Surgical Outcomes in Uveitic Glaucoma: Long-Term Evaluation of Trabeculectomy, Non-Penetrating Deep Sclerectomy, Ex-PRESS Shunt and Ahmed Glaucoma Valve. A 3-Year Follow-Up Study.

PURPOSE: Uveitis can lead to secondary glaucoma, a condition with challenging management that can carry irreversible visual loss. Filtering surgery has demonstrated a higher failure rate, increased incidence of postoperative complications and reinterventions in uveitic patients. There is no consensus on the optimal surgical approach for uveitic glaucoma (UG) due to limited data comparing various intraocular pressure (IOP)-lowering surgeries. This retrospective cohort aims to assess the clinical outcomes of trabeculectomy (TBT), non-penetrating deep sclerectomy (NPDS), Ex-PRESS shunt and Ahmed glaucoma valve, providing additional insights into the long-term IOP control and safety of filtering surgeries in UG. METHODS: The filtering surgery was performed on 32 eyes of 27 UG patients. Complete success was defined as IOP ≤ 18 mmHg or a 30% reduction. Qualified success allowed topical hypotensive treatment. RESULTS: Complete success was 40.63% (13/32) at 12 months and 36.67% (11/30) at 36 months. Qualified success was 84.38% (27/32) at 12 months and 63.33% (19/30) at 36 months. In the survival analysis, both NPDS and Ex-PRESS demonstrated decreased failure rates compared to TBT (NPDS vs TBT: HR = 0.20, p = 0.049; Ex-PRESS vs TBT: HR = 0.28, p = 0.13). One or more reinterventions were required in 34.38% (11/32) of the eyes. NPDS had the lowest incidence of hypotony. Secondary cataract was a common complication in all groups. CONCLUSION: Various filtering surgeries are safe and effective procedures for lowering IOP and reducing the requirement of topical antihypertensives in UG at 36 months. However, one-third of the patients will require another IOP-lowering procedure.

Author Correction: The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Possible Intraluminal Obstruction of the XEN45 Gel Stent Observed With Anterior Segment Optical Coherence Tomography.

PURPOSE: We herein describe possible intraluminal obstruction because of a hyperreflective material found in anterior segment optical coherence tomography (AS-OCT) in 16 of 46 cases with XEN45 gel stent. MATERIALS AND METHODS: This is a retrospective case series of 46 eyes of 39 patients with noncomplicated XEN45 gel stent surgery, analyzed with AS-OCT and slit-lamp photography after at least 6 postoperative months. RESULTS: Possible luminal obstruction in the subconjunctival segment of the implant was observed in 16 eyes of 15 patients, characterized by hyperreflective material on AS-OCT, which was not visible in slit-lamp photography. This was found in 15 eyes following combined procedures and in 1 eye following XEN45 alone. None showed signs of filtering bleb on AS-OCT or slit-lamp photography. In 1 case, the discontinuity between the hyperreflective material and subconjunctival opening of the implant tube was evidenced, and in another case, a focal deposit in the intracameral end of the implant was seen. CONCLUSIONS: We have successfully described the lumen implant deposit of material as a possible cause of late failure of the implant. AS-OCT allows the identification of such cases and may be useful to plan further postoperative interventions for better patient outcomes.

The LRRC8-mediated volume-regulated anion channel is altered in glaucoma.

Regulation of cellular volume is an essential process to balance volume changes during cell proliferation and migration or when intracellular osmolality increases due to transepithelial transport. We previously characterized the key role of volume-regulated anion channels (VRAC) in the modulation of the volume of trabecular meshwork (TM) cells and, in turn, the aqueous humour (AH) outflow from the eye. The balance between the secretion and the drainage of AH determines the intraocular pressure (IOP) that is the major casual risk factor for glaucoma. Glaucoma is an ocular disease that causes irreversible blindness due to the degeneration of retinal ganglion cells. The recent identification of Leucine-Rich Repeat-Containing 8 (LRRC8A-E) proteins as the molecular components of VRAC opens the field to elucidate their function in the physiology of TM and glaucoma. Human TM cells derived from non-glaucomatous donors and from open-angle glaucoma patients were used to determine the expression and the functional activity of LRRC8-mediated channels. Expression levels of LRRC8A-E subunits were decreased in HTM glaucomatous cells compared to normotensive HTM cells. Consequently, the activity of VRAC currents and volume regulation of TM cells were significantly affected. Impaired cell volume regulation will likely contribute to altered aqueous outflow and intraocular pressure.

The EX-PRESS glaucoma shunt versus nonpenetrating deep sclerectomy with Esnoper implant in combined surgery for open-angle glaucoma: a prospective randomized study.

PURPOSE: To report 1-year treatment outcomes of P50 EX-PRESS implant versus nonpenetrating deep sclerectomy (NPDS) with Esnoper V2000 combined with phacoemulsification. DESIGN: Randomized, prospective and multicentre clinical trial. METHODS: Settings: Six clinical centres. POPULATION: Patients 54-89 years of age without previous filtering surgery with cataract and glaucoma who required lower levels of intraocular pressure (IOP). INTERVENTIONS: Phaco-EX-PRESS P50 or Phaco-NPDS with Esnoper V2000, both groups with mitomycin C (0.2 mg/ml for 2 min). MAIN OUTCOME MEASURES: IOP, complete success rate (IOP: ≥6 and ≤18 mmHg), visual acuity, use of medical therapy and systematic assessment of complications and postoperative interventions. RESULTS: A total of 98 eyes were enrolled, including 50 in the EX-PRESS group and 48 in the NPDS group. At 12 months, IOP (mean ± SD) was 13.9 ± 3.3 mmHg in EX-PRESS group and 13.3 ± 3.6 mmHg in NPDS group (p = 0.38). Success rate was 75% and 80% in EX-PRESS and NPDS groups, respectively (p = 0.53). The number of glaucoma medications (mean ± SD) was 0.2 ± 0.55 in EX-PRESS group and 0.17 ± 0.44 in NPDS group (p = 1.00). The total number of complications was 66 in 35 subjects in EX-PRESS group and 39 in 23 subjects in NPDS group (p = 0.02). The incidence of more than one complication was n = 13 (26%) versus n = 9 (18.8%) in EX-PRESS and NPDS groups, respectively (p = 0.38). The total number of required postoperative interventions was 59 and 26 in EX-PRESS and NPDS groups, respectively (p = 0.01). Visual acuity was similar in both groups at month 12 (p = 0.13). Surgical time (mean ± SD) was 52.6 ± 13.6 min in EX-PRESS group and 63.3 ± 19.4 min in NPDS group (p = 0.01). CONCLUSION: Phaco-EX-PRESS surgery had similar success rate compared to Phaco-NPDS during 1 year of follow-up. Both procedures were associated with similar IOP reduction and use of additional medical therapy at 12 months. EX-PRESS surgery required more postoperative interventions and had more complications, but needed less surgical time compared to NPDS.

Acid-sensing ion channels detect moderate acidifications to induce ocular pain.

Sensory nerve fibers innervating the ocular anterior surface detect external stimuli producing innocuous and painful sensations. Protons are among the first mediators released by damaged cells during inflammation, tissue injury, or other chronic ophthalmic conditions. We studied whether acid-sensing ion channels (ASICs) are expressed in corneal sensory neurons and their roles in the response to moderate acidifications of the ocular surface and in pathologies producing ocular surface inflammation. Moderate acidic pH (6.6) activated ASIC-like currents in corneal sensory neurons, which were blocked by ASIC1- or ASIC3-specific toxins. Acidic pH depolarizes corneal sensory neurons to fire action potentials, an effect blocked by the ASIC3 inhibitor APETx2. 2-Guanidino-4-methylquinazoline, an ASIC3 agonist, activated a population of corneal polymodal sensory nerve fibers and significantly increased the blinking and tearing rate. The nocifensive behaviors produced by application of either a moderate acidic stimulus or ophthalmic drugs formulated in acidic solution were abolished by ASIC blockers. In a model of allergic keratoconjunctivitis, nocifensive behavior was greatly reduced by ASIC3 blockade, presumably by reducing nociceptor sensitization during the inflammatory process. Our results show that, in addition to the established role of TRPV1, ASICs play a significant role in the detection of acidic insults at the ocular surface. The identification of ASICs in corneal neurons and their alterations during different diseases is critical for the understanding of sensory ocular pathophysiology. They are likely to mediate some of the discomfort sensations accompanying several ophthalmic formulations and may represent novel targets for the development of new therapeutics for ocular pathologies.

Glaucoma progression detection: agreement, sensitivity, and specificity of expert visual field evaluation, event analysis, and trend analysis.

PURPOSE: To assess sensitivity, specificity, and agreement among automated event analysis, automated trend analysis, and expert evaluation to detect glaucoma progression. METHODS: This was a prospective study that included 37 eyes with a follow-up of 36 months. All had glaucomatous disks and fields and performed reliable visual fields every 6 months. Each series of fields was assessed with 3 different methods: subjective assessment by 2 independent teams of glaucoma experts, glaucoma/guided progression analysis (GPA) event analysis, and GPA (visual field index-based) trend analysis. Kappa agreement coefficient between methods and sensitivity and specificity for each method using expert opinion as gold standard were calculated. RESULTS: The incidence of glaucoma progression was 16% to 18% in 3 years but only 3 cases showed progression with all 3 methods. Kappa agreement coefficient was high (k=0.82) between subjective expert assessment and GPA event analysis, and only moderate between these two and GPA trend analysis (k=0.57). Sensitivity and specificity for GPA event and GPA trend analysis were 71% and 96%, and 57% and 93%, respectively. CONCLUSIONS: The 3 methods detected similar numbers of progressing cases. The GPA event analysis and expert subjective assessment showed high agreement between them and moderate agreement with GPA trend analysis. In a period of 3 years, both methods of GPA analysis offered high specificity, event analysis showed 83% sensitivity, and trend analysis had a 66% sensitivity.

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker.

Reproducibility of measurements and variability of the classification algorithm of Stratus OCT in normal, hypertensive, and glaucomatous patients.

PURPOSE: To assess the reproducibility of retinal nerve fiber layer (RNFL) measurements and the variability of the probabilistic classification algorithm in normal, hypertensive and glaucomatous eyes using Stratus optical coherence tomography (OCT). METHODS: Forty-nine eyes (13 normal, 17 ocular hypertensive [OHT] and 19 glaucomatous) of 49 subjects were included in this study. RNFL was determined with Stratus OCT using the standard protocol RNFL thickness 3.4. Three different images of each eye were taken consecutively during the same session. To evaluate OCT reproducibility, coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated for average thickness (AvgT), superior average thickness (Savg), and inferior average thickness (Iavg) parameters. The variability of the results of the probabilistic classification algorithm, based on the OCT normative database, was also analyzed. The percentage of eyes with changes in the category assigned was calculated for each group. RESULTS: The 50th percentile of COV was 2.96%, 4.00%, and 4.31% for AvgT, Savg, and Iavg, respectively. Glaucoma group presented the largest COV for all three parameters (3.87%, 5.55%, 7.82%). ICC were greater than 0.75 for almost all measures (except from the inferior thickness parameter in the normal group; ICC = 0.64, 95% CI 0.334-0.857). Regarding the probabilistic classification algorithm for the three parameters (AvgT, Savg, Iavg), the percentage of eyes without color-code category changes among the three images was as follows: normal group, 100%, 84.6% and 92%; OHT group, 89.5%, 52.7%, 79%; and Glaucoma group, 82%, 70.6%, and 76.5%, respectively. A probabilistic category switch from pathologic to normal or vice versa was observed in three eyes (15.8%) of the glaucomatous group for the Savg parameter and in two eyes of the OHT group: one eye (5,9%) for the AvgT and one eye (5.9%) for the Savg parameter. CONCLUSIONS: OCT RNFL measurements showed a good reproducibility in normal, OHT, and glaucoma eyes. The probabilistic classification for the three main parameters showed certain variability, especially in glaucoma group and OHT group. Therefore, one isolated category result should be interpreted with caution before clinical classification of the patient.