XEN-45 in the management of early glaucoma surgery: A national Delphi consensus study.

BACKGROUND AND OBJECTIVE: Recommendations on general glaucoma management and the use of early minimally invasive and microincisional surgeries are limited. This study aimed to establish consensus regarding glaucoma management, focusing on the XEN-45 gel stent implant. METHODS: A Delphi consensus-driven process was used. The scientific committee led the study, identified the expert panel, and participated in elaborating the questionnaire. Fifty-one panelists were invited to complete, on a nine-point Likert scale, an 89-item questionnaire covering three topic blocks. Two Delphi rounds were performed. Consensus was achieved if ≥66.6% of panelists reached agreement or disagreement. RESULTS: Panelists agreed on 84 items related to the patients' quality of life, the therapeutic algorithm and patient profile, and surgical and pre- and post-operative management. Panelists agreed on the suitability of XEN stent implants to treat glaucoma at different stages and for different patient profiles: young patients, elderly or with significant comorbidities, and with myopic glaucoma, patients who failed previous surgeries, and with previous poor post-operative experience. XEN surgery was considered a therapeutic step prior to classic filtering surgery and a possible first surgical option in elderly patients with comorbidities and uncontrolled intraocular pressure. XEN surgery allows the patient to return to routine daily activities faster than conventional filtering surgeries and to reduce and/or eliminate topical treatments. CONCLUSIONS: This Delphi-driven consensus resulted in a series of general recommendations for glaucoma management, including those related to patient quality of life, therapeutic algorithm, and patient profile, and specific ones regarding the use of XEN stent gel surgery.

Detection and characterisation of visual field defects using Octopus perimetry in congenital glaucoma.

PURPOSE: To detect and characterise visual field (VF) defects using static Octopus perimetry in patients with primary congenital glaucoma (PCG) and to determine VF quality and time duration. MATERIAL AND METHODS: Eighty-eight eyes of 70 patients diagnosed with PCG were included. Assessments were performed using an Octopus 900 and each eye was assessed with the tendency-oriented perimetry (G-TOP) algorithm. Quantitative VF data were collected: quality data (false positive and negative response, and time duration) and results of mean deviation (MD) and square root of loss variance (sLV). Qualitative data were collected: the presence of diffuse and localized defects, the affected hemifield and grade of defects using the Aulhorn and Karmeyer classification. Correlations between perimetric results and clinical variables were analysed. RESULTS: Median age was 11 (8-17) years. 65.9% (58/88) of PCG eyes showed VF defects. Diffuse defects were observed in 10/58 eyes (16.94%) (mean MD = 23.92 [SD: 2.52]) dB) and localized defects in 48/58 eyes (82.75%). The most frequent defect was spot-like/stroke-like/incipient paracentral scotoma (n = 15), nasal step (n = 8), adding arcuate defect (n = 2), half ring-shaped (n = 13) and concentric defect with a central island (n = 9). And the most frequent affected visual hemifield was inferior hemifield. Mean test duration was 2 min 12 s (SD: 21.6 s). MD and sLV values were correlated with best corrected visual acuity (BCVA), cup to disc ratio and number of antiglaucoma surgeries (all P < .001). CONCLUSION: A high number of diffuse and localized defects were identified using Octopus perimetry in PCG patients. The most frequent defect was paracentral scotoma and inferior hemifield was the most affected.

Diagnostic ability of vessel density of the optic nerve head and macula versus structural parameters with optical coherence tomography in pseudoexfoliative glaucoma.

PURPOSE: To evaluate the diagnostic ability of the vessel density (VD) of the optic nerve head (ONH) and the macula on optical coherence tomography (OCT) angiography and the retinal nerve layer thickness (RNFL) thickness and the macular ganglion cell complex (GCC) thickness on OCT in patients with pseudoexfoliative glaucoma (PXG). METHODS: Cross-sectional study including PXG patients and healthy controls. Demographic and clinical data were noted for all participants. Optical coherence tomography (OCT) and OCT angiography (OCTA) images of the ONH and macular area were obtained with the RS-3000 Advance OCT (Nidek Co., Gamagori, Japan). The RNFL and GCC thickness of different sectors was provided by the software. Macular VD of the superficial capillary plexus (SCP) and ONH VD of the radial peripapillary capillary plexus (RPCP) were registered. Groups were compared and area under the receiver operating characteristic (AUROC) curves were used to determine the power of discrimination of each parameter. RESULTS: RNFL and GCC thickness and ONH and macular VD were significantly lower in PXG patients compared with healthy controls (all, p<0.05). The best discrimination parameter was the average RNFL thickness (AUROC: 0.928). ONH VD AUROC was better than that of macular VD (AUROC: 0.897 and 0.780, respectively). ONH VD AUROC was comparable to RNFL thickness (p<0.001). CONCLUSIONS: The diagnostic ability of ONH vessel density in PXG appears comparable to that of the structural parameters, RNFL and GCC thickness, obtained with OCT, and may be a valuable tool in clinical practice.

Reproducibility of peripapillary, optic nerve head and macular vessel density by OCT-A according to glaucoma severity staging.

OBJECTIVE: To assess the reproducibility of peripapillary, optic nerve head (PP-ONH) and macular vessel density (VD) by Spectral Domain optical coherence tomography angiography (SD OCT-A) in glaucoma patients and healthy subjects. METHODS: Cross-sectional study assessing 63 eyes of 63 subjects, including 33 glaucoma patients and 30 healthy subjects. Glaucoma was classified in mild, moderate, or advanced. Two consecutive scans were acquired by Spectralis Module OCT-A (Heidelberg, Germany), and provided images of the superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP); deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). VD (%) was calculated by AngioTool. Intraclass correlation coefficients (ICCs) and coefficients of variation (CV) were calculated. RESULTS: Among PP-ONH VD, better ICC presented advanced (ICC 0.86-0.96) and moderate glaucoma (ICC 0.83-0.97) compared with mild glaucoma (0.64-0.86). For the macular VD reproducibility, ICC results for superficial retinal layers were better for mild glaucoma (0.94-0.96) followed by moderated (0.88-0.93) and advanced glaucoma (0.85-0.91), and for deeper retinal layers ICC was better for moderate glaucoma (0.95-0.96) followed by advanced (0.80-0.86) and mild glaucoma (0.74-0.91). CVs ranged from 2.2% to 10.94%. Among healthy subjects, ICCs for the PP-ONH VD measurements (0.91-0.99) and for the macular VD measurements (0.93-0.97) were excellent in all layers, with CVs from 1.65% to 10.33%. CONCLUSIONS: SD OCT-A used to quantify macular and PP-ONH VD showed excellent and good reproducibility in most layers of the retina, both in healthy subjects and in glaucoma patients regardless of the severity of the disease.

Dependence of corneal hysteresis on non-central corneal thickness in healthy subjects.

OBJECTIVE: To evaluate the dependence of corneal hysteresis (CH) on non-central corneal thickness. METHODS: Cross-sectional study of 1561 eyes of 1561 healthy volunteers with IOP less than 21mmHg, open angles on gonioscopy and no prior eye surgeries or local or systemic diseases. Pentacam-Scheimpflug technology was employed to segment the cornea into 6 circular zones centered on the apex (zones 1-6) and to determine the mean corneal thickness of these areas. CH was measured with ORA. Univariate and multivariate linear regression models adjusted for age and sex were created to model the dependence of CH on corneal thickness in zones 1 to 6. RESULTS: In the univariate linear regression models, we found that CH was dependent on mean corneal thickness of zone 1 (B=0,004; R2=0.95%; P<0.001), zone 2 (B=0,004; R2=0.57%; P=0.002), zone 4 (B=0,005; R2=1.50%; P<0.001) and zone 6 (B=0,003; R2=0.92%; P<0.001). Similar results were obtained in the multivariate model (R2=3.46%; P<0.001). CONCLUSION: This study suggests a significant dependence of CH on non-central corneal thickness. The model of corneal thickness segmentation into circular zones centered on the corneal apex is able to explain 3.47% of the variation in CH measurements.

Analysis of the influence of corneal properties and densitometry on applanation and rebound tonometry in primary open angle glaucoma.

PURPOSE: To evaluate the influence of corneal densitometry on portable applanation (Perkins) and rebound (iCare ic100 and PRO) tonometry. A secondary goal was to assess if there was a relationship between various corneal properties and the severity of primary open angle glaucoma (POAG). MATERIAL AND METHODS: Seventy-five eyes of 75 patients with primary open angle glaucoma were studied, divided by severity into 3 groups: 25 mild, 25 moderate and 25 advanced. Intraocular pressure (IOP) was measured 3 times in each participant with a Perkins applanation tonometer (PAT), a handheld version of the Goldman applanation tonometer (GAT), an iCare PRO and an iCare ic100. Mean values were then calculated. Corneal topography with the Pentacam HR (Oculus, Wetzlar, Germany) was also performed in all individuals. RESULTS: Mean age and sex were comparable in all groups, as were densitometry values (P>0.05). The mean visual field defect (MD) was 2.85 (±1.23) dB in the mild glaucoma group, 8.26 (±1.90) dB in the moderate group and 15.66 (±3.46) dB in the advanced group. Three multivariate regression analyses were performed. The first and second calculations assessed the effect of IOP obtained with iCare ic100 and PAT as dependent variables with age, sex, CCT and mean keratometry (Km) within the glaucoma subgroups and the global sample. The third analysis was carried out to assess the relationship between corneal densitometry as the dependant variable and the aforementioned corneal parameters among the glaucoma groups. In the first multivariate regression analysis, a statistically significant correlation was found between ic100 rebound tonometry and CCT in the POAG global sample (coef. 0.117; IC [-0.21-(-0.01)]; P=0.025). No statistically significant correlation was found in the subgroup analyses. In the second multivariate analysis, no significant correlation was found between PAT and CCT, Km, age or sex (P>0.05). In the third analysis, densitometry was correlated with age in all glaucoma subgroups (P<0.001) and with CCT in the moderate glaucoma subgroup (coef. -0.037; IC [-0.67-(-0.01)]; P=0.021). Tonometry appeared to be minimally influenced by corneal densitometry, with a mild positive linear correlation seen (R=0.03). IOP values were similar with 3 of the tonometers: PAT 16.07 (±3.18) mmHg, PRO 16.27 (±3.42) mmHg and ic100 15.17 (±4.28) mmHg. There was, however, a significant underestimation of IOP with ic100 (-0.89mmHg) compared to PAT (P=0.007). CONCLUSION: Corneal densitometry did not show significant differences between glaucoma severity groups. A positive correlation was seen with CCT and both corneal densitometry and age. No correlation was found with keratometry or severity of glaucoma. The influence of corneal densitometry on IOP measurements appears weak, with little clinical relevance identified.

Glaucoma progression. Clinical practice guide.

OBJECTIVE: To provide general recommendations that serve as a guide for the evaluation and management of glaucomatous progression in daily clinical practice based on the existing quality of clinical evidence. METHODS: After defining the objectives and scope of the guide, the working group was formed and structured clinical questions were formulated following the PICO (Patient, Intervention, Comparison, Outcomes) format. Once all the existing clinical evidence had been independently evaluated with the AMSTAR 2 (Assessment of Multiple Systematic Reviews) and Cochrane "Risk of bias" tools by at least two reviewers, recommendations were formulated following the Scottish Intercollegiate Guideline network (SIGN) methodology. RESULTS: Recommendations with their corresponding levels of evidence that may be useful in the interpretation and decision-making related to the different methods for the detection of glaucomatous progression are presented. CONCLUSIONS: Despite the fact that for many of the questions the level of scientific evidence available is not very high, this clinical practice guideline offers an updated review of the different existing aspects related to the evaluation and management of glaucomatous progression.

Budget impact analysis of the XEN®63 for the treatment of primary openangle glaucoma in Spain.

BACKGROUND AND OBJECTIVE: To evaluate the economic impact in Spain derived from the introduction of the XEN®63 implant as a surgical alternative in the management of primary open angle glaucoma (POAG) with or without cataract in refractory patients. MATERIALS AND METHODS: A budget impact analysis was designed to estimate the costs of surgical treatment of POAG from the perspective of the Spanish National Health System (NHS), over a time horizon of 1 year. The comparators considered (trabeculectomy, deep non-penetrating sclerectomy, Ahmed valve, iStent inject, Preserflo® microshunt and XEN®45) correspond to those used in Spanish public clinical practice. For the calculation of the target population, market shares and resource use in terms of follow-up visits, additional procedures and post-surgery complications, data from the literature were used and validated with a panel of 4 experts. Unit costs (€ 2021) were obtained from the ESALUD database. RESULTS: The inclusion of XEN®63 could generate savings of €2,569,737 after one year since its introduction, derived from savings in the cost of the implant and procedure (-€423,120; -0.7%), follow-up visits (-€777,407; -4.5%), additional procedures (-€1,048,145; -20.6%) and post-surgery complications (-€321,065; -14.2%). CONCLUSIONS: The incorporation of XEN63®in the surgical arsenal for the treatment of refractory POAG with and without cataracts could generate savings for the NHS.

Posterior chamber implantation of a Preserflo Microshunt in a patient with a compromised endothelium.

The objective of the present case is to describe a variation in the Preserflo Microshunt surgical technique, placing it in the posterior chamber to minimise the risk of endothelial cell loss in cases with a compromised endothelium. The patient was a 72-year-old pseudophakic woman, with granular dystrophy and a primary diagnosis of open-angle glaucoma presenting with a progressive visual field defect and an IOP of 26 mmHg with maximal medical therapy. The cornea had incipient stromal folds with an endothelial count of 700 cells/mm2. A Preserflo Microshunt was implanted in the posterior chamber to minimise the possibility of further damage to the corneal endothelium. Six months after surgery, the implant remains functional. The IOP is 9 mmHg without medications. As far as we know, this is the first Preserflo implanted in the posterior chamber described in the literature.

Reproducibility of SD-OCT inner macular layer thickness measurements in children with primary congenital glaucoma.

PURPOSE: To examine the reproducibility of spectral domain optical coherence tomography (SD-OCT) segmented ganglion cell complex and circumpapillary retinal nerve fiber layer (cpRNFL) measurements in children with primary congenital glaucoma (PCG) in comparison with healthy children. METHODS: 12 children with PCG (G1) and 24 healthy children (G2) were recruited. The following SD-OCT measurements (Spectralis, Heidelberg Engineering) were made in one eye per child: total macular thickness (MT), thicknesses in several subfields and volumes of the three inner macular layers, macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) and cpRNFL thickness. In a single day, an expert operator obtained 3 circumpapillary and 3 macular measurements in each participant to determine intraoperator variability. Intraoperator repeatability was defined by the coefficient of variation (CoV) and intraclass correlation (ICC). RESULTS: ICC was excellent in both groups for cpRNFL measurements (G1 ICC=0.950 and G2 ICC=0.995) and for MT was excellent in G1 (ICC=0.957) and moderate in G2 (ICC=552). For the inner macular layer measurements, all ICCs were better in PCG group (mRNFL-ICC: 0.915 vs. 0.765; ICC-GCL: 0.584 vs. 0.263 and ICC-IPL: 0.979 vs. 0.742; G1 and G2 respectively). Greater CoV were recorded for macular measurements (from 0.71% to 9.82%) compared to cpRNFL measurements (from 0.52% to 1.50%). CONCLUSION: In children with PCG, Spectralis SD-OCT showed excellent intrasession repeatability for cpRNFL, MT, mRNFL and IPL measurements and moderated for GCL measurements. For all macular measurements, ICC were higher in children with PCG than healthy children.

Photosensitive ganglion cells: A diminutive, yet essential population.

Our visual system has evolved to provide us with an image of the scene that surrounds us, informing us of its texture, colour, movement, and depth with an enormous spatial and temporal resolution, and for this purpose, the image formation (IF) dedicates the vast majority of our retinal ganglion cell (RGC) population and much of our cerebral cortex. On the other hand, a minuscule proportion of RGCs, in addition to receiving information from classic cone and rod photoreceptors, express melanopsin and are intrinsically photosensitive (ipRGC). These ipRGC are dedicated to non-image-forming (NIF) visual functions, of which we are unaware, but which are essential for aspects related to our daily physiology, such as the timing of our circadian rhythms and our pupillary light reflex, among many others. Before the discovery of ipRGCs, it was thought that the IF and NIF functions were distinct compartments regulated by different RGCs, but this concept has evolved in recent years with the discovery of new types of ipRGCs that innervate subcortical IF regions, and therefore have IF visual functions. Six different types of ipRGCs are currently known. These are termed M1-M6, and differ in their morphological, functional, molecular properties, central projections, and visual behaviour responsibilities. A review is presented on the melanopsin visual system, the most active field of research in vision, for which knowledge has grown exponentially during the last two decades, when RGCs giving rise to this pathway were first discovered.

Comparision of intraocular pressure measured using the new icare 200™ rebound tonometer and the Perkins™ applanation tonometer in healthy subjects and in patients with primary congenital glaucoma. / Comparación entre el tonómetro de rebote IC200 y el tonómetro de aplanación Perkins en sujetos sanos y pacientes con glaucoma congénito.

OBJECTIVE: To compare intraocular pressure (IOP) measurements obtained using the Icare 200™ (IC200) rebound tonometer and the hand-held version of the Goldmann Applanation Tonometer (Perkins™ tonometer, GAT) in patients with primary congenital glaucoma (PCG) and in healthy subjects. MATERIAL AND METHODS: A total of 42 eyes of healthy subjects (G1) and 40 patients with PCG (G2) were analysed. The following clinical data were collected: gender, age, Cup/Disc ratio, central corneal thickness (CCT). IOP was determined in the examination room using the IC200 and GAT tonometers, in the same order. Agreement between both tonometers was determined using the intraclass correlation coefficient (ICC) and Bland-Altman plot. A linear regression analysis was used to establish the IOP was affected by the studied variables. RESULTS: Mean IOP between both tonometers (IC200 minus GAT) was: G1=15.91 (2.57) mmHg vs. 15.06 (2.12) mmHg (mean difference, MD=0.84 (0.50) mmHg; P<.101) and G2=20.10 (6.37) vs.19.12 (5.62) (MD=0.98 (1.36); P=.474). Excellent agreement was found between IC200 and GAT in both groups (ICC=G1: 0.875 (95% CI; 0.768-0.933; P<.001); G2: 0.924 (95% CI; 0.852-0.961; P<.001), and there was a statistically significant correlation between the IOP difference measured with IC200 and GAT and CCT in G1 (B=0.021; 95% CI; 0.005-0.037; P=.008), but was not statistically significant in G2. CONCLUSION: There was excellent agreement between the IC200 and GAT tonometers, both in healthy subjects and PCG, with a trend to overestimate IOP when measured with IC200. There was no influence by CCT on IOP measurements in patients with PGC.

Corneal densitometry and topography in patients with primary congenital glaucoma.

OBJECTIVE: To compare corneal densitometry and topography variables in patients with primary congenital glaucoma (PCG) and healthy subjects. MATERIAL AND METHODS: Cross sectional study, consecutive recruitment with gender- and age-matched control group. Forty eyes of 40 patients in each group were studied with Pentacam corneal topography. The variables compared between the two groups were: intraocular pressure (IOP), visual acuity (VA) and Pentacam (Oculus, Wetzlar, Germany) corneal topography measurements: mean and maximum keratometry (Km, Kmax), cylinder (Cyl), anterior elevation apex (AEA), central anterior elevation (CAE), maximum anterior elevation (MAE), posterior elevation apex (PEA), central posterior elevation (CPE), maximum posterior elevation (MPE), pachymetry and anterior, mid-stromal and posterior corneal densitometry in the 0-2mm, 2-6mm, 6-10mm zones. RESULTS: Significant differences between patients and healthy controls were detected in the topographic variables MAE (P=0.002) and MPE (P<0.001), and in all the densitometry variables (anterior, mid-stromal, posterior for the 0-2mm, 2-6mm and 6-10mm zones) (P<0.001 each). In the PCG group, negative correlation was observed between VA and total densitometry (r=-0.49; P=0.004). CONCLUSION: Patients with PCG and healthy subjects display differences in corneal densitometry and topographic measurements. PCG patients show greater corneal density with an inverse relationship between visual acuity and higher elevation (anterior and posterior values).

Structure-function relationship in a series of glaucoma cases.

PURPOSE: To map retinal sensitivity and peripapillary retinal nerve fiber layer (RNFL) thickness, as measured by standard automated perimetry (SAP) and optical coherence tomography (OCT) respectively, in patients with various stages of primary open-angle glaucoma (POAG). METHODS: Ninety patients with POAG were prospectively selected for SAP and for OCT RNFL thickness measurements. Factorial analysis performed independently for each hemifield was used to identify groups of related SAP visual field points. Pearson correlation coefficients were determined between visual field regions and peripapillary RNFL sectors and these data used to construct structure-function correlation maps for the various disease stages. RESULTS: Factorial analysis identified 4 factors or visual field regions for the inferior hemifield and 5 for the superior hemifield. For all patients and the subset of patients with advanced POAG, the strongest correlation was detected between the superior hemifield and the inferior RNFL sectors, while higher correlations for incipient and moderate disease stages were observed between the inferior hemifield and the superior RNFL sectors. CONCLUSIONS: In these patients, functional and structural damage can be mapped such that each zone of related SAP points correlates with one or several peripapillary RNFL zones. Such maps could improve our understanding of structure-function relationships in glaucoma.

The correlation between the thickness of the inner macular layers and the mean deviation of the visual field in children with primary congenital glaucoma. / Correlación entre el grosor de las capas internas de la retina y el defecto medio del campo visual en pacientes con glaucoma congénito primario.

PURPOSE: To analyse the association between the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the thickness of the inner macular layers with the mean deviation of the visual field (MD) in children with primary congenital glaucoma (PCG). MATERIAL AND METHODS: A total of 41 children with PGC were included in the study. They all had a complete ophthalmological examination, including visual acuity, intraocular pressure, funduscopy, Octopus™ visual field, as well as circumpapillar and macular spectral domain optical coherence tomography (SD-OCT). SD-OCT with automated segmentation was used to measure the thicknesses and volumes of the macular retinal nerve fibre layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer. RESULTS: The mean age was 11.2±3.86 years, and the mean MD was 8.85±6.76dB. The visual field was classified as normal in 46% of the patients, and 20% of the patients had a concentrical restriction of the visual field. A positive correlation was found between between the cup-to-disc ratio and the MD, r=0.51 (P=.004). The correlation between the MD and the cpRNFL was r=-0.63 (P<.001), and r=-0.69 (P<.001) with the GCL. CONCLUSIONS: Inner macular layers thickness and cpRNFL thickness show a good correlation with the mean deviation of the visual field in children with primary congenital glaucoma.