Ocular severe involvement in oculofaciocardiodental syndrome: Description of a case series.

BACKGROUND: Oculofaciocardiodental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental, and cardiac systems, being an X-linked condition caused by pathogenic variants in the BCL-6 corepressor gene (BCOR). We report a case series of three female patients with OFCD syndrome with severe glaucoma. RESULTS: Three female patients with OFCD syndrome with different variants involving BCOR gene, in heterozygosity: a seven-years-old girl with an insertion (c.2037_2038dupCT), a nine years-old girl with a microdeletion in the X (p21.2-p11.4)) spanning the BCOR gene; and a 25 years-old female with a deletion (c.3858_3859del). Systemic involvement is variable among patients ranging from one patient mainly with ocular and dental involvement to one with associated intra-auricular and intra-ventricular defects. All the patients presented with congenital cataracts diagnosed in the first days of life. Cataract surgery was performed without incidents between 6 and 16 weeks of age in all the patients. Postoperatively, the three patients developed ocular hypertension and glaucoma with the need for surgical interventions, including trabeculectomy, Ahmed valve implantation, and cyclophotocoagulation. CONCLUSION: OFCD syndrome characterizes by a severe ocular involvement with glaucoma as a characteristic feature. Ocular hypertension after cataract surgery in these patients is challenging, almost always needing surgery during childhood. Therefore, we consider BCOR disruption may predispose to a higher incidence of glaucoma due to its aggressiveness and early onset on our case series. The awareness of these complications is crucial to an adequate follow-up of the patients.

Silicone Oil-Induced Ocular Hypertension Glaucoma Model (SOHU) in Rodent and Nonhuman Primate.

In this chapter, we describe a clinically relevant inducible and reversible ocular hypertension glaucoma model, which mimics the secondary glaucoma that can be a postoperative complication when silicone oil (SO) is used as a tamponade agent in human vitreoretinal surgery. First, we detail the procedures for generating SO-induced ocular hypertension (SOHU) in mouse and describe the two variations of this model that simulate common but distinct glaucoma types. We also describe separately the related procedures for measuring IOP and removing SO to return IOP to normal. Lastly, we describe the extension of the SOHU model in nonhuman primate (NHP), which recapitulates the severe neurodegeneration of acute human glaucoma but with unique dynamic changes of IOP due to the tolerance of the NHP ciliary body. The SOHU glaucoma model is, therefore, suitable for assessing experimental therapies for neuroprotection and regeneration, with or without treatment to lower IOP (SO removal), and consequently for translating relevant findings into novel and effective clinical treatments for glaucoma and other neurodegenerations. This model is straightforward, does not require special equipment or repetitive procedures, closely simulates clinical situations, and may be applicable to diverse animal species although minor modifications may be required.

Real life experience following combined excimer laser trabeculostomy and phacoemulsification in eyes with ocular hypertension or mild glaucoma and cataract.

OBJECTIVES: To assess the efficacy and safety of combined phacoemulsification and excimer laser trabeculostomy (ELT) in eyes with cataract and mild controlled glaucoma or ocular hypertension (OHT). METHODS: Single-centre analysis of eyes that underwent phacoemulsification and ELT between 2017 and 2021. Change in intraocular pressure (IOP), glaucoma medication requirements, corrected distance visual acuity (CDVA), complications and re-interventions were evaluated. Success was defined as a reduction ≥20% from preoperative IOP, an IOP ≤ 14 mmHg or a reduction in glaucoma medication requirements with an IOP equal or lower than the preoperative IOP. RESULTS: Mean follow-up was 658 ± 64 days. Mean preoperative IOP was 17.76 ± 4.88 mmHg, it decreased to 15.35 ± 3.10 mmHg at 1 year (n = 37) (p = 0.006) and to 14.00 ± 3.78 at 3 years (n = 8) (p = 0.074). Mean number of glaucoma medication requirements decreased from 2.02 ± 1.0 preoperatively to 1.02 ± 0.96 at 1 year (n = 37) (p < 0.001) and to 1.63 ± 0.92 at 3 years (n = 8) (p = 0.197). Complete success was achieved in 17.7% of eyes and qualified success in 54.8%. Two eyes of 2 patients had early postoperative hyphema. Two eyes of 1 patient underwent filtering surgery 2 months after the procedure, and 2 eyes of 1 patient underwent laser trabeculoplasty 3.8 years after the procedure due to uncontrolled IOP. CONCLUSIONS: Combined phacoemulsification and ELT is effective and safe in eyes with mild glaucoma or OHT and cataract. It significantly reduced IOP and glaucoma medication requirements 1 year after surgery.

Complications Occurring Through 5 Years Following Primary Intraocular Lens Implantation for Pediatric Cataract.

Importance: Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective: To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants: This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures: Lensectomy with primary IOL implantation. Main Outcome and Measures: Five-year cumulative incidence of complications by age at surgery (<2 years, 2 to <4 years, 4 to <7 years, and 7 to <13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results: The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P < .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (<2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to <4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to <7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance: In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.

A Comparison of Ocular Complications after 0.7 mg Dexamethasone Implant versus 2 mg of Intravitreal Triamcinolone in Vitrectomized Eyes.

OBJECTIVE: To compare the rates of complications in eyes that received a dexamethasone (DEX) implant (0.7 mg) or intravitreal triamcinolone (IVT) (2 mg) to treat postvitrectomy macular edema (ME). DESIGN: Retrospective, comparative, case series. SUBJECTS: A total of 148 eyes (147 patients); 75 eyes (75 patients) in the DEX group and 73 eyes (72 patients) in the IVT group. METHODS: The medical records of patients who received an intravitreal DEX 0.7 mg (Ozurdex) or triamcinolone (2 mg) (Triesence) for postvitrectomy ME between July 2014 and December 2021 with a minimum follow-up of 3 months were reviewed. Ocular hypotony and ocular hypertension were defined as intraocular pressure of < 6 mmHg and > 24 mmHg, respectively. MAIN OUTCOME MEASURES: The rates of complications. RESULTS: The follow-up duration was 2.5 ± 1.6 years, with no significant difference between the groups (P = 0.398). The rate of transient ocular hypotony per eye and per injection was significantly higher in the DEX group (10 eyes [13%], 30 of 443 injections [7%]) compared with the IVT group (2 eyes [3%], 2 of 262 injections [0.8%]) (P = 0.039 and < 0.001, respectively). Mean visual acuity significantly decreased at the time of ocular hypotony (P = 0.031), but returned to preinjection level after resolution of the hypotony after a median of 12 days. The incidence of ocular hypertension was higher in the DEX group (23 eyes [31%]) than the IVT group (16 eyes [22%]), but this was not statistically significant (P = 0.307). Ocular hypertension was controlled with observation or topical medication. There were no between-group differences in the incidence of vitreous hemorrhage (DEX, 3 eyes [4%]; IVT, 1 eye [1%]; P = 0.632) or rhegmatogenous retinal detachment (DEX, 3 eyes [4%]; IVT, 0 eyes [0%]; P = 0.253). Four eyes (5%) experienced migration of the DEX implant into the anterior chamber. No eye developed endophthalmitis. CONCLUSION: The incidence of ocular hypotony, which causes transient visual impairment, was significantly higher in vitrectomized eyes treated with DEX compared with eyes treated with IVT. Injections other than the inferotemporal quadrant or rotating injection sites may be recommended. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Oral administration of a dual ETA/ETB receptor antagonist promotes neuroprotection in a rodent model of glaucoma.

Purpose: Glaucoma is a neurodegenerative disease associated with elevated intraocular pressure and characterized by optic nerve axonal degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The endothelin (ET) system of vasoactive peptides (ET-1, ET-2, ET-3) and their G-protein coupled receptors (ETA and ETB receptors) have been shown to contribute to the pathophysiology of glaucoma. The purpose of this study was to determine whether administration of the endothelin receptor antagonist macitentan was neuroprotective to RGCs and optic nerve axons when administered after the onset of intraocular pressure (IOP) elevation in ocular hypertensive rats. Methods: Male and female Brown Norway rats were subjected to the Morrison model of ocular hypertension by injection of hypertonic saline through the episcleral veins. Following IOP elevation, macitentan (5 mg/kg body wt) was administered orally 3 days per week, and rats with IOP elevation were maintained for 4 weeks. RGC function was determined by pattern electroretinography (PERG) at 2 and 4 weeks post-IOP elevation. Rats were euthanized by approved humane methods, and retinal flat mounts were generated and immunostained for the RGC-selective marker Brn3a. PPD-stained optic nerve sections were imaged by confocal microscopy. RGC and axon counts were conducted in a masked manner and compared between the treatment groups. Results: Significant protection against loss of RGCs and optic nerve axons was found following oral administration of macitentan in rats with elevated IOP. In addition, a protective trend for RGC function, as measured by pattern ERG analysis, was evident following macitentan treatment. Conclusions: Macitentan treatment had a neuroprotective effect on RGCs and their axons, independent of its IOP-lowering effect, suggesting that macitentan may complement existing treatments to prevent neurodegeneration during ocular hypertension. The findings presented have implications for the use of macitentan as an oral formulation to promote neuroprotection in glaucoma patients.

Increased Risk of Ocular Hypertension in Patients With Cushing's Disease.

PRCIS: An increased risk of ocular hypertension was seen in Cushing's disease. INTRODUCTION: Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown. MATERIALS AND METHODS: The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP. RESULTS: A total of 52 patients (38.4±12.4 y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4 mm Hg and right 20.0±7.1 mm Hg) than in patients with acromegaly (left 17.5±2.3 mm Hg and right 18.6±7.0 mm Hg, P =0.033) and patients with NFPA (left 17.8±2.6 mm Hg and right 17.4±2.4 mm Hg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery. CONCLUSIONS: An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.

Optic Disc Drusen in Patients With Ocular Hypertension: A Case Series and Review of the Literature.

BACKGROUND: The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form of intraocular pressure (IOP) reduction is controversial. Here, we present a series of patients with coexisting ocular hypertension and ODD to evaluate clinical features, treatment options, and progression of optic neuropathy. In addition, a review of the literature on ODD with elevated IOP is provided. METHODS: Six patients with ODD and a history of ocular hypertension are presented. Components of the examination and imaging modalities used to establish the diagnosis of ODD were recorded and a description of ocular hypertension history, glaucoma testing, and the potential treatment of IOP were also provided. RESULTS: In this series, 4 of 6 patients with concurrent ocular hypertension and ODD showed progression of optic neuropathy as assessed by visual field or retinal nerve fiber layer thickness. Of the 2 patients who did not show evidence of progression, 1 was treated with IOP-lowering medications and 1 was observed off treatment. Of the 4 patients who showed evidence of progression, all 4 were initially treated with IOP-lowering medications and 2 ultimately went on to have trabeculectomy surgery. In the patients with progressive optic neuropathy, lowering the IOP seemed to halt the progression suggesting there was a pressure-sensitive component. CONCLUSIONS: Distinguishing changes to the optic nerve, particularly the structural changes at the lamina cribrosa of true glaucomatous optic neuropathy in the setting of ODD, is a challenge. Careful consideration of risk factors including age, presenting features, progression indicators, and management goals is to be accounted for in the decision to offer treatment. We see the presence ODD in the patients with ocular hypertension as an additional risk for progressive changes to the nerve fiber layer and visual field that needs to be considered when determining whether to initiate therapy. Our data suggest that treatment of IOP in the patients with ocular hypertension with ODD and evidence of progression reduces the risk of further progression. Further work is needed to determine whether progression of optic neuropathy in the setting of coexisting ODD and ocular hypertension is related mechanistically to predominantly an ODD-type process, a glaucomatous process, or a combination thereof.

Pro-inflammatory cytokines in aqueous humor from dogs with anterior uveitis and post-operative ocular hypertension following phacoemulsification, primary glaucoma, and normal healthy eyes.

BACKGROUND: The aim of this study was to evaluate the levels of pro-inflammatory cytokines in aqueous humor (AH) from dogs with anterior uveitis and post-operative ocular hypertension (POH) following phacoemulsification, in AH from dogs with primary glaucoma, and in normal healthy eyes with no signs of anterior uveitis or other ocular diseases. METHODS: An exploratory study including 21 samples of AH collected from 15 dogs; post-phacoemulsification with anterior uveitis and POH ('POH group', n = 10 samples), primary glaucoma ('glaucoma group', n = 6 samples), and normal ('normal group', n = 5 samples). Target mass spectrometry via multiple reaction monitoring (MRM-MS) with the Canine Cytokine SpikeMix™ as internal standard was used to measure the pro-inflammatory cytokine levels. RESULTS: The MRM-MS method measured 15 pro-inflammatory cytokines. Tumor-necrosis-factor-alpha (TNFα) and interleukin-18 (IL-18) levels in AH were different between all three groups (glaucoma>POH>normal) (p = .05, p = .02, respectively). Additionally, IL-6 was higher in the 'POH group' compared to the 'glaucoma group' (p = .04) and IL-4 was higher in the 'POH group' compared to the 'normal group' (p = .04). Intraocular pressure (IOP) was positively associated with increased AH levels of IL-18 (Spearman correlation = .64, p = .03). CONCLUSIONS: MRM-MS using the Canine Cytokine SpikeMix™ as an internal standard was established as a method to detect pro-inflammatory cytokine levels in canine AH. The study demonstrated increased levels of IL-4, IL-6, IL-18, and TNFα in AH from canines with POH following phacoemulsification. Primary glaucomatous eyes had the highest levels of IL-18 and TNFα which may indicate that inflammation plays a role in the pathogenesis of primary glaucoma in dogs.

Urrets-Zavalia syndrome following cataract surgery in dogs: A case series.

Background: In human medicine, Urrets-Zavalia syndrome (UZS) is a well-recognized but uncommon postoperative complication characterized by a fixed dilated pupil, accompanied by iris atrophy and glaucoma. Although it was originally reported in 1963 after penetrating keratoplasty surgery for keratoconus, it has been associated with various ophthalmic procedures such as cataract surgery. The condition has not been previously published in the veterinary literature. Case Description: Three client-owned diabetic dogs that developed UZS´s triad after cataract surgery are described. Despite uneventful phacoemulsification in the six eyes, five developed moderate-to-severe postoperative ocular hypertension. Although intraocular pressure (IOP) spikes were initially controlled, fixed dilated pupils accompanied by iris atrophy and chronic ocular hypertension were seen in the five affected eyes. Aggressive medical and surgical management maintained vision in three of those eyes. In one eye, uncontrolled IOP led to blindness. Conclusion: This is the first published description of UZS in dogs, occurring after phacoemulsification. Although no exact, demonstrable causative element could be determined, we believe that should be considered a triggering condition for this syndrome, as it directly affects the ocular blood flow autoregulation and intrinsic uveal tissue integrity. Until the contrary is proved, diabetes mellitus might be considered as a risk factor for developing this syndrome after cataract surgery in dogs.

Review of de novo uveitis in older adults presenting to a large tertiary centre.

BACKGROUND/AIMS: The primary aim of this study was to describe the causes of de novo uveitis in individuals 60 years and older. Secondary objectives were to determine the incidence of intraocular lymphoma and the clinical predictors of lymphoma. METHODS: Retrospective chart review of all subjects presenting to the uveitis service at Auckland District Health Board (Auckland, New Zealand) between January 2006 and October 2020 RESULTS: 686 subjects (900 eyes) were aged ≥60 years at first presentation with uveitis, representing 23.4% of all subjects with uveitis during the study period. Non-infectious aetiology occurred in 631 (70.1%) eyes and infectious etiologies occurred in 269 (29.9%) eyes. The most frequent causes were idiopathic (36.3%), herpes zoster (14.8%), HLAB27 (8.7%) and sarcoidosis (4.8%). Twenty (2.2%) eyes of 13 (1.9%) subjects had a diagnosis of lymphoma. Lymphoma represented 11.2% of all intermediate uveitis. Subjects diagnosed with lymphoma did not develop posterior synechiae, epiretinal membrane, cystoid macular oedema or ocular hypertension. CONCLUSIONS: Intraocular lymphoma was uncommon in the overall cohort, but an important cause of intermediate uveitis. A diagnosis of lymphoma needs to be considered in any older subject with de novo intermediate uveitis. The lack of posterior synechiae, cystoid macular oedema, epiretinal membrane and ocular hypertension further increases the suspicion for lymphoma.

High rate of conversion from ocular hypertension to glaucoma in subjects with uveitis.

AIMS: To examine presentation, management and long-term sequelae of ocular hypertension and uveitic glaucoma. METHODS: Retrospective observational study of all subjects with uveitic glaucoma or ocular hypertension seen in Auckland uveitis clinics over the last 10 years. RESULTS: A total of 188 eyes of 139 subjects with uveitic glaucoma or ocular hypertension were included for analysis. Total follow-up was 1854.5 eye years (mean 9.9 years). The mean age at uveitis diagnosis was 49.3 years. 52.5% of subjects were male. The most common diagnoses were idiopathic uveitis (29.3%), sarcoidosis (13.3%), herpes zoster (6.9%), HLA-B27 uveitis (6.9%), tuberculosis (5.9%) and Posner-Schlossmann or cytomegalovirus (CMV) uveitis (5.3%). Median intraocular pressure (IOP) at diagnosis was 35 mm Hg (IQR 29-45). 144 eyes (77.0%) developed glaucoma during the follow-up period, of whom 41 lost some central vision due to glaucoma. Oral acetazolamide was required for IOP control in 64.5%, 50 eyes underwent trabeculectomy, 18 eyes required a tube and 6 underwent minimally invasive glaucoma surgery. CONCLUSION: Rapid progression was observed from ocular hypertension to uveitic glaucoma. Uveitic glaucoma is aggressive, with high likelihood of requiring surgical management and high risk of central vision loss. Close collaboration between uveitis and glaucoma specialists is required to maximise outcomes for these patients.

Cataract extraction and intraocular pressure-lowering agents delivery: A nationwide French study between 2005 and 2017.

PURPOSE: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. MATERIAL AND METHODS: Longitudinal matched exposed-unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. RESULTS: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (-25.5% vs -3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication (p < 0.0001). CONCLUSIONS: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.

Cataract Surgery Lowers Intraocular Pressure and Medication Use in the Medication Group of the Ocular Hypertension Treatment Study.

PURPOSE: To determine the change in intraocular pressure (IOP) and ocular hypotensive medication use after cataract extraction in the Medication Group of the Ocular Hypertension Treatment Study. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: We included 92 participants (n = 149 eyes) of the Medication Group of the Ocular Hypertension Treatment Study who underwent cataract surgery in at least 1 eye during the study and 531 participants (n = 1004 eyes) of the Medication Group who did not undergo cataract surgery. We defined the "split date" as the first study visit that cataract surgery was reported for the cataract surgery group and the 15th visit in the control group to equalize the median number of visits. We then compared the 2 groups at visits relative to this split date. MAIN OUTCOME MEASURES: Difference in preoperative and postoperative IOP, and number of classes of ocular hypotensive medications between the cataract and control group over a 72-month period. RESULTS: Cataract surgery significantly decreased the number of ocular hypotensive medications at all postoperative visits (mean, -0.4 medications; P ≤ .005) through the 48-month postoperative visit when compared with the control group. At the split date, approximately 23% of eyes were medication free and 41% had a reduced medication burden. Cataract surgery resulted in a decrease in IOP (P < .001), but the difference in IOP between the groups reduced over time and became nonsignificant after 12 months. CONCLUSIONS: Cataract surgery in patients with ocular hypertension produced sustained reductions in the average number of ocular hypotensive medications and transient reductions in IOP.

Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma.

BACKGROUND: Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. METHODS: A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. RESULTS: We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. CONCLUSIONS: These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.

Uveítis asociada a la artritis idiopática juvenil / Uveitis associated to juvenile idiopathic arthritis

Objetivo: Caracterizar las uveítis asociadas a la artritis idiopática juvenil. Métodos: Se realizó un estudio observacional, descriptivo, de corte transversal, donde se evaluaron las variables edad, raza, sexo, lateralidad de la uveítis, clasificación anatómica, agudeza visual mejor corregida, presencia de complicaciones y tratamiento. Resultados: Predominaron los mayores de seis años, el sexo femenino y la raza blanca. En cuanto a la lateralidad hubo mayor predominio de las bilaterales, con localización anatómica anterior. En los resultados visuales sobresalieron los que presentaban una agudeza visual mejor corregida ≥ 0,5. Las complicaciones más frecuentes fueron: la pérdida visual, la hipertensión ocular y la queratopatía en banda. Con respecto al tratamiento, la mayoría de los pacientes tenían asociado metotrexate al tratamiento tópico y oral con esteroides. Conclusión: La uveítis asociada a la artritis idiopática juvenil sigue siendo un problema importante de salud en la infancia a pesar de los avances en los programas de atención a esta enfermedad; por tanto, el diagnóstico precoz, el seguimiento estricto y el tratamiento adecuado son los pilares para una mejor evolución(AU)

Objective: Characterize uveitis associated to juvenile idiopathic arthritis. Methods: A cross-sectional observational descriptive study was conducted based on evaluation of the following variables: age, race, sex, laterality of uveitis, anatomical classification, best corrected visual acuity, presence of complications and treatment. Results: A predominance was observed of patients aged over six years, female sex and white race. Bilateral uveitis prevailed, with anterior anatomical location. Patients with a best corrected visual acuity ≥ 0.5 stood out for their visual results. The most common complications were visual loss, ocular hypertension and band keratopathy. Most patients had methotrexate associated to topical and oral treatment with steroids. Conclusion: Uveitis associated to juvenile idiopathic arthritis continues to be an important health problem in childhood, despite the progress in the care of this condition. Therefore, early diagnosis, strict follow-up and appropriate treatment are the pillars of a better evolution(AU)

Clinical characteristics and prognostic factors in hypertensive anterior uveitis diagnosed with polymerase chain reaction.

Aim of the study is to report the clinical characteristics and prognostic factors in hypertensive anterior uveitis (AU) diagnosed with multiplex polymerase chain reaction (PCR). Eighty-eight eyes of 88 patients with hypertensive AU were enrolled from 2015 to 2019 in a tertiary center in South Korea. All patients underwent multiplex PCR that was performed using aqueous humor samples collected at first visit to detect the DNA of six herpesviruses. Twenty-eight (31.8%) eyes were PCR positive. Herpes simplex virus was found in 6 (6.8%) eyes, varicella-zoster virus in 7 (8.0%) eyes, cytomegalovirus in 14 (15.9%) eyes, and Epstein-Barr virus in 1 (1.1%) eye. On multivariate regression analysis, PCR positivity was significantly associated with coin-shaped keratic precipitates (odds ratio (OR) = 6.01, P = 0.044). Recurrence and final visual acuity were significantly associated with a presumed diagnosis of viral endotheliitis (OR = 21.69, P = 0.04 and OR = 6.3, P = 0.004, respectively). This study showed the importance of PCR positivity, suggesting that identification of the virus through active PCR testing could affect the course, treatment, and prognosis of hypertensive AU.

GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension.

Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells (RGCs). Recent studies have implicated pro-inflammatory microglia, macrophages, and A1 astrocytes in the pathogenesis of neurodegenerative diseases. The role of pro-inflammatory, neurotoxic A1 astrocytes in glaucoma is just beginning to be explored. Using a mouse model of glaucoma, we demonstrate that ocular hypertension is sufficient to trigger production of C1q, interleukin-1α (IL-1α), and tumor necrosis factor α (TNF-α), three cytokines necessary and sufficient to drive the formation of A1 astrocytes. Upregulation of these cytokines occurs first in CD11b+ CD11c+ cells followed by CD11b+ CD11c- cells. Ablation of this pathway, by either genetic deletions of C1qa, IL-1α, and TNF-α, or treatment with glucagon-like peptide-1 receptor agonist NLY01, reduces A1 astrocyte transformation and RGC death. Together, these results highlight a neuroinflammatory mechanism of glaucomatous neurodegeneration that can be therapeutically targeted by NLY01 administration.

Activation of adenosine A3 receptor protects retinal ganglion cells from degeneration induced by ocular hypertension.

Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness. This disease is characterized by optic nerve damage and retinal ganglion cell (RGC) death. The current treatments available target the lowering of intraocular pressure (IOP), the main risk factor for disease onset and development. However, in some patients, vision loss progresses despite successful IOP control, indicating that new and effective treatments are needed, such as those targeting the neuroprotection of RGCs. Adenosine A3 receptor (A3R) activation confers protection to RGCs following an excitotoxic stimulus. In this work, we investigated whether the activation of A3R could also afford protection to RGCs in the laser-induced ocular hypertension (OHT) model, a well-characterized animal model of glaucoma. The intravitreal injection of 2-Cl-IB-MECA, a selective A3R agonist, abolished the alterations induced by OHT in the negative and positive components of scotopic threshold response (STR) without changing a- and b-wave amplitudes both in scotopic and photopic conditions. Moreover, the treatment of OHT eyes with the A3R agonist promoted the survival of RGCs, attenuated the impairment in retrograde axonal transport, and improved the structure of the optic nerve. Taking into consideration the beneficial effects afforded by 2-Cl-IB-MECA, we can envisage that A3R activation can be considered a good therapeutic strategy to protect RGCs from glaucomatous damage.

Glaucoma in children with facial port wine stain.

PURPOSE: To report on the clinical presentation and surgical treatment (procedure and outcome(s)) of glaucoma in children with facial port wine stain. MATERIALS AND METHODS: This is a retrospective chart review of children with facial port wine stain referred to Alexandria University paediatric ophthalmology practice from 2005 to 2016. The charts of 22 children (44 eyes) with facial port wine stain were reviewed. The data extracted included demographics, results of ophthalmic examination findings and treatment(s). The main outcome measures were the number of eyes stratified as glaucoma, glaucoma suspects and no glaucoma at the initial and final presentations. RESULTS: The average age of presentation was 18.2 (±33.9) months. After a follow-up of over 16.1 (±24.8) months, there were 34%, 30% and 36% of the study eyes diagnosed as glaucoma, glaucoma suspects and no glaucoma, respectively with mean ± standard deviation of intraocular pressure of 20.6 ± 5.1, 13.6 ± 5.4 and 7.5 ± 1.7 mmHg. The majority (91%) of eyes presenting with glaucoma had clear corneas. In total, 11 eyes were operated upon for glaucoma. The recorded success rate was 91%. Two eyes developed a postoperative exudative choroidal detachment, of which one resolved spontaneously and the other was successfully managed by intravitreal gas injection. CONCLUSION: Glaucoma is a significant ocular hazard in children with facial port wine stain that may not be evident on the initial presentation. The presentation is usually with a clear cornea and surgical intervention is associated with a high success rate and a low rate of complications.