Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

[Research progress in the diagnosis and treatment of childhood glaucoma].

Childhood glaucoma is a disease that seriously endangers children's visual health. It will accompany the patients throughout their lives and bring a heavy burden to families and society. Most childhood blindness caused by glaucoma is preventable or treatable. Relevant research has made progress in recent years. Based on the new consensus reached by the World Glaucoma Association and the latest medical evidence at home and abroad, this article summarizes the definition, classification, diagnosis, molecular genetics, pathogenesis and comprehensive treatments including drugs and surgery of childhood glaucoma, with a focus on the application of various surgical methods, so as to provide reference for clinical and scientific research and improve the clinical diagnosis and treatment of childhood glaucoma.

Increasing the diagnostic yield of childhood glaucoma cases recruited into the 100,000 Genomes Project.

Childhood glaucoma (CG) encompasses a heterogeneous group of genetic eye disorders that is responsible for approximately 5% of childhood blindness worldwide. Understanding the molecular aetiology is key to improving diagnosis, prognosis and unlocking the potential for optimising clinical management. In this study, we investigated 86 CG cases from 78 unrelated families of diverse ethnic backgrounds, recruited into the Genomics England 100,000 Genomes Project (GE100KGP) rare disease cohort, to improve the genetic diagnostic yield. Using the Genomics England/Genomic Medicine Centres (GE/GMC) diagnostic pipeline, 13 unrelated families were solved (13/78, 17%). Further interrogation using an expanded gene panel yielded a molecular diagnosis in 7 more unrelated families (7/78, 9%). This analysis effectively raises the total number of solved CG families in the GE100KGP to 26% (20/78 families). Twenty-five percent (5/20) of the solved families had primary congenital glaucoma (PCG), while 75% (15/20) had secondary CG; 53% of this group had non-acquired ocular anomalies (including iris hypoplasia, megalocornea, ectopia pupillae, retinal dystrophy, and refractive errors) and 47% had non-acquired systemic diseases such as cardiac abnormalities, hearing impairment, and developmental delay. CYP1B1 was the most frequently implicated gene, accounting for 55% (11/20) of the solved families. We identified two novel likely pathogenic variants in the TEK gene, in addition to one novel pathogenic copy number variant (CNV) in FOXC1. Variants that passed undetected in the GE100KGP diagnostic pipeline were likely due to limitations of the tiering process, the use of smaller gene panels during analysis, and the prioritisation of coding SNVs and indels over larger structural variants, CNVs, and non-coding variants.

[Influence of corneal curvature and peripheral thickness on tonometry readings]. / Vliyanie krivizny i perifericheskoi tolshchiny rogovitsy na rezul'tat tonometrii.

PURPOSE: This study investigates the influence of peripheral corneal thickness (PCT) and its curvature on tonometry readings. MATERIAL AND METHODS: The study included 49 patients (49 eyes) who were indicated for glaucoma surgery. Using bidirectional applanation tonometry, the following parameters were obtained: IOPcc, IOPg - intraocular pressure (IOP) corrected for corneal compensation, taken as the most reliable indicator; IOP converted to Goldmann measurement, taken as the result of applanation tonometry, ΔIOP (IOPcc-IOPg), CH and CRF (corneal hysteresis and corneal resistance factor). During corneal topography, the corneal thickness was studied in the center, PCT at 1.5; 2, 3, 4 and 5 mm from the center in four meridians, as well as ΔPCT (PCT 3 mm - PCT 1.5 mm), the curvature of the anterior and posterior surfaces of the cornea and the depth of the anterior chamber. Aberrometry was used to obtain refractometry data and the curvature of the anterior surface of the cornea. The influence of the studied parameters on ΔIOP was evaluated. RESULTS: ΔIOP correlated with CRF (r= -0.652), CH (r= -0.873), central corneal thickness (r= -0.293), PCT at all distances except 5 mm (r= -0.297; -0.287; -0.302; -0.303), with the strong and weak meridians of the anterior surface of the cornea (r=0.328; r=0.315), with the strong and weak meridians of the posterior surface, as well as the average curvature of the posterior surface (r=0.307; r=0.332; r=0.328). After step-by-step selection of the above parameters for creating a linear regression model for ΔIOP calculation, CH, CRF and PCT1.5mm remained in the model. The model describes ΔIOP with high accuracy (R2=0.974). CONCLUSION: Biomechanical parameters of the cornea are the leading factor of applanation tonometry error. Individual linear dimensions of the cornea (thickness, curvature) have a lesser effect.

[Role of point-by-point light sensitivity in the assessment of glaucoma progression]. / Rol' potochechnoi svetochuvstvitel'nosti v otsenke progressirovaniya glaukomy.

PURPOSE: This study analyzes changes in light sensitivity in each test point of the visual field in patients with different stages of glaucoma. MATERIAL AND METHODS: The data of a prospective analytical case-control study were analyzed. All patients underwent assessment of retinal light sensitivity and its variability in 54 points corresponding to the 24-2 program. Mean light sensitivity values were calculated in each point. Intergroup analysis was performed to evaluate changes in light sensitivity in each point. RESULTS: The range of light sensitivity decrease in the early glaucoma group compared to the control group was from 1.5 to 3.6 dB. The range of light sensitivity decrease in the moderate glaucoma group compared to the control group was from 2.1 to 11.5 dB, and compared to the early glaucoma group - from -0.9 to 7.9 dB. The most frequent decrease in light sensitivity was detected in the nasal sector and along the horizontal line in the upper half of the visual field. This trend persisted within the central 10 degrees of the visual field. The range of light sensitivity decrease in the advanced glaucoma group compared to the control group was from 14.1 to 28.0 dB, and compared to the early glaucoma group - from 11.35 to 26.08 dB, compared to the moderate glaucoma group - from 9.1 to 23.5 dB. The most frequent and severe decrease in light sensitivity was detected in the paracentral zone in the lower half of the visual field. CONCLUSION: The study analyzed the trends in the development of glaucoma from the early to the advanced stage. The most frequent and severe defect in light sensitivity in cases of verified advanced glaucoma was found in the lower half of the visual field. Points No. 32, 33 and 40 can be indicated as the area of interest in assessing the progression of glaucoma, as they were found to have the most profound changes in light sensitivity as glaucoma progressed.

[Thresholds and variability of retinal light sensitivity in each point of the examined visual field]. / Porogovye znacheniya i variabel'nost' svetochuvstvitel'nosti setchatki v kazhdoi tochke issleduemogo polya zreniya.

PURPOSE: This study assesses the light sensitivity and its variability in each point of the visual field in patients without glaucoma and with different stages of glaucoma. MATERIAL AND METHODS: The data of a prospective analytical case-control study involving 500 patients were analyzed. The initial examination of all patients was performed using basic ophthalmological methods, including static perimetry. Retinal light sensitivity and its variability were assessed in 54 points corresponding to the Humphrey 24-2 program. Mean deviation and pattern standard deviation of light sensitivity were calculated for each point. RESULTS: The lowest light sensitivity values in patients with moderate glaucoma were found in the periphery of the nasal sector, at point No. 27 - 14.4 dB, and at points No. 24-26 along the horizontal axis from the nasal side - from 17.7 to 22.7 dB. The maximum variability of light sensitivity was found in the nasal sector on both sides of the horizontal line - from 10.7 to 11.5 dB. The average light sensitivity above the horizontal axis in patients with advanced glaucoma was 10.8 dB, which is 2 dB higher than in the lower half of the visual field - 8.8 dB. The highest light sensitivity values were found at points No. 24 - 17.7 dB and No. 31 - 16.78 dB, the lowest - at point No. 32 - 4.5 dB. The average variability values of light sensitivity in the upper half of the visual field were 9.6 dB, which is 1 dB less than in the lower half of the visual field - 10.6 dB. CONCLUSION: According to our data, points No. 32 and No. 40 are of particular interest in the diagnostic plan. In these loci, the highest light sensitivity values were determined in early and moderate glaucoma. However, the values in these points decrease significantly in advanced glaucoma. It can be assumed that changes in light sensitivity in these loci at the early stages of glaucoma may be a predictor of glaucoma progression.

Measuring Visual Fields in Children With Glaucoma Using a Portable Tablet.

Purpose: To compare perimetric outcomes of an iPad perimetry app (Melbourne Rapid Fields [MRF]) with those of the Humphrey Field Analyser (HFA) testing children with glaucoma. Methods: Sixteen children diagnosed and treated for glaucoma were recruited to evaluate their perimetric performance over two visits. At each visit, they undertook visual field assessment using the MRF application as well as the HFA. The HFA test was part of their usual clinical work up and a clinical assistant judged which test format (24-2 SITA standard or SITA fast) might be suited to the testing of that child. The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests, by way of regression, intraclass correlation coefficient and Bland-Altman analysis. Secondary measures were comparisons of pattern deviation indices, test times as well as an indication of participant test preference. Summary data show means ± standard deviation. Results: The age for our cohort was 7 to 15 years of age (mean, 10.0 ± 2.4 years of age). The MRF MD was in close concordance to HFA MD with an intraclass correlation coefficient of 0.91 (95% confidence interval, 0.82-0.95). Bland-Altman analysis found little bias (-0.6 dB) and a 95% coefficient of repeatability of 2.1 dB in eyes having a normal HFA MD. In eyes with glaucomatous visual field defects the 95% coefficient of repeatability at retest was much larger for both the MRF (10.5 dB) as well as for the HFA (10.0 dB). Average MRF test times (5.6 ± 1.2 minutes) were similar to SITA Fast (5.4 ± 1.9 minutes) with both being significantly faster than SITA standard (8.6 ± 1.4 minutes; P < 0.001). All children chose testing with the MRF as their preference. Conclusions: MRF correlated strongly with HFA and was preferred by the children over the HFA. MRF is suitable for perimetric evaluation of children with glaucoma. Translational Relevance: This study finds that an iPad based visual field test can be used with children having glaucoma to yield outcomes similar to SITA-fast. Children indicate a preference for such testing.

A hybrid framework for glaucoma detection through federated machine learning and deep learning models.

BACKGROUND: Glaucoma, the second leading cause of global blindness, demands timely detection due to its asymptomatic progression. This paper introduces an advanced computerized system, integrates Machine Learning (ML), convolutional neural networks (CNNs), and image processing for accurate glaucoma detection using medical imaging data, surpassing prior research efforts. METHOD: Developing a hybrid glaucoma detection framework using CNNs (ResNet50, VGG-16) and Random Forest. Models analyze pre-processed retinal images independently, and post-processing rules combine predictions for an overall glaucoma impact assessment. RESULT: The hybrid framework achieves a significant 95.41% accuracy, with precision and recall at 99.37% and 88.37%, respectively. The F1 score, balancing precision and recall, reaches a commendable 93.52%. These results highlight the robustness and effectiveness of the hybrid framework in accurate glaucoma diagnosis. CONCLUSION: In summary, our research presents an innovative hybrid framework combining CNNs and traditional ML models for glaucoma detection. Using ResNet50, VGG-16, and Random Forest in an ensemble approach yields remarkable accuracy, precision, recall, and F1 score. These results showcase the methodology's potential to enhance glaucoma diagnosis, emphasizing its promising role in early detection and preventing irreversible vision loss. The integration of ML and DNNs in medical imaging analysis suggests a valuable path for future advancements in ophthalmic healthcare.

Unilateral Glaucoma Without Facial Angioma in a Pediatric Patient: A Suspected Sturge-Weber Syndrome Variant.

The authors report a case of a 5-month-old full-term infant with chronic conjunctival redness and elevated intraocular pressure in the right eye. Magnetic resonance imaging ruled out leptomeningeal angiomatosis. Despite lacking a typical port-wine mark, the diagnosis of Sturge-Weber syndrome was established based on specific observations in the right eye that involved unilateral vascular glaucoma. These findings included Haab striae, a larger axial length measurement, an increased number of episcleral vessels with blood in Schlemm canal, and a thicker choroid in the macular region. This is the first reported pediatric case with these specific ocular manifestations in the absence of facial angioma, highlighting the need for awareness among clinicians to avoid misdiagnosis and facilitate proper management. [J Pediatr Ophthalmol Strabismus. 2024;61(3):e19-e22.].

Assessing the efficacy of 2D and 3D CNN algorithms in OCT-based glaucoma detection.

Glaucoma is a progressive neurodegenerative disease characterized by the gradual degeneration of retinal ganglion cells, leading to irreversible blindness worldwide. Therefore, timely and accurate diagnosis of glaucoma is crucial, enabling early intervention and facilitating effective disease management to mitigate further vision deterioration. The advent of optical coherence tomography (OCT) has marked a transformative era in ophthalmology, offering detailed visualization of the macula and optic nerve head (ONH) regions. In recent years, both 2D and 3D convolutional neural network (CNN) algorithms have been applied to OCT image analysis. While 2D CNNs rely on post-prediction aggregation of all B-scans within OCT volumes, 3D CNNs allow for direct glaucoma prediction from the OCT data. However, in the absence of extensively pre-trained 3D models, the comparative efficacy of 2D and 3D-CNN algorithms in detecting glaucoma from volumetric OCT images remains unclear. Therefore, this study explores the efficacy of glaucoma detection through volumetric OCT images using select state-of-the-art (SOTA) 2D-CNN models, 3D adaptations of these 2D-CNN models with specific weight transfer techniques, and a custom 5-layer 3D-CNN-Encoder algorithm. The performance across two distinct datasets is evaluated, each focusing on the macula and the ONH, to provide a comprehensive understanding of the models' capabilities in identifying glaucoma. Our findings demonstrate that the 2D-CNN algorithm consistently provided robust results compared to their 3D counterparts tested in this study for glaucoma detection, achieving AUC values of 0.960 and 0.943 for the macular and ONH OCT test images, respectively. Given the scarcity of pre-trained 3D models trained on extensive datasets, this comparative analysis underscores the overall utility of 2D and 3D-CNN algorithms in advancing glaucoma diagnostic systems in ophthalmology and highlights the potential of 2D algorithms for volumetric OCT image-based glaucoma detection.

The Effect of Yoga on Intraocular Pressure Using the "iCare HOME2" Tonometer.

BACKGROUND: Various yoga positions may have an unfavorable impact on intraocular pressure (IOP) and may therefore be seen as a potential risk factor for the progression of glaucoma. The new "iCare HOME2" is a handheld self-tonometer for IOP measurements outside clinical settings. This is the first study to evaluate the immediate effect of common yoga postures on the IOP of healthy and glaucomatous eyes using the "iCare HOME2" self-tonometer and to compare the time of IOP recovery in both groups. METHODS: This is a single-center, prospective, observational study including 25 healthy and 25 glaucoma patients performing the following yoga positions: "legs up" (Viparita Karani), "bend over" (Uttanasana), "plough pose" (Halasana), and the "down face dog" (Adho Mukha Svanasana) for 90 s each, with a 2-min break in between. IOP was measured with the "iCare HOME2" before, during, and after each position. RESULTS: IOP significantly increased in all eyes in all positions (p < 0.05), showing no statistically significant difference between healthy or glaucomatous eyes (p > 0.05). The mean rise in IOP in healthy subjects was 1.6 mmHg (SD 1.42; p = 0.037), 14.4 mmHg (SD 4.48; p < 0.001), 7.5 mmHg (SD 4.21; p < 0.001), and 16.5 mmHg (SD 3.71; p < 0.001), whereas in glaucoma patients, IOP rose by 2.8 mmHg (SD 2.8; p = 0.017), 11.6 mmHg (SD 3.86; p < 0.001), 6.0 mmHg (SD 2.24; p < 0.001), and 15.1 mmHg (SD 4.44; p < 0.001) during the above listed yoga positions, repsectively. The highest increase in IOP was seen in the down face position, reaching mean IOP values above 31 mmHg in both study groups. IOP elevation was observed immediately after assuming the yoga position, with no significant change during the following 90 s of holding each pose (p > 0.05). All IOP values returned to baseline level in all individuals, with no significant difference between healthy and glaucoma participants. CONCLUSION: Our data show that common yoga positions can lead to an acute IOP elevation of up to 31 mmHg in healthy as well as glaucoma eyes, with higher IOP values during head-down positions. Given that IOP peaks are a major risk factor for glaucomatous optic neuropathy, we generally advise glaucoma patients to carefully choose their yoga exercises. If and to what extent practicing yoga leads to glaucoma progression, however, remains unclear and warrants further research.

Case series: Superficial plexus en face may aid distinction of retinal nerve fiber layer loss from diabetic retinal ischemia versus glaucoma.

PURPOSE: This study aimed to demonstrate that the pattern and degree of capillary bed dropout in early glaucoma appear different on OCT-A superficial plexus en-face slabs compared with retinal ischemia. RNFL loss associated with retinal ischemia in diabetic patients may be explained and accounted for by overlying the RNFL deviation map on a superficial plexus en-face montage. CASE REPORTS: Three middle-aged White men with diabetes mellitus showed cup-to-disc ratios of approximately 0.7 and RNFL and ganglion thinning. Each patient had several Cirrus OCT and OCT-A scans taken of the posterior pole. The OCT-A en-face images demonstrated specific patterns of superficial capillary dropout. The appearance of superficial plexus capillary dropout in one case of glaucoma is contrasted against two cases of retinal ischemia. CONCLUSIONS: Early glaucoma appears to be associated with incomplete capillary bed dropout that extends from macular regions to the disc in a wedge- or arc-shaped pattern. Diabetic retinal ischemia appears to be associated with well-defined patchy and polygonal pockets of complete capillary bed obliteration that may not extend back to the disc. If an RNFL deviation map is superimposed over the superficial plexus en-face montage, areas of RNFL loss may correlate with and thus be well accounted for by areas of retinal ischemia in cases with RNFL thinning likely from ischemia. This approach may supplement inspection of OCT B-scans for focal retinal thinning when trying to differentiate RNFL and ganglion cell loss from retinal ischemia versus glaucoma in patients with diabetes. Formal research studies are needed to validate our observations and proposed use of OCT-A together with OCT in these patients.

Changes in corneal biomechanics in patients with glaucoma: a systematic review and meta-analysis.

INTRODUCTION: Corneal biomechanics has been implicated in a variety of ocular diseases. The purpose of this study was to evaluate the relationship between the glaucoma and corneal biomechanical properties, and exploring the value of corneal biomechanics in the diagnosis and follow-up of glaucoma diseases. METHODS: We searched studies in PubMed, EMBASE, Web of Science and clinicaltrials.gov., as of October 8, 2022. Only English studies were included, without publication time limit. We also searched the reference lists of published reviews. This meta-analysis was conducted with random-effects models, we used mean difference(MD) to evaluate the outcome, and the heterogeneity was assessed with the I2 statistic. Subgroup analyses were performed under the appearance of high heterogeneity. We used 11 items to describe the characteristics of included studies, publication bias was performed through the Egger's test. The quality assessment were evaluated by Newcastle-Ottawa Scale(NOS) items. RESULTS: A total of 27 eligible studies were identified for data synthesis and assessment. The result of meta-analysis showed that in the comparison of included indicators, the corneal biomechanics values of glaucoma patients were statistically lower than those of normal subjects in a similar age range. The covered indicators included central corneal thickness(CCT) (MD = -8.34, 95% CI: [-11.74, -4.94]; P < 0.001), corneal hysteresis(CH)(MD = -1.54, 95% CI: [-1.88, -1.20]; P < 0.001), corneal resistance factor(CRF)( MD = -0.82, 95% CI: [-1.21, -0.44]; P < 0.001), and intraocular pressure(IOP)( corneal-compensated intraocular pressure (IOPcc): MD = 2.45, 95% CI: [1.51, 3.38]; P < 0.001); Goldmann-correlated intraocular pressure (IOPg): MD = 1.30, 95% CI: [0.41, 2.20]; P = 0.004), they all showed statistical difference. While the value of axial length(AL) did not show statistically different(MD = 0.13, 95% CI: [-0.24, 0.50]; P = 0.48). CONCLUSION: Corneal biomechanics are associated with glaucoma. The findings can be useful for the design of glaucoma screening, treatment and prognosis.

Migraine headache and other risk factors associated with glaucoma among the adult population living in Armenia: a case-control study.

PURPOSE: This study aimed to assess the association between migraine headache and glaucoma among the adult population living in Armenia. METHODS: This case-control study recruited 145 cases with glaucoma and 250 controls without glaucoma and other ocular disorders except refractive error from Optomed Canada Diagnostic Eye Center in Armenia. A structured questionnaire contained questions on socio-demographics, family history of glaucoma and stroke, ocular health, smoking, migraine, and obstructive sleep apnea. The Migraine Screening Questionnaire assessed possible migraine and the Berlin Questionnaire measured obstructive sleep apnea. RESULTS: The mean ages of cases and controls were 63.3 (SD = 12.3) and 39.5 (SD = 13.5), respectively. Females comprised 62.8% of cases and 69.1% of controls. A total of 17.8% of cases and 19.0% of controls had possible migraine. In the adjusted analysis older age (OR 1.17; 95% CI 1.12; 1.23), average/lower than average socio-economic status (OR 5.27; 95% CI 1.30; 21.3), and family history of glaucoma (OR 4.25; 95% CI 1.51; 11.9) were associated with high-tension glaucoma. CONCLUSION: Timely case detection of glaucoma among those with average/low socio-economic status and those with family history of glaucoma could prevent further progression of the disease. Further studies to explore the relationship between migraine headache and specific types of glaucoma may be worthwhile.

Extraction of three-dimensional shapes in glaucoma patients in response to monocular depth cues.

PURPOSE: To assess the impact of glaucoma on perceiving three-dimensional (3D) shapes based on monocular depth cues. STUDY DESIGN: Clinical observational study. METHODS: Twenty glaucoma patients, subjected to binocular visual-field sensitivity (binocular-VFS) tests using a Humphrey Visual Field Analyzer, and 20 age-matched healthy volunteers, underwent two tasks: identifying the nearest vertex of a 3D shape using monocular shading (3D-SfS), texture (3D-SfT), or motion (3D-SfM) cues, and distinguishing elementary one-dimensional (1D) features of these cues. The association of the visual-field index (VFI) of binocular-VFS with 3D shape perception in glaucoma patients was also examined. RESULTS: Glaucoma patients demonstrated reduced accuracy in distinguishing 1D luminance brightness and a larger "error-in-depth" between the perceived and actual depths for 3D-SfM and 3D-SfS compared to healthy volunteers. Six glaucoma patients with a 100% VFI for binocular-VFS exhibited a similar error-in-depth to the other fourteen glaucoma patients; they had a larger error-in-depth for 3D-SfM compared to healthy volunteers. No correlation between the error-in-depth values and the VFI values of binocular-VFS was observed. CONCLUSIONS: The 3D shape perception in glaucoma patients varies based on the depth cue's characteristics. Impaired 1D discrimination and larger thresholds for 3D-SfM in glaucoma patients with a 100% VFI for binocular-VFS indicate more pronounced perceptual deficits of lower-level elementary features for 3D-SfS and higher-level visual processing of 3D shapes for 3D-SfM. The effects of the location and degree of binocular visual-field defects on 3D shape perception remain to be elucidated. Our research provides insights into the 3D shape extraction mechanism in glaucoma.

[Glaucoma Patient with Suspected Flammer Syndrome: Diagnostic Procedures and Therapeutic Implications]. / Glaukompatient mit Verdacht auf Flammer-Syndrom: diagnostische Schritte und therapeutische Konsequenzen.

If glaucoma damage develops despite normal intraocular pressure or if the damage progresses despite well-controlled intraocular pressure, we usually find other risk factors. One important group are the vascular factors. We should focus not only on the classical risk factors of atherosclerosis, such as arterial hypertension or dyslipidaemia, but also on dysregulation of blood flow, especially on primary vascular dysregulation (PVD). Low blood pressure, either current or in adolescence, low body mass index or frequently cold hands and feet may provide important hints. Very often PVD is coupled with a number of other symptoms and signs, and we then speak of a Flammer Syndrome (FS). If there is any indication of FS, we take a targeted patient history, undertake 24 h blood pressure monitoring, measure retinal venous pressure, and perform a dynamic retinal vessel analysis or nail fold capillary microscopy. This is especially recommended if the patient is relatively young or the damage is progressing rapidly. If the suspicion is confirmed, we then try to reduce the drops in blood pressure, lower the retinal venous pressure, improve the regulation of blood flow and reduce the oxidative stress in the mitochondria.

In Vivo Assessment of Retinal Phenotypes in Axenfeld-Rieger Syndrome.

Purpose: Axenfeld-Rieger syndrome (ARS) is characterized by ocular anomalies including posterior embryotoxon, iridocorneal adhesions, corectopia/iris hypoplasia, and developmental glaucoma. Although anterior segment defects and glaucoma contribute to decreased visual acuity, the role of potential posterior segment abnormalities has not been explored. We used high-resolution retinal imaging to test the hypothesis that individuals with ARS have posterior segment pathology. Methods: Three individuals with FOXC1-ARS and 10 with PITX2-ARS completed slit-lamp and fundus photography, optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscopy (AOSLO). Quantitative metrics were compared to previously published values for individuals with normal vision. Results: All individuals demonstrated typical anterior segment phenotypes. Average ganglion cell and inner plexiform layer thickness was lower in PITX2-ARS, consistent with the glaucoma history in this group. A novel phenotype of foveal hypoplasia was noted in 40% of individuals with PITX2-ARS (but none with FOXC1-ARS). Moreover, the depth and volume of the foveal pit were significantly lower in PITX2-ARS compared to normal controls, even excluding individuals with foveal hypoplasia. Analysis of known foveal hypoplasia genes failed to identify an alternative explanation. Foveal cone density was decreased in one individual with foveal hypoplasia and normal in six without foveal hypoplasia. Two individuals (one from each group) demonstrated non-foveal retinal irregularities with regions of photoreceptor anomalies on OCT and AOSLO. Conclusions: These findings implicate PITX2 in the development of the posterior segment, particularly the fovea, in humans. The identified posterior segment phenotypes may contribute to visual acuity deficits in individuals with PITX2-ARS.