The Increased Burden of Rare Variants in Four Matrix Metalloproteinase-Related Genes in Childhood Glaucoma Suggests a Complex Genetic Inheritance of the Disease.

Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with a poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including CPAMD8 and ADAMTSL4, compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of adamtsl4 and cpamd8 zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinase-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.

Efficacy and safety of the PreserFlo implant with mitomycin C in childhood glaucoma after previous failed glaucoma surgeries.

PURPOSE: This study aims to evaluate the efficacy and safety of the PreserFlo MicroShunt (Santen, Osaka, Japan) in lowering intraocular pressure (IOP) in childhood glaucoma patients with previous failed glaucoma surgeries. METHODS: This is a prospective case review of consecutive PreserFlo procedures performed in childhood glaucoma patients after failed surgeries. Age, sex, diagnosis, and previous glaucoma surgeries, as well as visual acuity, IOP, and treatment in the preoperative visit and all follow-up visits were collected. Outcome measures included IOP reduction from baseline, mean IOP change from baseline at month 6, medication use at 6 months, complications, adverse events, and need for further procedures. RESULTS: Fourteen patients were included, 8 (57%) males and 6 (43%) females; the mean age was 27.5 ± 13.5 years. Nine patients (64%) had at least two trabeculectomies, and 6 patients (43%) had at least one trabeculectomy and a glaucoma drainage implant. The mean IOP change from baseline was 11.3 ± 4.9 mmHg at 12 months. At 12 months, 12 patients (86%) presented ≥ 20% IOP lowering from baseline, and 11 patients (79%) presented ≥ 30%. The mean medication count decreased from 3.9 ± 0.7 (baseline) to 0.7 ± 1.3 (12 months). No intraoperative complications were reported. No adverse events were noted. No secondary filtration surgery was required, although bleb needling was required in one case, 1 month after the surgery. CONCLUSIONS: PreserFlo with MMC can be used successfully to treat uncontrolled IOP in childhood glaucoma cases with previous failed surgeries. Larger studies with longer follow-up are needed to further explore the role of the device in resistant childhood glaucoma cases.

Comparison of intraocular pressure measurements between Easyton transpalpebral tonometry and Perkins, iCare iC100 and Corvis ST, and the influence of corneal and anterior scleral thickness.

PURPOSE: To compare intraocular pressure (IOP) measurements between Easyton transpalpebral tonometry and Perkins, iCare iC100 and Corvis ST. Also, to assess the influence of corneal characteristics and anterior scleral thickness (AST) on the IOP measurements. METHODS: Sixty-nine eyes from 69 healthy subjects were included. IOP was measured by Easyton, Perkins, iC100 and Corvis ST (corrected IOP, bIOP; and non-corrected IOP, IOPnct). Other variables studied were AST, axial length (AL), and Corvis parameters: Length 1, velocity 1, length 2, velocity 2, peak distance, radius, deformation amplitude, and central corneal thickness (CCT). Pearson correlation, limits of agreement (LoA), and multiple regression analysis were calculated. RESULTS: No significant differences in IOP between Easyton and Perkins, iC100, and bIOP were observed (all p > 0.05), being significant only between Perkins and IOPnct ( - 1.49 mmHg, p < 0.001). Bland-Altman graphs showed that the mean difference between Perkins and Easyton was 0.07 mmHg (p < 0.001), and LoA - 7.49 to + 7.39 mmHg. Significant correlations were found between the measurements of Perkins and iC100, IOPnct, bIOP (r = 0.710, 0.628, 0.539; p < 0.001 respectively), iC100 and IOPnct, bIOP (r = 0.627, 0.513; p < 0.001, respectively). The multivariate regression analysis revealed that differences between Perkins and Easyton (adjusted R2 = 0.25) were influenced by AL (B = 1.28, p < 0.008), length 1 (B = 3.13, p < 0.018), and the radius (B = 1.26, p < 0.010). Differences between Perkins and bIOP (adjusted R2 = 0.21) were affected by the CCT (B = 0.029, p < 0.003). CONCLUSIONS: There are no significant differences in the IOP measurements between Perkins and Easyton, iC100 or bIOP. Length 1, radius, and CCT have limited influence on these differences, while AST did not show any effect.

Easyton® transpalpebral versus Perkins applanation tonometry in different populations.

OBJECTIVE:  To compare intraocular pressure (IOP) measurements obtained using the new transpalpebral Easyton® tonometer and Perkins applanation tonometer (PAT) in three different clinical populations. METHODS: The participants of this prospective study were 84 subjects divided into the groups: 22 healthy children (G1), 42 healthy adults (G2), and 20 adult patients with primary open angle glaucoma (G3). The data recorded in 84 eyes of these subjects were age, sex, gender, central corneal thickness (CCT), and axial length (AL). In all eyes, IOP was determined in the same examination room by the same experienced examiner using Easyton® and PAT in random order. RESULTS:  Mean differences in IOP readings between Easyton® and PAT were 0.45 ± 1.97 (p = 0.295), - 0.15 ± 2.13 (p = 0.654), - 1.65 ± 3.22 (p = 0.033), and - 0.018 ± 2.50 mmHg (p = 0.500) in the groups G1, G2, G3, and whole sample (G4), respectively. Correlations between Easyton® and PAT IOP values were 0.668 (p = 0.001) for G1, 0.463 (p = 0.002) for G2, 0.680 (p < 0.001) for G3, and 0.605 (p < 0.001) for G4. Moderate to good agreement between the two tonometers was found in all groups according to intraclass correlation coefficients, which were 0.794 (p < 0.001) for G1, 0.632 (p < 0.001) for G2, 0.809 (p < 0.001) for G3, and 0.740 (p < 0.001) for G4. The lower and upper limits of agreement between the devices were - 5.1 and 4.7 mmHg, respectively, in the complete group. No correlation was noted between CCT or AL and the Easyton® IOP measurements. CONCLUSION: IOP measurements obtained with Easyton® and PAT show an acceptable level of agreement mainly in healthy individuals, recommending it for IOP screening in children and in patients in which PAT measurement may be impared as patients with hemifacial spasms, corneal irregularities, or reduced mobility. It is not recommended for glaucoma patients follow-up.

Twelve-month results of ab interno trabeculectomy with Kahook Dual Blade: an interventional, randomized, controlled clinical study.

PURPOSE: To evaluate the efficacy and safety profile of Kahook Dual Blade ab interno trabeculectomy combined with phacoemulsification compared to stand-alone conventional cataract surgery. METHODS: A single-center longitudinal, randomized controlled trial was conducted. Patients older than 18 years with coexisting cataract and open-angle glaucoma or ocular hypertension were invited to participate. Preoperative and postoperative clinical data were collected and analyzed preoperatively and at months 1, 3, 6, and 12 after the procedure. Main outcome measures included best corrected visual acuity, intraocular pressure, number of glaucoma medications, endothelial cell count, and standard automated perimetry. RESULTS: Forty-two eyes from 33 patients were randomly allocated to the combined cataract and KDB (treatment, n = 21) or cataract alone (control, n = 21) groups. Intraocular pressure decreased from 17.9 ± 3.5 to 16.0 ± 2.2 mmHg and from 17.3 ± 2.5 to 15 ± 3.2 mmHg at the last visit in the treatment and control groups (p = 0.47). The use of glaucoma medications was reduced from a median (IQR) 1 (1-2) to 0 (0-0) in the treatment group and from 1 (1-2) to 0 (0-1) in the control group, with no significant differences between groups at the 12-month visit (p = 0.47). Best corrected visual acuity, endothelial cell count, and standard automated perimetry remained similar during follow-up in both groups. CONCLUSIONS: In patients with well-controlled, mild-to-moderate glaucoma, adding ab interno trabeculectomy with KDB to phacoemulsification might not be more effective than phacoemulsification alone to reach mid-teens IOP values. Both procedures showed similar safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04202562, December 17, 2019 retrospectively registered.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients' features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.

Improvement of objective ocular redness measured with Keratograph 5M in glaucoma patients after instilling brimonidine drops.

OBJECTIVE: To compare objective ocular redness measured using OCULUS Keratograph 5 M before and after 0.2% brimonidine instillation in glaucoma patients under topical hypotensive treatment. METHODS: 60 eyes from 60 subjects diagnosed with glaucoma or ocular hypertension under hypotensive ocular topical treatment were analyzed. Basal Ophthalmological examination was performed.Outcome variables were OCULUS Keratograph 5 M redness scores (RS) before and after 0.2% brimonidine instillation; overall, bulbar temporal (BT), bulbar nasal (BN), limbar temporal (LT), and limbar nasal (LN); non-invasive average tear film breakup time (Nia-BUT), non-invasive first tear film breakup time (Nif-BUT) and meibography. In addition, the following clinical data were collected: intraocular pressure, type, duration, amount, and preservatives/or not of hypotensive treatment, fluorescein corneal staining score and lower tear meniscus height. RESULTS: All eyes were under topical medication. All redness scores were reduced after brimonidine instillation, mean RS differences were BT 0.82 ± 0.62, BN hyperemia 1.03 ± 0.55, LN hyperemia 0.84 ± 0.49, LT hyperemia 0.71 ± 0.50 and total hyperemia 0.91 ± 0.52 (all p < 0.001). 30 min after brimonidine instillation mean overall RS reduction was 47.97 ± 12.39% (p < 0.001) and after 1 h there was a persistent reduction of overall RS of 45.92 ± 14.27% (p < 0.001). Hyperemia reduction was significant and comparable between preservative and preservative-free group 0.12 ± 0.14 (p > 0.392) and between patient with combination therapy and monotherapy 0.16 ± 0.14 (p > 0.258). CONCLUSION: A significant reduction of conjunctival hyperemia was objectively found in glaucoma patients under topical hypotensive treatment before and after brimonidine instillation. Its fast and long-lasting effect may be useful preoperatively in glaucoma patients to reduce intraoperative bleeding and associated complications.

Trends in glaucoma surgery in a tertiary hospital in Spain: 2010-2022.

OBJECTIVE: This study aims to conduct an analysis glaucoma surgeries performed over a 13-year period at a tertiary hospital affiliated with the Spanish National Health System, with the goal of assessing temporal trends. METHODS: This retrospective observational study scrutinized surgeries undertaken in the glaucoma unit of a tertiary center in Spain between 2010 and 2022. Data collected included surgical dates, procedure performed, whether it was standalone or combined, as well as patient demographics including age, sex, and type of underlying glaucoma. Surgeries on individuals under 18 years of age were excluded. An annual comparative analysis was performed to ascertain the evolving trends in glaucoma surgical interventions. RESULTS: A total of 12,944 surgeries were included in the analysis, comprising 9428 isolated cataract surgeries and 2975 glaucoma procedures. Trabeculectomy, glaucoma drainage devices (GDD), and cyclodestruction, collectively referred to as traditional surgery, demonstrated a decline from 93.2% to 23.6% over the study duration. Minimally invasive glaucoma surgery (MIGS) and minimally invasive bleb surgery (MIBS) demonstrated a significant increase from 3.8% in 2010 to 74.7% in 2022, relative to the total glaucoma surgeries. Furthermore, combined surgeries manifested a noteworthy increase from 39.0% in 2010 to 44.2% in 2022, with 86.4% of combined procedures in 2022 being MIGS or MIBS. CONCLUSION: In recent years, there has been a noticeable change in the trend of glaucoma surgeries, with MIGS and MIBS procedures experiencing a significant increase and becoming the most commonly performed glaucoma procedures. Consequently, traditional glaucoma surgeries have decreased in frequency.

Intraoperative OCT to check the correct postimplant position of PreserfloTM.

INTRODUCTION: This study was designed to examine the capacity of intraoperative optical coherence tomography (OCT) to predict the postimplant position of the glaucoma drainage device PreserfloTM. METHODS: 13 eyes (mean age 65.42 (14.89) years) underwent PreserfloTM (Santen, Osaka, Japan) placement. Before surgery, participants were subjected to a comprehensive ophthalmic examination (intraocular pressure (IOP), cup to disk ratio (C/D), visual field, OCT, endothelial cell count). Anterior segment OCT scans were obtained intraoperatively using a Rescan 700 OCT system (Carl Zeiss Meditec, Inc., Oberkochen, Germany). One day postsurgery, anterior segment OCT using the Spectralis OCT (Heidelberg Engineering GmbH) was performed in a sitting position to capture the same chamber cross-section as before. The main outcome variables were tube-endothelium distance (T-E) and tube length (TL) in the anterior chamber measured using both OCT systems. Correlation between intraoperative and office measurements was examined through Pearson correlation (r) and intraclass correlation coefficients (ICC). RESULTS: Mean intraoperative and in-office T-E were 625.26 (SD 366.60) versus 561.16 (SD 364.62) µm respectively (p = 0.540). Intraoperative and in-office anterior chamber TL were 1386 (SD 701.82) and 1433.91 (SD 713.55) µm, respectively (p = 0.029). Excellent correlation was observed between both sets of T-E (r = 0.992; p = 0.008) and TL (r = 0.984; p = 0.016) values. Both OCT systems showed good agreement yielding ICCs of 0.992 (p < 0.001) for T-E and 0.995 (p = 0.001) for TL. DISCUSSION: Excellent correlation was observed between our intraoperative and postoperative OCT measurements. These results support the usefulness of intraoperative OCT to confirm the correct position of an implanted PreserfloTM microshunt.

Prescription trends for preservative free glaucoma medication in a public health system.

PURPOSE: To analyze the prescribing trends over a 7-years period, between 2013 and 2020, in a tertiary hospital (Hospital Clinico San Carlos, Madrid, Spain) and its health area. MATERIAL AND METHODS: A retrospective study on the data collected from the information systems, "farm@web" and "Farmadrid", of glaucoma prescriptions in the framework of a public health system (Spanish National Health System) during the last seven years. RESULTS: Prostaglandin analogues were the most commonly used drugs in monotherapy during the study period (range: 36.82% - 47.07%). Fixed combinations of topical hypotensives had an upward trend since 2013 (range: 39.99% - 54.21%), becoming the most dispensed drugs in 2020 (48.99%). Preservative-free eye drops (lacking benzalkonium chloride, BAK) have displaced preservative containing topical treatments in all pharmacological groups. In 2013, BAK-preserved eye drops accounted for 91.1% of the total prescriptions, however in 2020 they only accounted for 34.2% of total prescriptions. CONCLUSIONS: The results of the present study highlight the current trend to avoid BAK-preserved eye drops for the treatment of glaucoma.

Basal evaluation and rates of progression based on visual fields in six different glaucoma types of a large population.

PURPOSE: The aim of this study is to analyze the distribution of visual field (VF) mean defect (MD) in six subgroups of glaucoma patients at baseline and follow-up. METHODS: We assessed glaucoma patients treated in a Spanish tertiary care setting with a follow-up of at least 10 months. We have included 1036 visual fields and the following glaucoma subtypes: open-Angle Glaucoma (OAG); Angle-Closure Glaucoma (ACG); Congenital Glaucoma (CG); Ocular hypertension (OHT); Pseudoexfoliative Glaucoma (PSXG); Pigmentary Glaucoma (PG). We have calculated the baseline MD and the progression MD. We have stratified the MD progression in slow (MD rate > -0.5 dB/year); moderate (MD rate between -0.5 and -1 dB/year) fast (MD rate between -1 and -2 dB/year) and catastrophic (<-2 dB/year) progression and their glaucoma subtype. RESULTS: The glaucoma types with the worse baseline MD were CG and PG. We found significant differences after comparing the baseline MD of CG and OAG, ACG, OHT and between PG and OHT. Concerning the MD progression rate: OAG 73.54% showed slow MD progression rate; 9.85% fast; 7.3% moderate and 9.3% catastrophic. ACG 82.22% slow; 8.89% moderate; 2.22% fast and 6.67% catastrophic. CG 68.83% slow; 9.09% fast; 7.79% moderate and 14.29% catastrophic. OHT 88.6% slow; 6.14% moderate; 4.39% fast and 0.88% catastrophic. PSXG 63.24% slow, 13.24% moderate; 8.8% fast and 14.7% catastrophic. PG 89.29% slow; 3.57% moderate and 7.1% fast. CONCLUSIONS: The CG requires special attention because of its aggressive presentation and progression.

Null CYP1B1 genotypes in primary congenital and nondominant juvenile glaucoma.

PURPOSE: To assess the mutation spectrum, enzymatic activity, and phenotypic features associated with CYP1B1 genotypes in primary congenital glaucoma (PCG) and nondominant juvenile glaucoma (ndJG). DESIGN: CYP1B1 genotyping, segregation analysis, and functional evaluation of mutations in a cohort of patients. PARTICIPANTS: A total of 177 probands clinically diagnosed with PCG (161) or ndJG (16). METHODS: Automatic DNA sequencing of the promoter (-1 to -867) and the 3 CYP1B1 exons. CYP1B1 enzymatic activity was evaluated using an ethoxyresorufin O-deethylation assay in transfected HEK-293T cells. MAIN OUTCOME MEASURES: Screening and functional evaluation of CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, measurement of intraocular pressure, gonioscopy, and fundus examination. RESULTS: Thirty-one different mutations were identified in 56 PCG and 7 ndJG index cases. To the best of our knowledge, 3 of the identified mutations were novel (-337G>T, F123L, and I399_P400del). Approximately 56% of all mutation carriers were compound heterozygotes, 25% were homozygotes, and both groups inherited glaucoma as an autosomal recessive trait. Nineteen percent of carriers were heterozygotes and showed non-Mendelian segregation. In vitro and inferred functional analysis showed that no less than approximately 74% of the recessive genotypes result in null enzymatic activity. We detected variable expressivity in relation to age of onset and a possible case of incomplete penetrance in 3 of 6 families (50%), with more than 1 affected child or more than 1 subject carrying 2 CYP1B1 mutant alleles. Altogether, these data support that PCG is not a simple monogenic disease. In addition, most patients with PCG carrying null or putative null genotypes showed severe bilateral phenotypes featured by early disease onset, frequently at birth. The mean number of trabeculectomies per eye was significantly higher in carriers than in noncarriers. CONCLUSIONS: This is the largest analysis of CYP1B1 mutations performed in European patients with PCG to date. Our data show that null CYP1B1 genotypes, and therefore complete absence of CYP1B1 activity, frequently lead to severe phenotypes. Our results support that CYP1B1 glaucoma is not a simple monogenic disease and that CYP1B1 activity levels could influence the phenotype.

Bleb geometry and morphology after Preserflo Microshunt surgery: Risk factors for surgical failure.

PURPOSE: To investigate the possible risk factors for treatment failure in patients who had undergone Preserflo Microshunt (PMS) implantation, using anterior-segment optical coherence tomography (AS-OCT) to analyze the internal structures of the bleb. METHODS: The PMS blebs of 54 patients were evaluated with AS-OCT. A mathematical model was used to calculate the total filtering surface of the episcleral fluid cavity (EFC) and the hydraulic conductivity (HC) of the bleb wall. Complete and qualified success were defined as IOP between 6 and 17 mmHg with or without glaucoma medication. The relation between baseline characteristics and probability of bleb success was analyzed by bivariate and multivariate logistic regression. The main outcome measures were mean bleb wall thickness (BWT), reflectivity (BWR), HC, mean horizontal and vertical diameter and total filtering surface (TFS) of the EFC. RESULTS: Blebs from 74% patients were considered as complete success and 26% as failure. BWR and BWT increased linearly up to the first year in both groups. BWR was higher in the group failure (p = 0.02) and BWT in the group success (p<0.001). EFC was wider and shorter in the success group (p = 0.009, p = 0.03). Higher TFS showed a negative correlation with IOP (r = -0.4, p = 0.002). Higher baseline IOP was associated with success of PMS by multivariate analysis (p = 0.01). Mean HC, 0.034 ± 0.008 (µL/min)/mm2/mmHg, was negatively correlated with bleb surface (r = -0.5, p<0.0001) and wall´s thickness (r = -0.3, p = 0.01). CONCLUSIONS: AS-OCT revealed that successful PMS blebs could show either thick hyporreflective walls or wide filtering surfaces with thin capsules. A higher baseline IOP increased the probability of surgical success.

Corneal Biomechanics in Non-infectious Uveitis Measured by Corvis ST: A Pilot Study.

PURPOSE: To assess differences between corneal biomechanical properties in patients with non-infectious uveitis and healthy subjects using CorVis. METHODS: 77 patients with non-infectious uveitis and 47 control subjects were recruited. Biomechanical parameters were measured: deformation amplitude (DA), A-1 length and A-2 length (L1, L2), A-1 velocity and A-2 velocity (V1, V2), peak distance (PD) and HC radius (highest concavity radius). AUC ROC and correlation between clinical variables and biomechanical properties were determined. RESULTS: Lower HC Radius and IOPb and higher DA and V1 was found in uveitis group. Statistical differences between cases using systemic medications and those with topical treatment were found in L1. Differences were showed between those cases with active and inactive uveitis in PD, DA, V2 and L2. The biomechanical parameter with the best discriminatory capacity of uveitis disease was HC Radius. CONCLUSION: Differences in corneal biomechanical properties between non-infectious uveitis and healthy eyes were found.

Peripapillary and macular vascular parameters by optical coherence tomography angiography in primary congenital glaucoma.

OBJECTIVE: To evaluate the differences in peripapillary and macular vascular parameters by optical coherence tomography angiography (OCTA) between patients with primary congenital glaucoma (PCG) and healthy controls; and to determine their diagnostic accuracy. MATERIAL AND METHODS: Observational, cross-sectional study including 39 eyes with PCG and 78 healthy eyes. Only one eye per patient was included. All included patients underwent a comprehensive ophthalmic examination and peripapillary and macular analysis were performed by AngioplexTM OCTA (Cirrus HD-OCT 5000) with a 4.5 × 4.5 mm optic nerve head scan and 6 × 6 mm macular scan. Global data and quadrant data from peripapillary vascular parameters and global data and circular sectors data from macular superficial plexus parameters were compared between groups. The glaucoma discrimination capability of these parameters was calculated as areas under the receiver operating characteristics curve (AUC ROC). RESULTS: Mean age was 14.1 ± 8.7 years for the PCG patients and 11.7 ± 6.2 years for controls (p = 0.093). All vascular peripapillary measurements (global and quadrants; all p < 0.001) and all macular measurements (p < 0.042) excepting perfusion density in the inner circle (p = 0.087), were reduced in the PCG group compared to controls. According to AUC ROC, peripapillary (all ≥ 0.706) and macular parameters (all ≥ 0.699) showed good diagnostic capacity. AUC ROC for the most discriminatory measurements corresponding to blood flux index (0.887) and whole macula vascular density (0.855) were similar (p = 0.085). CONCLUSION: Peripapillary and macular vascular parameters by OCTA are decreased in patients with PCG, showing a good capacity to discriminate between normal and glaucomatous eyes.

Corneal Endothelial Cell Loss After PRESERFLO™ MicroShunt Implantation in the Anterior Chamber: Anterior Segment OCT Tube Location as a Risk Factor.

INTRODUCTION: To analyze the effects of PRESERFLO on corneal endothelial cell density (ECD). METHODS: Forty-six eyes that underwent PRESERFLO implantation were followed up for 12 months. Specular microscopy was performed preoperatively and at 1, 3, 6, and 12 months postoperatively to measure central ECD and mean monthly reduction (MMR). Anterior segment optical coherence tomography (AS-OCT) was applied to measure the tube-endothelium (TE < 200 µm, 201-500 µm, > 500 µm) distance. The relationship between TE distance and ECD was analyzed with a linear mixed-effects model. RESULTS: Central ECD decreased significantly at 1 year (7.4%, p = 0.04), with an MMR of -15 ± 25 cells/mm2. Regarding TE distance groups, there was an 18% ECD reduction in the < 200 µm group vs. 1% in the > 500 µm group (p = 0.08). Endothelial cell loss was related to TE distance (mean 482.9 ± 238 µm), with a higher rate at 1 month in comparison to 12 months for the same tube position in the anterior chamber (-174.8 ± 65.2 cells/mm2 at 1 month vs. 30.2 ± 11.3 cells/mm2 at 12 months, p < 0.01). From month 6, tubes located > 600 µm from the endothelium showed EC loss close to zero. CONCLUSIONS: The PRESERFLO implant is associated with a loss of EC from the immediate postoperative period that continues over time at lower rates. A shorter TE distance appears to cause more severe ECD loss.

Evaluation of a Novel Αb Εxterno MicroShunt for the Treatment of Glaucoma.

The surgical management of glaucoma has been revolutionized by the introduction of minimally invasive glaucoma surgery (MIGS). The various MIGS options aim to meaningfully lower intraocular pressure with a better safety profile than traditional glaucoma surgery. The key clinical attributes and the emerging potential of an ab externo MicroShunt (PreserFlo™) are reviewed in the context of published evidence and clinical experience. This novel MicroShunt consists of an 8.5-mm-long tube that is implanted in the eye via an ab externo approach enabling aqueous humor drainage into the sub-Tenon's space through the formation of a bleb, similar in appearance to that created by trabeculectomy. The efficacy and safety of this procedure, the concomitant use of antimetabolites, the impact of tube positioning, and its future value in clinical practice are critically reviewed. Recent evidence has demonstrated the MicroShunt to be less effective than traditional filtration surgery, but with a significant improvement in safety. Cumulative data suggest that the new implant provides tangible clinical benefits to selected patients with glaucoma in need of further intraocular pressure (IOP) lowering. Future research should delineate the precise role of this and other MIGS options in the rapidly evolving glaucoma treatment algorithm.

Intense pulsed light-based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops.

BACKGROUND: Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40% to 59% of these patients worldwide. The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light (IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments. To our knowledge, this is the first series analyzing the therapeutic effect of this treatment option in this type of patients. METHODS: This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology. All patients received four sessions of IPL treatment using the Optima IPL system (Lumenis, Yokneam, Israel) adjusted to the official optimized Lumenis setting. Changes in symptomatology, corneal staining, conjunctival hyperemia, non-invasive break-up time (NIBUT), tear osmolarity, tear meniscus height (TMH), meiboscore and meibomian gland expressibility was analyzed after treatment. RESULTS: Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires [ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED) and symptom assessment questionnaire in dry eye (SANDE)] as well as with the visual analogue scale (P < 0.001). Mean change in OSDI was - 15.0 ± 11.3. A significant reduction was found after treatment in the corneal staining score (P < 0.001). A significant reduction was found in tear film meniscus height (P = 0.012), as well as in tear film osmolarity (P = 0.001). A significant reduction was also found in meibomian gland expressibility (P = 0.003), changing the percentage of grade 3 eyes from 44.4% before IPL to 17.2% after treatment. CONCLUSIONS: IPL therapy combined with meibomian gland expression (MGX) seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments, with an additional improvement in clinical signs, such as tear osmolarity and corneal staining.

Effects of Corneal Biomechanical Properties on Rebound Tonometry (Icare200) and Applanation Tonometry (Perkins) Readings in Patients With Primary Congenital Glaucoma.

OBJECTIVE: The aim was to assess the influence of corneal biomechanics on intraocular pressure (IOP) measurements made with the Icare200 (IC200) rebound tonometer and the Perkins handheld applanation tonometer in patients with primary congenital glaucoma (PCG). MATERIALS AND METHODS: A total of 40 PCG patients and 40 healthy controls, age, and sex-matched, were recruited. IOP was measured with the Ocular Response Analyzer (IOPc, IOPg), IC200 and Perkins. The variables age, IOP, corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), best-corrected visual acuity, spherical equivalent, medications, and glaucoma surgeries were recorded for each subject. Univariate and multivariate analysis were used to detect effects of variables on IOP measurements. RESULTS: Mean CCT was 545.65±71.88 µm in PCG versus 558.78±27.58 µm in controls (P=0.284). CH and CRF were significantly lower in PCG group than in control group: mean CH 8.11±1.69 versus 11.15±1.63 mm Hg (P<0.001), and mean CRF 9.27±2.35 versus 10.71±1.75 mm Hg (P=0.002). Mean differences between IOP IC200-Perkins were 0.79±0.53 mm Hg in PCG versus 0.80±0.23 mm Hg in controls (P<0.001) and mean differences IC200-IOPc were -0.89±5.15 mm Hg in PCG (P<0.001) versus 1.60±3.03 mm Hg in controls (all P<0.009). Through multivariate analysis, CRF showed positive association and CH negative association with IOP measured with Perkins or IC200 in both subject groups. No association was detected for CCT, age, or sex. CONCLUSION: CH and CRF were identified as the main factors interfering with IOP measurements made with both tonometers in patients with PCG and healthy controls.