Low-Grade Versus Medium-Grade Nuclear Sclerotic Cataract Density Produces Identical Surgical and Visual Outcomes: A Prospective Single-Surgeon Study

Purpose To determine whether the incidence of major complications and postoperative corrected distance visual acuity are comparable for surgery on low-grade versus medium-grade nuclear sclerotic cataracts. Design This was a prospective, consecutive, single-surgeon, no-exclusion study of 1025 cataract cases with one-month follow-up. Methods Patients were divided into two cohorts according to the nuclear sclerosis grade at presentation, as classified using the Lens Opacities Classification System (LOCS) III. Cohort A, representing low-grade nuclear sclerotic cataracts (grades 1-2), consisted of 739 eyes, while Cohort B, representing medium-grade nuclear sclerotic cataracts (grades 3-6), consisted of 286 eyes. Results There was no significant difference in major intraoperative or postoperative complications (p>0.999) between Cohorts A and B. The mean logMar preoperative corrected distance visual acuity (CDVA) in Cohort A was 0.245 as compared with 0.346 in Cohort B (p<0.001). There was no significant difference between cohorts for postoperative CDVA at one day (-0.168 versus -0.118; p=0.070), one week (-0.180 versus -0.147; p=0.405), or one month (-0.185 versus -0.161; p=0.569). Conclusions There was no significant difference in the incidence of operative complications or postoperative CDVA between the cohorts. These findings suggest that, in experienced hands, surgery for medium-grade nuclear sclerotic cataracts is equally effective and safe as compared with that for low-grade nuclear sclerotic cataracts

RVD: A Handheld Device-Based Fundus Video Dataset for Retinal Vessel Segmentation

Retinal vessel segmentation is generally grounded in image-based datasets collected with bench-top devices. The static images naturally lose the dynamic characteristics of retina fluctuation, resulting in diminished dataset richness, and the usage of bench-top devices further restricts dataset scalability due to its limited accessibility. Considering these limitations, we introduce the first video-based retinal dataset by employing handheld devices for data acquisition. The dataset comprises 635 smartphone-based fundus videos collected from four different clinics, involving 415 patients from 50 to 75 years old. It delivers comprehensive and precise annotations of retinal structures in both spatial and temporal dimensions, aiming to advance the landscape of vasculature segmentation. Specifically, the dataset provides three levels of spatial annotations: binary vessel masks for overall retinal structure delineation, general vein-artery masks for distinguishing the vein and artery, and fine-grained vein-artery masks for further characterizing the granularities of each artery and vein. In addition, the dataset offers temporal annotations that capture the vessel pulsation characteristics, assisting in detecting ocular diseases that require fine-grained recognition of hemodynamic fluctuation. In application, our dataset exhibits a significant domain shift with respect to data captured by bench-top devices, thus posing great challenges to existing methods. In the experiments, we provide evaluation metrics and benchmark results on our dataset, reflecting both the potential and challenges it offers for vessel segmentation tasks. We hope this challenging dataset would significantly contribute to the development of eye disease diagnosis and early prevention

An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity

Purpose: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. Design: Cross-sectional study. Participants: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients. Methods Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group. Main Outcome Measures: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. Results: A dose–response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1–2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). Conclusions: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members

Prevalence and type of artefact with spectral domain optical coherence tomography macular ganglion cell imaging in glaucoma surveillance

PURPOSE:The ganglion cell analysis (GCA) of the CIRRUSTM HD-OCT (Carl Zeiss, Meditec; Dublin, CA) provides measurement of the macular ganglion cell-inner plexiform layer (GCIPL) thickness. This study determined the frequency of scan artefacts and errors in GCIPL imaging in individuals undergoing HD-OCT surveillance for glaucoma. METHOD:A total of 1439 eyes from 721 subjects enrolled in a prospective study assessing predictors of glaucoma progression underwent macular GCIPL imaging with the CIRRUS HD-OCT at recruitment. The prevalence of acquisition errors, segmentation errors, and co-morbid macular pathology was determined. RESULTS:A total of 87 (6.0%) of the 1439 scans had either acquisition errors, segmentation artefacts, or other macular pathology. The most common co-morbid macular pathology was epiretinal membrane in 2.2% of eyes. CONCLUSION:The macular GCIPL scan was artefact free in 94% of eyes. However, epiretinal membrane and high myopia can cause scan artefact and should be considered when interpreting the results.Mona S. Awadalla, Jude Fitzgerald, Nicholas H. Andrew, Tiger Zhou, Henry Marshall, Ayub Qassim, Mark Hassall, Robert J. Casson, Stuart L. Graham, Paul R. Healey, Ashish Agar, Anna Galanopoulos, Simon Phipps, Angela Chappell, John Landers, Jamie E. Crai

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups

Pressure effects on neurons: investigations into the pathogenesis of glaucoma.

Cellular responses to changes in pressure are implicated in numerous disease processes. In glaucoma apoptosis of retinal ganglion cells (RGCs) is associated with elevated intra-ocular pressure (IOP), however the exact cellular basis of this link remains unclear. This research aimed to examine the direct response of neuronal cells to elevated hydrostatic pressure in terms of apoptosis. We developed an in vitro model consisting of a pressure chamber to adjust ambienthydrostatic pressure, a source of neuronal cells and methods to measure apoptosis in these cells. The neural cells examined were primary retinal cultures, four neuronal cell lines (B35, PC12, C17, NT2), and the RGC-5 cell line. Pressure conditions selected were within physiological limits; 100 mmHg above atmospheric pressure (as seen clinically in severe acute glaucoma) and extended in RGC-5 neurons to 30 mmHg (chronic glaucoma) and 15 mmHg (normal IOP). Apoptosis was detected by cell morphology and specific immunochemical markers: TUNEL and Annexin V. Caspase-3 activation, a known pathway of apoptosis, was also investigated in RGC-5 neurons. These fluorescent markers were detected and quantified by automated Laser Scanning Cytometry. Negative controls were treated identicallyexcept for the application of pressure, while positive controls were generated by treatment with a known apoptotic stimulus. The results showed that neurons responded to elevated hydrostatic pressure directly and that an apoptotic process was induced. There was a greater level of apoptosis in pressurised cells compared to the negative controls. This apoptotic effect at highpressures was seen in primary rat retinal cultures and in both undifferentiated (B35, C17, NT2, RGC-5) and differentiated (PC12, RGC-5) neuronal cell lines. RGC-5 neurons showed a graded response, proportionate to the level of pressure elevation, representative of the severity of analogous clinical settings (acute, chronic glaucoma & normal). RGC-5 neurons also showed increased activation of Capsase-3. Thus thispathway may play a role in pressure induced apoptosis. Our findings indicate that pressure alone may act as a stimulus for apoptosis inneuronal cells. We suggest the possibility of novel mechanisms of pressure relatedmechanotransduction and cell death, relevant to the pathogenesis of glaucoma

Glaucoma filtration surgery following sustained elevation of intraocular pressure secondary to intravitreal anti-VEGF injections

BACKGROUND AND OBJECTIVE: To document cases of sustained elevation of intraocular pressure (IOP) while receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents and subsequent management. PATIENTS AND METHODS: A retrospective series of all cases managed by the authors and colleagues was performed. RESULTS: Six patients developed sustained elevated IOP; five received ranibizumab and one bevacizumab. Four received unilateral and two received bilateral injections. Two had preexisting primary open-angle glaucoma and one had pseudoexfoliative glaucoma, all with stable IOP prior to anti-VEGF treatment. Angles were open in all cases. Peak IOP averaged 43 mm Hg (range: 34 to 60 mm Hg). The mean number of injections preceding the IOP increase was 10 (range: 1 to 20). Four patients required trabeculectomy, one selective laser trabeculoplasty, and one multiple topical medications. CONCLUSION: A sustained increase in IOP requiring glaucoma filtering surgery is a rare but important treatment complication for patients receiving intravitreal anti-VEGF therapy, especially those with preexisting glaucoma or glaucoma risk factors.7 page(s

Autonomous assessment of spontaneous retinal venous pulsations in fundus videos using a deep learning framework

Abstract The presence or absence of spontaneous retinal venous pulsations (SVP) provides clinically significant insight into the hemodynamic status of the optic nerve head. Reduced SVP amplitudes have been linked to increased intracranial pressure and glaucoma progression. Currently, monitoring for the presence or absence of SVPs is performed subjectively and is highly dependent on trained clinicians. In this study, we developed a novel end-to-end deep model, called U3D-Net, to objectively classify SVPs as present or absent based on retinal fundus videos. The U3D-Net architecture consists of two distinct modules: an optic disc localizer and a classifier. First, a fast attention recurrent residual U-Net model is applied as the optic disc localizer. Then, the localized optic discs are passed on to a deep convolutional network for SVP classification. We trained and tested various time-series classifiers including 3D Inception, 3D Dense-ResNet, 3D ResNet, Long-term Recurrent Convolutional Network, and ConvLSTM. The optic disc localizer achieved a dice score of 95% for locating the optic disc in 30 milliseconds. Amongst the different tested models, the 3D Inception model achieved an accuracy, sensitivity, and F1-Score of 84 ± 5%, 90 ± 8%, and 81 ± 6% respectively, outperforming the other tested models in classifying SVPs. To the best of our knowledge, this research is the first study that utilizes a deep neural network for an autonomous and objective classification of SVPs using retinal fundus videos

Cognitive Performance on the Montreal Cognitive Assessment Test and Retinal Structural and Functional Measures in Glaucoma

Background: Glaucoma, the leading cause of irreversible blindness, is classified as a neurodegenerative disease, and its incidence increases with age. Pathophysiological changes, such as the deposition of amyloid-beta plaques in the retinal ganglion cell layer, as well as neuropsychological changes, including cognitive decline, have been reported in glaucoma. However, the association between cognitive ability and retinal functional and structural measures in glaucoma, particularly glaucoma subtypes, has not been studied. We studied the association between cognitive ability and the visual field reliability indices as well as the retinal ganglion cell (RGC) count estimates in a cohort of glaucoma patients. Methods: A total of 95 eyes from 61 glaucoma patients were included. From these, 20 were normal-tension glaucoma (NTG), 25 were primary open-angle glaucoma (POAG), and 16 were glaucoma suspects. All the participants had a computerised Humphrey visual field (HVF) assessment and optical coherence tomography (OCT) scan and were administered the written Montreal Cognitive Assessment (MoCA) test. RGC count estimates were derived based on established formulas using the HVF and OCT results. A MoCA cut-off score of 25 and less was designated as cognitive impairment. Student&rsquo;s t-test was used to assess differences between the groups. The Pearson correlation coefficient was used to assess the association between MoCA scores and retinal structural and functional measures. Results: Significant associations were found between MoCA scores and the false-negative and pattern standard deviation indices recorded on the HVF (r = &minus;0.19, r = &minus;0.22, p &lt; 0.05). The mean IOP was significantly lower in the cognitively impaired group (i.e., MOCA &le; 25) (13.7 &plusmn; 3.6 vs. 15.7 &plusmn; 4.5, p &lt; 0.05). No significant association was found between RGC count estimates and MoCA scores. Analysis of these parameters in individual glaucoma subtypes did not reveal any group-specific significant associations either

Baseline data of patients enrolled in PROGRESSA study : glaucoma suspect and early manifest glaucoma progression trial

1 page(s