Differential Gene and Protein Expression of Conjunctival Bleb Hyperfibrosis in Early Failure of Glaucoma Surgery.

The early failure of glaucoma surgery is mainly caused by over-fibrosis at the subconjunctival space, causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients who re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signatures with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGFA, CXCL8, MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGFA and IL8 protein levels were also increased in fibroblast supernatants. We propose that an increase in these proteins could be useful in detecting conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery, leading to more optimal and personalized treatments.

Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients.

Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP), and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). A total of 57 (41%) eyes were under three or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. The mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg, respectively. Significant differences in tIOP were found between heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) (p = 0.031). The MD values presented significant differences between wildtype rs3766355 (-2 ± 2.2 dB), HT (-3.87 ± 4 dB), and HM carriers (-9.37 ± 9.51 dB) (p = 0.009). Significant differences were also observed between the MD in wildtype rs3753380 (-6.1 ± 8.67 dB), HT (-9.02 ± 8.63 dB), and HM carriers (-9.51 ± 7.44 dB) (p = 0.017). Patients carrying the variant rs3766355 in HM or HT presented clinically-significantly higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, and the more alleles that were affected, the worse the MD value, meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.

Effect of nepafenac on the foveal profile of glaucomatous patients undergoing phacoemulsification.

PURPOSE: Retrospective, pilot study to determine whether nepafenac treatment pre- and postcataract surgery in glaucoma patients using topical hypotensive agents minimized cystoid macular edema by comparing pre- and postsurgical foveal characteristics, as in some cases these agents cannot be withdrawn and, hypothetically, their inflammatory effect on the fovea could be neutralized by the addition of nepafenac. METHODS: Patients were divided into two subgroups depending on whether or not topical nepafenac was added to the surgical protocol (NEP = nepafenac group and nNEP = non nepafenac group). All had undergone phacoemulsification and data on pre- and postoperative macular status were recorded. RESULTS: In the nNEP group, there was a significant increase in foveal thickness (FT) in the first month postoperative visit with respect to the preoperative status (p = 0.006), and this situation did not change at the third postoperative month (p = 0.9411). In the NEP group, the increase in FT was not significant at the first month after surgery (p = 0.056) nor at the final visit (p = 0.268), in contrast to the nNEP group. CONCLUSION: This study of the possible prophylactic effect of nepafenac on postoperative macular edema supports the results of other studies that confirm subclinical edema post phacoemulsification, and found a significantly lower gradient in the increase in FT in patients treated pre- and postoperatively with nepafenac.

Classifying glaucoma exclusively with OCT: comparison of three clustering algorithms derived from machine learning.

BACKGROUND/AIMS: To objectively classify eyes as either healthy or glaucoma based exclusively on data provided by peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform (GCIPL) measurements derived from spectral-domain optical coherence tomography (SD-OCT) using machine learning algorithms. METHODS: Three clustering methods (k-means, hierarchical cluster analysis -HCA- and model-based clustering-MBC-) were used separately to classify a training sample of 109 eyes as either healthy or glaucomatous using solely 13 SD-OCT parameters: pRNFL average and sector thicknesses and GCIPL average and minimum values together with the six macular wedge-shaped regions. Then, the best-performing algorithm was applied to an independent test sample of 102 eyes to derive close estimates of its actual performance (external validation). RESULTS: In the training sample, accuracy was 91.7% for MBC, 81.7% for k-means and 78.9% for HCA (p value = 0.02). The best MBC model was that in which subgroups were allowed to have variable volume and shape and equal orientation. The MBC algorithm in the independent test sample correctly classified 98 out of 102 cases for an overall accuracy of 96.1% (95% CI, 92.3-99.8%), with a sensitivity of 94.3 and 100% specificity. The accuracy for pRNFL was 92.2% (95% CI, 86.9-97.4%) and for GCIPL 98.0% (95% CI, 95.3-100%). CONCLUSIONS: Clustering algorithms in general (and MBC in particular) seem promising methods to help discriminate between healthy and glaucomatous eyes using exclusively SD-OCT-derived parameters. Understanding the relative merits of one method over others may also provide insights into the nature of the disease.

Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a complex disease with a strong hereditably component. Several genetic variants have recently been associated with POAG, partially due to technological improvements such as next-generation sequencing (NGS). The aim of this study was to genetically analyze patients with POAG to determine the contribution of rare variants and hypomorphic alleles associated with glaucoma as a future method of diagnosis and early treatment. Seventy-two genes potentially associated with adult glaucoma were studied in 61 patients with POAG. Additionally, we sequenced the coding sequence of CYP1B1 gene in 13 independent patients to deep analyze the potential association of hypomorphic CYP1B1 alleles in the pathogenesis of POAG. We detected nine rare variants in 16% of POAG patients studied by NGS. Those rare variants are located in CYP1B1, SIX6, CARD10, MFN1, OPTC, OPTN, and WDR36 glaucoma-related genes. Hypomorphic variants in CYP1B1 and SIX6 genes have been identified in 8% of the total POAG patient assessed. Our findings suggest that NGS could be a valuable tool to clarify the impact of genetic component on adult glaucoma. However, in order to demonstrate the contribution of these rare variants and hypomorphic alleles to glaucoma, segregation and functional studies would be necessary. The identification of new variants and hypomorphic alleles in glaucoma patients will help to configure the genetic identity of these patients, in order to make an early and precise molecular diagnosis.

Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population.

PURPOSE: To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). METHODS: Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. RESULTS: We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). CONCLUSIONS: The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1.

Surgical Repair of the Extrusion of the Body of a PAUL Implant for Glaucoma.

The purpose of our article was to describe a simple but effective surgical technique performed on a patient with an extrusion of part of the body of a PAUL drainage implant for glaucoma. We present the case of a patient with refractory glaucoma and a history of multiple ocular interventions. A PAUL shunt was implanted and in the early postoperative period the patient presented extrusion of part of the implant body. An excessive scarring tissue at the lateral rectus muscle tendon hampered the placement of the lateral wing under the muscle; therefore, we decided to trim a part of it and suture the implant body to the sclera. The surgical technique that satisfactorily resolved the complication is described and shown in a video. This is the first time that such complication is described with the PAUL implant. We suggest that the intrinsic characteristics of the implant, mainly the dimensions, material, and thickness, made it possible for a potentially serious complication such as that described to be solved in a relatively simple and nontraumatic way for the eye.

External Validation and Clinical Applicability of Two Optical Coherence Tomography-Based Risk Calculators for Detecting Glaucoma.

Purpose: To clinically validate the diagnostic ability of two optical coherence tomography (OCT)-based glaucoma diagnostic calculators (GDCs). Methods: We conducted a retrospective, consecutive sampling of 76 patients with primary open-angle glaucoma, 107 glaucoma suspects, and 67 controls. Demographics, reliable visual field testing, and macular and optic disc OCT were collected. The reference diagnosis was compared against the probability of having glaucoma obtained from two GDCs derived from multivariate logistic regressions using quantitative and qualitative (GDC1) or only quantitative (GDC2) OCT data. The discrimination (area under the curve [AUC]) and calibration (calibration plots) were compared for both calculators and the best OCT parameters. Results: GDC2 was able to identify 46.9% more suspects and 14.7% more glaucomatous eyes than GDC1. Both GDCs obtained the highest discriminative ability in glaucomatous eyes (GDC1 AUC = 0.949; GDC2 = 0.943 vs inferior peripapillary retinal nerve fiber layer [pRNFL] = 0.931; P = 0.43). The discriminating ability was not as good for glaucoma suspects, but the GDCs were not inferior to pRNFL (GDC 1 AUC = 0.739; GDC2 = 0.730; inferior pRNFL = 0.760; P = 0.54) and GDC2 was still able to correctly identify up to 30.8% more cases than the conventional OCT classification. Calibration showed risk underestimation for both groups and calculators, but it was better in GDC2 and in patients with glaucoma. Conclusions: OCT-based calculators showed an excellent diagnostic performance in glaucomatous eyes. GDC2 was able to identify approximately 30% more cases than the conventional pRNFL inferior OCT classification in both groups, suggesting a potential role of these composite scores in clinical practice. Translational Relevance: These OCT-based calculators may improve glaucoma diagnosis in clinical care.

Impact of Systemic Comorbidities on Ocular Hypertension and Open-Angle Glaucoma, in a Population from Spain and Portugal.

Open-angle glaucoma (OAG), the most prevalent clinical type of glaucoma, is still the main cause of irreversible blindness worldwide. OAG is a neurodegenerative illness for which the most important risk factor is elevated intraocular pressure (IOP). Many questions remain unanswered about OAG, such as whether nutritional or toxic habits, other personal characteristics, and/or systemic diseases influence the course of glaucoma. As such, in this study, we performed a multicenter analytical, observational, case-control study of 412 participants of both sexes, aged 40-80 years, that were classified as having ocular hypertension (OHT) or OAG. Our primary endpoint was to investigate the relationship between specific lifestyle habits; anthropometric and endocrine-metabolic, cardiovascular, and respiratory events; and commonly used psychochemicals, with the presence of OHT or OAG in an ophthalmologic population from Spain and Portugal. Demographic, epidemiological, and ocular/systemic clinical data were recorded from all participants. Data were analyzed using the R Statistics v4.1.2 and RStudio v2021.09.1 programs. The mean age was 62 ± 15 years, with 67-80 years old comprising the largest subgroup sample of participants in both study groups. The central corneal thickness (ultrasound pachymetry)-adjusted IOP (Goldman tonometry) in each eye was 20.46 ± 2.35 and 20.1 ± 2.73 mmHg for the OHT individuals, and 15.8 ± 3.83 and 16.94 ± 3.86 mmHg for the OAG patients, with significant differences between groups (both p = 0.001). The highest prevalence of the surveyed characteristics in both groups was for overweight/obesity and daily coffee consumption, followed by psychochemical drug intake, migraine, and peripheral vasospasm. Our data show that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from OHT to OAG in this Spanish and Portuguese population.

Risk Factors for Failure in Double-Plate Tube Surgery for Refractory Glaucoma: 25 Years Surgical Experience.

PURPOSE: To investigate risk factors associated with success and failure in double-plate tube surgery. METHODS: This retrospective case-series observational study included 243 consecutive eyes that underwent anterior-segment double-plate tube surgery from 1990 to 2015. Evaluation of the efficacy of the device was based on the final intraocular pressure (IOP) and the need for anti-glaucoma medication. We also assessed success and failure according to risk factors for trabeculectomy and an early hypertensive phase (HP). RESULTS: Preoperative IOP was 37.3±13.1 mmHg (mean±SD) with 3.0±0.7 medications. After a median follow-up of 44.3 months, the mean IOP was 14.6±6.3 mmHg with 0.4±1.0 medications. The final IOPs ranged from 6 to 21 mmHg in 87.24% of eyes; however, 25.47% required medication. No risk factors studied were associated with surgical failure. Preoperative IOP, glaucoma type, previous surgery, previous anti-glaucoma drugs, implant type, and HP were associated with partial success (p<0.05). HP and preoperative use of brimonidine reduced the probability of complete success by 66.9% and 68.2%, respectively (p<0.05). HP was more likely when chronic preoperative prostaglandin analogues were administered (odds ratio [OR] 4.286; 95% confidence intervals [CI] 1.593-11.529; P=0.0039) and when the tube was located in the posterior chamber (OR 3.561; 95% CI 1.286-9.861; P=0.0145). CONCLUSION: Tube surgery is effective and seems to be independent of the major risk factors for glaucoma surgery. However, previous surgery and some chronic preoperative drugs are related to the need for glaucoma medication to achieve the target pressure.

Hemorrhagic Descemet's Membrane Detachment in Nonpenetrating Glaucoma Surgery.

PURPOSE: To describe 5 representative cases of hemorrhagic Descemet's membrane (DM) detachment in glaucoma surgery that had different origins, mechanisms and treatments. METHODS: Clinical records of patients that had undergone a nonpenetrating glaucoma surgery, with a diagnosis of hemorrhagic DM detachment were reviewed for demographic data, clinical findings and treatment applied. RESULTS: Five patients with hemorrhagic DM detachment were included in this case series. They all had different causes, namely a massive hemorrhage at the end of a canaloplasty procedure, a needling maneuver, autologous blood injection, Swan syndrome, and frequent eye rubbing. Hematoma evacuation was performed in 4 eyes, 1 of them from under the scleral flap of the deep sclerectomy and 3 of them through a surgical or laser perforation in DM. Air tamponade was done in most of these cases. One of these cases required transcorneal suture fixation. One case was observed expectantly. All cases successfully recovered but peripheral corneal stain was persistent in 2 cases. CONCLUSION: Hemorrhagic DM detachment is a rare but potential vision-threatening complication in glaucoma surgery. Different mechanisms may cause the bleeding and there are several techniques available to approach this complication. Pre-Descemet hematoma should be drained to avoid permanent corneal stain and air/gas tamponade may help to prevent recurrences.

Clinical Study of the IOPTx™ System - an Electroceutical Wearable to Lower Intraocular Pressure.

Purpose: To investigate the safety and efficacy of the IOPTx™ system - a novel wearable, electroceutical treatment to lower intraocular pressure. Methods: Patients wear the customized contact lens and spectacles of the IOPTx™ system and undergo three 15-minute randomized stimulation trials at different stimulus amplitudes with 15 minutes of rest in between. The parameters for the stimulation trials include a frequency of 50 Hz, a pulse width of 100 µs, and current amplitudes between 90-150 µA. The optometrist measures the intraocular pressure (IOP) before, immediately after, and 15 minutes after the trial, and performs topography, a slit eye examination, and specular microscopy before and after the entire study to check the health of the eye and confirm the safety of the system. Results: The IOPTx™ system successfully modulates a patient's IOP. By testing various currents, we create individual tuning curves examining the effect of the stimulation amplitude on the change in IOP. Each patient may have an optimal dose-response curve and by normalizing to this value, the IOPTx™ system decreased IOP by an average of 17.7% with fifteen minutes of therapy. No Adverse Events or Adverse Device Effects occurred.Conclusions: The results of this clinical case series provide preliminary evidence of efficacy and safety of the IOPTx™ system and its potential usefulness to lower IOP in glaucoma and ocular hypertension.

Effect of CPAP Therapy on 24-Hour Intraocular Pressure-Related Pattern From Contact Lens Sensors in Obstructive Sleep Apnea Syndrome.

Purpose: To evaluate the effect of continuous positive airway pressure (CPAP) therapy on 24-hour intraocular pressure (IOP)-related pattern from contact lens sensors (CLS) in obstructive sleep apnea syndrome (OSAS). Methods: Prospective, observational, case series study. Twenty-two eyes of 22 newly diagnosed patients with severe OSAS were included. A first 24-hour CLS measurement was performed before CPAP therapy was started, and a second 24-hour CLS monitoring was performed after beginning CPAP. We analyzed the amplitude and the maximum and minimum IOP-related values (m Veq). We also analyzed IOP-related measurements at five-minute intervals throughout the first hour of nocturnal acrophase, starting from when the patient fell asleep. Results: The baseline measurements showed significant fluctuations in the IOP, with the highest IOP readings being recorded at night (nocturnal acrophase) in 17 of 22 patients (77.27%). Nocturnal acrophase began when the patients laid down to sleep. During CPAP therapy, the patients showed a more marked increase in IOP in the initial phase of nocturnal acrophase, with significant differences at 20, 25, 30, and 55 minutes (P < 0.05). Conclusions: Most of patients with severe OSAS exhibited a nocturnal acrophase and the highest IOP readings at night. CPAP was associated with additional increase in IOP-related pattern for at least the first hour of CPAP use. Translational Relevance: Our results suggest that CPAP was associated with additional increase in IOP during the initial phase of nocturnal acrophase. This effect could be important in the management of patients with OSAS and glaucomatous progression.

XEN45 real-life evaluation: Survival analysis with bleb needling and major revision outcomes.

PURPOSE: To evaluate real-life outcomes of XEN45 stent surgery including bleb needling (BN) and surgical bleb revision (SBR). METHODS: Retrospective analysis of all XEN45 gel stents implanted in a tertiary glaucoma center with a minimum follow-up of 6 months. The main outcomes were intraocular pressure (IOP), the number of glaucoma medications, postoperative maneuvers like BN, and subsequent SBR. Success was defined as IOP ⩽ 18 and 20% reduction (criterion A), ⩽15 and 25% reduction (criterion B), and ⩽12 mmHg and 30% reduction (criterion C) reached with (qualified) or without (complete) medications at the last visit. Complete failure was defined as additional glaucoma surgery, loss of light perception, or sight-threatening complications. Multivariable Cox regression and Kaplan-Meier survival estimates tests were performed. RESULTS: Fifty-eight eyes with either stand-alone or combined Phaco-XEN surgery were included. Complete success by the different definitions was 50.0% (95% confidence interval, 5.8%-84.5%) (A), 50.0% (5.8%-84.5%) (B), and 25% (0.9%-66.5%) (C) whereas qualified success was 38.3% (1.6%-80.1%), 31.7% (2.0%-71.4%), and 0%, respectively, at the 24-months visit. 30% of cases underwent BN with 5-Fluorouracil, and SBR was performed in 17.5% of eyes. Low IOP levels at 1-month and early BN were significantly associated with success. The highest chance of failure was achieved in the combined Phaco-XEN group undergoing SBR. CONCLUSIONS: In our real-life setting, the first month IOP was associated with greater success rates. Although BN obtained improved IOP values, SBR was associated with a greater bleb survival in the stand-alone XEN group. Both BN and SBR had poor outcomes in the combined Phaco-XEN group.

Surgical Approach and Outcomes of Uveitic Glaucoma in a Tertiary Hospital.

AIM AND OBJECTIVE: This study aimed to evaluate the performance of and indication for different surgical techniques in the management of uveitic glaucoma (UG). MATERIALS AND METHODS: A retrospective audit of records of all patients with UG who underwent ≥1 glaucoma surgery, between January 2007 and December 2016. The main outcomes were intraocular pressure (IOP) and the need for antihypertensive medication at each follow-up visit. The total number of surgical interventions needed to control IOP was recorded. Postoperative interventions and complications were analyzed. RESULTS: Forty eyes from 34 patients were assessed. Overall, baseline IOP was 30.7 ± 8.2 mm Hg, and postoperative mean IOP at the last visit was 16.4 ± 2.0 mm Hg, with a mean follow-up of 28 months. Antihypertensive medications were reduced from 2.8 ± 0.8 to 0.8 ± 1.2. During the follow-up, 61.8% of the eyes required only one glaucoma surgery. There was no correlation between the location of uveitis and the total number of glaucoma surgeries required. The greatest IOP reductions were in cases treated with non-penetrating deep sclerectomy (21%), Ahmed valve (23%), and cyclophotocoagulation (CPC) (51%); in cases where an Ahmed implant was the first surgical option, a 43% reduction was achieved. CONCLUSION: Filtering procedures, glaucoma drainage devices, and CPC are all good options for IOP control in UG, but all are prone to failure over time. With respect to IOP reduction, the safety profile, and postoperative care, Ahmed implants and CPC might be the best first surgical option. CLINICAL SIGNIFICANCE: The article highlights the versatility of the surgical techniques required to treat UG, which is one of the most difficult types of glaucoma to manage. HOW TO CITE THIS ARTICLE: Ventura-Abreu N, Mendes-Pereira J, Pazos M, et al. Surgical Approach and Outcomes of Uveitic Glaucoma in a Tertiary Hospital. J Curr Glaucoma Pract 2021;15(2):52-57.

SD-OCT peripapillary nerve fibre layer and ganglion cell complex parameters in glaucoma: principal component analysis.

BACKGROUND/AIMS: To identify objective glaucoma-related structural features based on peripapillary (p) and macular (m) spectral domain optical coherence tomography (SD-OCT) parameters and assess their discriminative ability between healthy and glaucoma patients. METHODS: Two hundred and sixty eyes (91 controls and 169 glaucoma) were included in this prospective study. After a complete examination, all participants underwent the posterior pole and the peripapillary retinal nerve fibre layer (pRNFL) protocols of the Spectralis SD-OCT. Principal component analysis (PCA), a data reduction method, was applied to identify and characterise the main information provided by the ganglion cell complex (GCC). The discriminative ability between healthy and glaucomatous eyes of the first principal components (PCs) was compared with that of conventional SD-OCT parameters (pRNFL, macular RNFL (mRNFL), macular ganglion cell layer (mGCL)and macular inner plexiform layer (mIPL)) using 10-fold cross-validated areas under the curve (AUC). RESULTS: The first PC explained 58% of the total information contained in the GCC and the pRNFL parameters and was the result of a general combination of almost all variables studied (diffuse distribution). Other PCs were driven mainly by pRNFL and mRNFL measurements. PCs and pRNFL had similar AUC (0.95 vs 0.96, p=0.88), and outperformed the other structural measurements: mRNFL (0.91, p=0.002), mGCL (0.92, p=0.02) and mIPL (0.92, p=0.0001). CONCLUSIONS: PCA identified a diffuse representation of the papillary and macular SD-OCT parameters as the most important PC to summarise structural data in healthy and glaucomatous eyes. PCs and pRNFL parameters showed the greatest discriminative ability between healthy and glaucoma cases.

Multimodal retinal imaging of familial amyloid polyneuropathy.

Background: Retinal amyloid angiopathy is a sight-threatening complication of familial amyloid polyneuropathy (FAP) caused by pathological deposition of transthyretin. The purpose of this report is to present ocular findings in patients with FAP using a combination of novel non-invasive retinal imaging techniques, including first time published images of optical coherence tomography angiography (OCT-A) in FAP.Materials and methods: Observational cross-sectional study of retinal images in patients with FAP using: fundus ultra wide-field photography (UWF); autofluorescence (AF); optical coherence tomography (OCT); and, OCT-A. Fifteen eyes of eight patients with FAP from a tertiary center were included. A descriptive analysis of obtained images and clinical data was performed.Results: Amyloid vitreous and retinal deposits were easily identified using OCT scans, AF, and UWF images, especially in the red-free modality. OCT-A allowed quality reconstruction of posterior pole vasculature, foveal avascular zone, and areas of ischemia.Conclusions: Different modalities of currently available non-invasive retinal imaging techniques, including OCT-A scans described for the first time in FAP, are safe and useful in detecting and analyzing retinal amyloidosis. Retinopathy in FAP in the studied group was more frequent than previously reported.

Novel LMX1B mutation in familial nail-patella syndrome with variable expression of open angle glaucoma.

PURPOSE: To describe the genetic and clinical findings in a large Spanish pedigree with nail-patella syndrome (NPS) and to investigate the expressivity of open angle glaucoma (OAG) in the family members. METHODS: All individuals underwent a complete ophthalmologic examination, including optical coherence tomography (OCT) of the optic disc and peripapillary region and ultrasound pachymetry. Screening for mutations in the LMX1B gene was performed by denaturing gradient gel electrophoresis and direct genomic sequencing analysis. RESULTS: Ten family members had NPS, seven with varying degrees of ocular hypertension (OHT). Only one of these had advanced OAG. The others showed high pachymetry values and OCT retinal nerve fiber layer (RNFL) thickness above the normal values. Screening for mutations in the exonic and flanking sequences of the LMX1B gene showed a deletion of one G (289delG) within the coding sequence of exon 3 at codon 97, resulting in a frame shift that creates a premature stop at codon 105 (E97fsX105), predicting a truncated protein. This mutation was present in all NPS patients and absent in the unaffected family members. CONCLUSIONS: A novel mutation in the homeobox transcription factor LMX1B causes NPS in a family with variable expressivity of the syndrome, including OAG. The pathogenic mechanism resulting from the mutation is presumably haploinsufficiency rather than a dominant negative effect, which would explain the clinical variability in this family. All NPS OHT patients had considerably thick corneas and RNFL.

Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort.

INTRODUCTION: The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. DESIGN: Retrospective, observational, multicentre, cohort study. MATERIAL AND METHODS: The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. RESULTS: 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. CONCLUSIONS: The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment.

Persistent Hypotony Associated with Immunosuppressive Therapy in Glaucoma Drainage Implant Surgery.

PURPOSE: To describe the histopathology of non-valved implant capsules in three cases of persistent postoperative hypotony after the restrictive tube ligature was released in patients receiving immunosuppressive therapy. OBSERVATIONS: The macroscopic appearance of the capsules 3 and 4 months postoperatively was immature and loose. Microscopic examination disclosed extremely irregular thin tissue, with thicknesses ranging from 0.02 to 0.6 mm, depending on the capsular location studied. Withdrawal of immunosuppressive therapy did not facilitate rebuilding of new capsules. Replacement with a valved implant device was necessary in two cases; the third case recovered with tapering of prednisone. CONCLUSIONS AND IMPORTANCE: The use of chronic systemic immunosuppressive therapy might interfere with capsular formation around the plates of drainage devices inducing persistent hypotony. In these cases, the use of valved implants might be safer.