphatic outflow compared to subtenon blebs. Furthermore, regional differences existed, with fewer lymphatic vessels temporal than at the other locations. Clinical significance: Aqueous humor drainage after glaucoma surgery is incompletely understood. The present manuscript adds to our understanding of how lymphatics might influence filtration bleb function.

Aim: To report the efficacy of the revision of failed ab interno canaloplasty with micro-invasive suture trabeculotomy (MIST) over a follow-up period of 24 months. Materials and methods: A retrospective analysis was performed on 23 eyes with open-angle glaucoma (OAG), on whom an ab interno canaloplasty revision with MIST was performed for glaucoma progression. The primary outcome was the proportion of eyes with a significant intraocular pressure (IOP) reduction at 12 months post trabeculotomy, defined as an IOP ≤ 18 mm Hg or ≥20% reduction in IOP without any secondary intervention (SI), and with the same or fewer number of glaucoma medications (NGM). All parameters, including best corrected visual acuity (BCVA), IOP, NGM, and SI, were evaluated at 1, 6, 12, 18, and 24 months. Results: At 12 months, eight out of 23 eyes (36.4%) achieved complete success, maintained in six eyes (27.3%) at 24 months. A significantly lower mean IOP was recorded at all visits [14.3 ± 4.0 mm Hg at 24 months vs 23.1 ± 6.8 mm Hg at baseline (BL)] with a percent IOP change of up to 27.3% at 24 months postoperatively. NGM and BCVA did not significantly decrease from BL. A total of 11 eyes (47.8%) needed an SI throughout the follow-up period. Conclusion: Ab interno trabeculotomy in patients with failed canaloplasty was not shown to be effective in providing a satisfactory control of IOP in OAG patients, possibly due to the small suture gauge used in the initial canaloplasty. Clinical significance: Further research is needed to optimize the surgical outcome.

Aim: To evaluate mitochondrial genome alterations, cytochrome C oxidase (COX) activity, and oxidative stress in primary open-angle glaucoma (POAG). Methodology: Whole mitochondrial genome was screened in 75 POAG cases and 105 controls by polymerase chain reaction (PCR) sequencing. COX activity was measured from peripheral blood mononuclear cells (PBMCs). A protein modeling study was done to evaluate the impact of G222E variant on protein function. Levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane (8-IP), and total antioxidant capacity (TAC) were also measured. Results: A total of 156 and 79 mitochondrial nucleotide variations were found in the cohort of 75 POAG patients and 105 controls, respectively. Ninety-four (60.26%) variations spanned the coding region, and 62 (39.74%) variations spanned noncoding regions (D-loop, 12SrRNA, and 16SrRNA) of mitochondrial genome in POAG patients. Out of 94 nucleotide changes in coding region, 68 (72.34%) were synonymous changes, 23 (24.46%) non-synonymous, and three (3.19%) were found in the region coding for transfer ribonucleic acid (tRNA). Three changes (p.E192K in ND1, p.L128Q in ND2, and p.G222E in COX2) were found to be pathogenic. Twenty-four (32.0%) patients were positive for either of these pathogenic mitochondrial deoxyribonucleic acid (mtDNA) nucleotide changes. Majority of cases (18.7%) had pathogenic mutation in COX2 gene. Patients who harbored pathogenic mtDNA change in COX2 gene had significantly lower levels of COX activity (p < 0.0001) and TAC (p = 0.004), and higher levels of 8-IP (p = 0.01) as compared to patients who did not harbor this mtDNA. G222E changed the electrostatic potential and adversely impacted protein function of COX2 by affecting nonpolar interactions with neighboring subunits. Conclusion: Pathogenic mtDNA mutations were present in POAG patients, which were associated with reduced COX activity and increased levels of oxidative stress. Clinical significance: POAG patients should be evaluated for mitochondrial mutations and oxidative stress and may be managed accordingly with antioxidant therapies.

Aim: To investigate the long-term efficacy of adjunctive use of latanoprostene bunod (LBN), a new nitric oxide donating prostaglandin medication, in refractory cases of glaucoma at a tertiary care center. Materials and methods: A review for patients who received add-on LBN was conducted from 1^st January 2018 to 31^st August 2020. A total of 33 patients (53 eyes) met the inclusion criteria of being on ≥3 topical medications, having an intraocular pressure measurement prior to starting LBN, and having adequate follow-up. Baseline demographics, prior treatments, adverse effects, and intraocular pressures measured at baseline, 3, 6, and 12 months were recorded. Results: Mean baseline intraocular pressure (IOP) [mm Hg ± standard deviation (SD)] was 19.9 ± 6.0. At 3 months, 49 eyes had a mean IOP of 17.3 ± 5.5 (p < 0.01) with an absolute reduction of 2.6 ± 6.6 and a percent reduction of 9 ± 28%. At 6 months, 35 eyes had a mean IOP of 17.2 ± 4.7 (p < 0.01) with an absolute reduction of 3.6 ± 7.4 and a percent reduction of 11 ± 30%. At 12 months, 28 eyes had a mean IOP of 16 ± 4.5 (p < 0.01) with an absolute reduction of 5.8 ± 7.4 and a percent reduction of 19 ± 38%. Over the course of the study, 18 eyes were lost to follow-up. Three eyes had a laser trabeculoplasty, and four eyes required incisional surgery. No eyes discontinued the medication due to adverse effects. Conclusion: Adjunctive use of LBN in refractory glaucoma showed clinically and statistically significant IOP reductions at 3, 6, and 12-month time points. IOP reduction in patients was stable throughout the course of the study, with the largest decreases seen at the 12-month interval. Clinical significance: LBN was well tolerated by patients and may be useful as an additive agent in providing long-term intraocular pressure reduction for patients with severe glaucoma on maximal therapy.

Importance: Most frequent worldwide cause of permanent blindness is glaucoma. Early in the course of the disease, glaucoma affects many patients without any symptoms. In order to examine for indications of glaucoma and to ascertain whether systemic illnesses or drugs can raise a patient's risk of developing glaucoma, primary care practitioners should be aware of which patients to send to an eye care specialist. A review of the pathogenesis, risk factors, screening, disease monitoring, and treatment options for open-angle and narrow-angle glaucoma are included. Observations: The optic nerve and retinal nerve fiber layer (rNFL) are damaged in glaucoma, a chronic, progressive optic neuropathy that can result in a permanent loss of peripheral or central vision. The only risk factor that is known to be controllable is intraocular pressure (IOP). A family history of glaucoma, older age, and non-white race are additional significant risk factors. Numerous systemic diseases and drugs, such as corticosteroids, anticholinergics, certain antidepressants, and topiramate, can put people at risk of developing glaucoma. Open-angle and angle-closure glaucoma are the two main types of disease. Measurement of IOP, perimetry, and optical coherence tomography are diagnostic procedures to evaluate glaucoma and track the course of the condition. In order to treat glaucoma, IOP must be decreased. This is possible with a variety of glaucoma medication classes, laser surgery, and incisional surgery. Verdicts and relevance: By identifying systemic illnesses and drugs that raise a patient's chance of developing glaucoma and referring high-risk individuals for a thorough ophthalmologic examination, vision loss from glaucoma can be reduced. Clinicians should make sure that patients continue taking their glaucoma drugs as prescribed and should keep an eye out for any negative side effects from any medical or surgical procedures used to treat glaucoma.

Glaucoma is one of the leading causes of irreversible blindness in the world. Although numerous factors have been implicated in the pathogenesis of glaucoma, the main focus of management still remains lowering the intraocular pressure (IOP) by medical or surgical therapy. However, a major challenge is that many glaucoma patients continue to progress despite good control of IOP. In this regard, the importance of other coexisting factors that may contribute to disease progression needs to be explored. Ophthalmologists need to be aware of ocular risk factors and the impact of systemic diseases and their medications, along with lifestyle modifications on the course of glaucomatous optic neuropathy and adopt a holistic approach in treating the eye as well as the patient to alleviate the suffering from glaucoma in a comprehensive manner.

Aim: We report a case of successful intraocular pressure (IOP) management in a patient with refractory primary open-angle glaucoma (POAG) following implantation of XEN gel implant in the same hemisphere as prior failed filtering surgeries [i.e., Baerveldt glaucoma implant (BGI) and trabeculectomy bleb)]. Background: Glaucoma is a major cause of blindness worldwide and is typically associated with elevated IOP and retinal ganglion cell loss. Treatment centers around decreasing IOP with eye drops and surgical interventions. The advent of minimally invasive glaucoma surgeries (MIGS) has expanded therapeutic options for patients who have failed traditional treatments. The XEN gel implant creates a shunt between the anterior chamber and the subconjunctival or sub-tenon's space, allowing for drainage of aqueous humor without significant tissue disruption. Given that the XEN gel implant also results in bleb formation, it is generally recommended to avoid placement in the same quadrant of prior filtering surgeries. Case description: A 77-year-old man with a 15-year history of severe POAG of OU presents with persistently elevated IOP despite multiple filtering surgeries and maximal eye drop regimen. The patient had a superotemporal BGI in OU and a scarred trabeculectomy bleb superiorly in the right eye (OD). He underwent an open conjunctiva ab externo XEN gel implant placement in the OD in the same hemisphere as previous filtering surgeries. At 12 months postoperatively, the IOP range continues to be maintained within goal without complications. Conclusion: The XEN gel implant can be successfully placed in the same hemisphere as prior filtering surgeries and can achieve goal IOP without any surgical complications at 12 months postoperatively. Clinical significance: A XEN gel implant can effectively lower patients’ IOP and can be a unique surgical option in refractory cases of POAG with multiple failed filtering surgeries, even when inserted in close proximity to prior filtering surgeries.

Aim: To report a large hyphema following femtosecond laser-assisted cataract surgery (FLACS) and trabectome resulting in endocapsular hematoma. Background: Hyphema has previously been described following trabectome, however, no cases have been reported following FLACS or FLACS combined with microinvasive glaucoma surgery (MIGS). We report a case of a large hyphema following FLACS combined with MIGS that resulted in an endocapsular hematoma. Case description: A 63-year-old myopic female with exfoliation glaucoma underwent FLACS with a trifocal intraocular lens implant and Trabectome in the right eye. Significant intraoperative bleeding ensued following the trabectome and was treated with viscoelastic tamponade, anterior chamber (AC) washout, and cautery. The patient developed a large hyphema with intraocular pressure (IOP) rise that was treated with multiple AC taps, paracentesis, and eye drops. The hyphema took approximately 1 month to completely clear, leaving an endocapsular hematoma. This was treated successfully with Neodymium:Yttrium-Aluminum-Garnet (Nd:YAG) laser posterior capsulotomy. Conclusion: Hyphema may occur with angle-based MIGS in combination with FLACS and may cause endocapsular hematoma. An increase in episcleral venous pressure during the docking and suction phase of the laser may predispose to bleeding. Endocapsular hematoma is an uncommon finding after cataract surgery and may be treated with Nd:YAG posterior capsulotomy.

Aim: To describe a case of an acute attack of glaucoma due to scleral melting in the area where a trabeculectomy was previously done. This condition resulted from the blockage of the surgical opening due to an iris prolapse in an eye that was previously supplemented with mitomycin C (MMC) during a filtering surgery and bleb needling revision. Case description: A 74-year-old Mexican female with a prior glaucoma diagnosis who assisted to an appointment presenting an acute ocular hypertensive crisis after several months of adequately controlled intraocular pressure (IOP). Ocular hypertension had been regulated after undergoing a trabeculectomy and bleb needling revision; both supplemented with MMC. The severe IOP increase occurred due to uveal tissue blockage in the filtering site, related to melting of the sclera in the same area. The patient was successfully treated through the use of a scleral patch graft and the implantation of an Ahmed valve. Conclusion: An acute attack of glaucoma associated with scleromalacia after trabeculectomy and needling has not been previously reported and is currently attributed to MMC supplementation. Nevertheless, the use of a scleral patch graft and further glaucoma surgery seems to be an efficient way to treat this condition. Clinical significance: Even though this complication was appropriately managed with this patient, we want to prevent further cases like this through the judicious and careful use of MMC.

Aim: To report a case of uveitis-glaucoma-hyphema (UGH) syndrome secondary to a tilted toric intraocular lens (IOL). Background: Over the past few decades, upgrades in lens design, surgical techniques, and posterior chamber IOLs have drastically decreased the incidence of UGH syndrome. We present a rare case of UGH syndrome developing 2 years after a seemingly uneventful cataract surgery and its subsequent management. Case description: A 69-year-old female presented with episodes of sudden visual disturbance in her right eye 2 years after a seemingly uneventful cataract surgery with placement of a toric IOL. Workup included ultrasound biomicroscopy (UBM), which revealed a tilted IOL and confirmed haptic-induced iris transillumination defects consistent with the diagnosis of UGH syndrome. The patient underwent surgical repositioning of the IOL, which led to the resolution of UGH. Conclusion: Uuveitis-glaucoma-hyphema developed from a tilted toric IOL inducing posterior iris chaffing. Careful examination and UBM revealed the IOL and haptic out of the bag position, which was critical in determining the underlying UGH mechanism. The surgical intervention led to the resolution of UGH syndrome. Clinical significance: In patients with a history of uneventful cataract surgery who develop UGH-like symptoms, continued examination of implant orientation and haptic position is critical in preventing the need for future procedures.