Developing a privacy-preserving deep learning model for glaucoma detection: a multicentre study with federated learning.

BACKGROUND: Deep learning (DL) is promising to detect glaucoma. However, patients' privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images. METHODS: This is a multicentre study. The FL paradigm consisted of a 'central server' and seven eye centres in Hong Kong, the USA and Singapore. Each centre first trained a model locally with its own OCT optic disc volumetric dataset and then uploaded its model parameters to the central server. The central server used FedProx algorithm to aggregate all centres' model parameters. Subsequently, the aggregated parameters are redistributed to each centre for its local model optimisation. We experimented with three three-dimensional (3D) networks to evaluate the stabilities of the FL paradigm. Lastly, we tested the FL model on two prospectively collected unseen datasets. RESULTS: We used 9326 volumetric OCT scans from 2785 subjects. The FL model performed consistently well with different networks in 7 centres (accuracies 78.3%-98.5%, 75.9%-97.0%, and 78.3%-97.5%, respectively) and stably in the 2 unseen datasets (accuracies 84.8%-87.7%, 81.3%-84.8%, and 86.0%-87.8%, respectively). The FL model achieved non-inferior performance in classifying glaucoma compared with the traditional model and significantly outperformed the individual models. CONCLUSION: The 3D FL model could leverage all the datasets and achieve generalisable performance, without data exchange across centres. This study demonstrated an OCT-based FL paradigm for glaucoma identification with ensured patient privacy and data security, charting another course toward the real-world transition of artificial intelligence in ophthalmology.

Risk of Normal Tension Glaucoma Progression From Automated Baseline Retinal-Vessel Caliber Analysis: A Prospective Cohort Study.

PURPOSE: To determine the relationship between baseline retinal-vessel calibers computed by a deep-learning system and the risk of normal tension glaucoma (NTG) progression. DESIGN: Prospective cohort study. METHODS: Three hundred and ninety eyes from 197 patients with NTG were followed up for at least 24 months. Retinal-vessel calibers (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]) were computed from fundus photographs at baseline using a previously validated deep-learning system. Retinal nerve fiber layer (RNFL) thickness and visual field (VF) were evaluated semiannually. The Cox proportional-hazards model was used to evaluate the relationship of baseline retinal-vessel calibers to the risk of glaucoma progression. RESULTS: Over a mean follow-up period of 34.36 ± 5.88 months, 69 NTG eyes (17.69%) developed progressive RNFL thinning and 22 eyes (5.64%) developed VF deterioration. In the multivariable Cox regression analysis adjusting for age, gender, intraocular pressure, mean ocular perfusion pressure, systolic blood pressure, axial length, standard automated perimetry mean deviation, and RNFL thickness, narrower baseline CRAE (hazard ratio per SD decrease [95% confidence interval], 1.36 [1.01-1.82]) and CRVE (1.35 [1.01-1.80]) were associated with progressive RNFL thinning and narrower baseline CRAE (1.98 [1.17-3.35]) was associated with VF deterioration. CONCLUSION: In this study, each SD decrease in the baseline CRAE or CRVE was associated with a more than 30% increase in the risk of progressive RNFL thinning and a more than 90% increase in the risk of VF deterioration during the follow-up period. Baseline attenuation of retinal vasculature in NTG eyes was associated with subsequent glaucoma progression. High-throughput deep-learning-based retinal vasculature analysis demonstrated its clinical utility for NTG risk assessment.

Combined Phacoemulsification-Endoscopic Cyclophotocoagulation versus Phacoemulsification Alone in Primary Angle-Closure Glaucoma: A Pilot Randomized Controlled Trial.

PURPOSE: To compare combined phacoemulsification plus endoscopic cyclophotocoagulation (ECP) versus phacoemulsification alone in primary angle-closure glaucoma (PACG) with coexisting cataract. DESIGN: Prospective randomized controlled clinical trial-a pilot study. PARTICIPANTS: Forty-eight PACG eyes of 48 patients with coexisting cataract. INTERVENTION: Recruited patients were randomized into undergoing phacoemulsification plus ECP or phacoemulsification alone. After surgery, patients were followed up every 3 months for 2 years. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS: Twenty-seven PACG eyes were randomized to receive combined phacoemulsification plus ECP, and 21 PACG eyes underwent phacoemulsification alone. There was no statistically significant difference in mean preoperative IOP between combined phacoemulsification plus ECP and phacoemulsification groups (20.0 mmHg vs. 20.7 mmHg; P = 0.71). Phacoemulsification plus ECP resulted in lower mean postoperative IOP than phacoemulsification alone at all follow-up visits, but the differences only reached statistical significance at 1 month (P = 0.01), 12 months (P = 0.01), and 24 months (P = 0.04) postoperatively. There was no statistically significant difference in mean preoperative number of topical glaucoma drugs between combined phacoemulsification plus ECP and phacoemulsification groups (3.3 vs 3.1, P = 0.71). Combined phacoemulsification plus ECP resulted in lower glaucoma drug requirement than phacoemulsification alone at all follow-up visits, but the differences did not reach statistical significance at any time points postoperatively (P ≥ 0.05). Both groups were comparable in visual improvement, complication rate, need for additional surgical intervention, and visual field changes. CONCLUSIONS: Combined phacoemulsification plus ECP is noninferior to phacoemulsification alone in controlling IOP in PACG eyes with cataract. Combined phacoemulsification plus ECP resulted in lower mean IOP and glaucoma drug requirement than phacoemulsification alone at all follow-up visits in this pilot study, but the differences did not reach statistical significance at the majority of time points. A large-scale randomized controlled trial is in progress to evaluate these differences.

Glaucoma as Neurodegeneration in the Brain.

Glaucoma, a group of diseases characterized by progressive optic nerve degeneration that results in irreversible blindness, can be considered a neurodegenerative disorder of both the eye and the brain. Increasing evidence from human and animal studies have shown that glaucoma shares some common neurodegenerative pathways with Alzheimer's disease (AD) and other tauopathies, such as chronic traumatic encephalopathy (CTE) and frontotemporal dementia. This hypothesis is based on the focal adhesion pathway hypothesis and the spreading hypothesis of tau. Not only has the Apolipoprotein E (APOE) gene been shown to be associated with AD, but also with primary open angle glaucoma (POAG). This review will highlight the relevant literature in the past 20 years from PubMed that show the pathogenic overlap between POAG and AD. Neurodegenerative pathways that contribute to transsynaptic neurodegeneration in AD and other tauopathies might also be similar to those in glaucomatous neurodegeneration.

Comparison of Peripapillary Vessel Density of Acute Nonarteritic Anterior Ischemic Optic Neuropathy and Other Optic Neuropathies With Disc Swelling Using Optical Coherence Tomography Angiography: A Pilot Study.

BACKGROUND: The purpose of this study is to quantitatively compare the peripapillary vessel density (PPVD), measured with optical coherence tomography angiography (OCT-A), between acute nonarteritic anterior ischemic optic neuropathy (NAION) and other causes of disc swelling ("others"). METHODS: In this prospective comparative case series, patients with unilateral disc swelling due to acute NAION (n = 7) and "others" (n = 7) underwent OCT-A scanning of the optic nerve head with a swept-source OCT (Triton DRI-OCT), in addition to functional assessment. OCT-A images were analyzed using an automated customized MATLAB program. Comparison was made between total and 6 sectoral PPVD (radial peripapillary capillary [RPC] and choroid layers) of affected and fellow eyes; and between the 2 groups' affected eyes. Five NAION patients had repeated assessments at 1, 3, and 6 months. RESULTS: Acute NAION eyes had a significantly lower total and superonasal PPVD (both layers) compared to fellow eyes. No such difference was observed in "others" group for the RPC layer. NAION eyes also had significantly lower total RPC PPVD than affected eyes in the "others" group. Over 6 months, NAION eyes had persistently lower RPC PPVD compared to fellow eyes but the reduced choroidal PPVD resolved by 1 month. CONCLUSION: The study demonstrated reduced superonasal and total RPC PPVD in acute NAION, which persisted over 6 months. Because there is currently no single diagnostic test for NAION, use of OCT-A images to analyze RPC PPVD may potentially help distinguish acute NAION from other causes of disc swelling by quantitatively demonstrating capillary dropout in the RPC layer.

Global assessment of arteriolar, venular and capillary changes in normal tension glaucoma.

Microcirculatory insufficiency has been hypothesized in glaucoma pathogenesis. There is a scarcity of data to comprehensively examine the changes in retinal microvasculature and its role in normal tension glaucoma (NTG). We conducted a cross-sectional case-control study and included 168 eyes from 100 NTG patients and 68 healthy subjects. Quantitative retinal arteriolar and venular metrics were measured from retinal photographs using a computer-assisted program. Radial peripapillary capillary network was imaged with OCT-A and quantitative capillary metrics (circumpapillary vessel density (cpVD) and circumpapillary fractal dimension (cpFD)) were measured with a customized MATLAB program. We found that NTG was associated with decreased arteriolar and venular tortuosity, arteriolar branching angle, cpVD and cpFD. Decreased venular caliber, arteriolar and venular branching angles, cpVD and cpFD were associated with thinner average RNFL thickness. Decreased arteriolar and venular branching angles, cpVD and cpFD were also associated with worse standard automated perimetry measurements (mean deviation and visual field index). Compared with retinal arteriolar and venular metrics, regression models based on OCT-A capillary metrics consistently showed stronger associations with NTG and structural and functional measurements in NTG. We concluded that NTG eyes showed generalized microvascular attenuations, in which OCT-A capillary metrics attenuations were more prominent and strongly associated with NTG.

Intraocular pressure control and visual field changes in primary angle closure disease: the CUHK PACG Longitudinal (CUPAL) study.

PURPOSE: To determine the relationship of intraocular pressure (IOP) control with subsequent visual field (VF) deterioration in patients with primary angle closure disease (PACD). METHODS: 419 PACD eyes from 240 Chinese patients were included. Mean IOP and IOP fluctuation were calculated as the average and SD divided by mean IOP, respectively, of all the IOP measured in the initial 18 months for assessment of IOP control. The relationship between IOP control and subsequent VF parameters over time was examined using linear mixed models. VF deterioration was defined as IOP control associated with decreased VF parameters over time with a p value <0.05. We calculated the average of the mean IOPs and IOP fluctuations in the cohort and used these two average values as a cut-off point to define high-threshold (≥average value) or low-threshold (

Atypical presentations of intracranial dysgerminoma mimicking central nervous system inflammatory or demyelinating disease.

OBJECTIVES: The aim of this study is to report a case series of atypical presentations of intracranial dysgerminoma in which the diagnosis was delayed due to clinical and radiographic findings initially suggestive of CNS inflammatory or demyelinating diseases, such as MS. METHODS: This study is a case series detailing the history, clinical presentations, radiographic and laboratory results, and management of three patients with biopsy-proven intracranial dysgerminoma. RESULTS: All three patients demonstrated hyperintense lesions on MRI that were more suggestive of demyelinating or inflammatory diseases, including lesions involving the midbrain and corpus callosum. All three patients were serum positive for oligoclonal bands and negative for both AFP and beta-hCG (these two markers are commonly seen in dysgerminoma cases). One case involved a steroid-responsive tumor whereas the other two cases either did not respond to steroids or steroids were withheld due to uncertainty of etiology. Following biopsy, all three results were consistent with dysgerminoma. CONCLUSION: Clinicians should be aware that dysgerminoma may mimic the clinical and radiographic presentations of demyelinating diseases such as MS. These lesions can cause acute visual loss or diplopia, have MRI and CSF findings that might mimic MS, and have been shown to respond to steroids. Atypical clinical (e.g., headache, dorsal midbrain syndrome, bilateral optic neuropathy) or atypical radiographic features (e.g., mass effect, hydrocephalus) should prompt consideration for repeat imaging and possible biopsy even if serum or CSF tumor markers (beta-hCG and AFP) are negative for dysgerminoma.

Proceedings of the Neuro-Ophthalmology Program of the 33rd Asia-Pacific Academy of Ophthalmology Congress, Hong Kong, 8-11 February 2018.

The 33rd Asia-Pacific Academy of Ophthalmology (APAO) Congress was held on Feb 8-11, 2018 in Hong Kong. This report summarized the highlights of the neuro-ophthalmology program of the Congress, including the scientific symposia (invited and submitted) and the social activities.

The Role of Optical Coherence Tomography in the Acute Management of Neuro-Ophthalmic Diseases.

Optical coherence tomography (OCT) can provide high-speed and high-resolution images of the anatomical structures of the optic nerve head and macula. However, in neuro-ophthalmic conditions that present acutely, structural changes lag functional deficits, and the role of OCT in the acute setting has been challenged. This review aims to summarize the recent literature and evidence supporting the use of OCT in the acute management of some common neuro-ophthalmic scenarios, including the differential diagnosis of optic disc swelling, and in patients with suspected papilledema, optic neuritis, ischemic optic neuropathies, and Leber hereditary optic neuropathy. The limitations of OCT are also discussed.

The use of optical coherence tomography in neuro-ophthalmology.

PURPOSE OF REVIEW: In the last decade, with the advances of optical coherence tomography (OCT) technology, different imaging protocols and analysis algorithms have been introduced to maximize the potential of this diagnostic tool in the evaluation of different eye diseases. This review aims to provide an update on these additional features, with respect to the management of a diverse range of neuro-ophthalmologic conditions. RECENT FINDINGS: Macular ganglion cell complex (mGCC) analysis has been shown to be superior to peripapillary retinal nerve fiber layer (pRNFL) analysis in certain settings, such as differentiating Leber's hereditary optic neuropathy from functional visual loss; monitoring neurodegenerative diseases or multiple sclerosis; and predicting visual loss in nonarteritic ischemic optic neuropathy. mGCC analysis also demonstrates high correlation with perimetry and might serve as an early structural indicator of irreversible neuronal loss. Compared to pRNFL, retinal thickness analysis of the optic nerve head demonstrates better correlation with the severity of papilledema, thus enabling its possible application in detecting raised intracranial pressure, especially in the pediatric group. Upcoming research on emerging OCT technologies including OCT-angiography, enhanced depth imaging, retinal single-layer analysis and portable systems will hopefully further enhance the utility of OCT in the field. SUMMARY: It is crucial for neuro-ophthalmologists to be updated and familiar with these newer OCT imaging protocols and to make appropriate choices for different clinical scenarios, in order to optimize the diagnostic sensitivity and specificity.

Optic Disc and Macular Imaging in Blind Eyes from Non-glaucomatous Optic Neuropathy: A Study with Spectral-domain Optical Coherence Tomography.

The purpose of this study was to determine and compare the optic disc and macular thickness measurements using two spectral-domain optical coherence tomography (SD-OCT) instruments in long-standing blind eyes diagnosed with non-glaucomatous optic neuropathies (NGON). A prospective observational case-series design was used. Twelve eyes from 12 NGON patients with no light perception for at least 6 months underwent optic disc and macular imaging with Cirrus HD-OCT and Spectralis OCT. The correlation between the peripapillary retinal nerve fibre layer (PRNFL) and macular ganglion cell layer and inner plexiform layer (GCL+IPL) thicknesses, and between the duration of no light perception (NLP) and PRNFL/GCL+IPL thicknesses were determined using Spearman's correlation analysis. The mean average PRNFL thickness was 55.9 ± 4.8 µm for Cirrus HD-OCT, which was significantly thicker than that measured by Spectralis OCT (31.9 ± 7.4 µm; p < 0.001). The mean central macular thickness on Cirrus HD-OCT was normal, but there was global thinning at the other macular areas. The mean average GCL+IPL thickness on Cirrus HD-OCT was 51.8 ± 5.8 µm. There was a good correlation between average PRNFL thickness and GCL+IPL thickness (r = 0.830, p = 0.002); however, there was no significant correlation between the duration of NLP to the average PRNFL thickness (on either instruments) or GCL+IPL thickness on Cirrus HD-OCT (p > 0.7). These results show that there was residual PRNFL thickness in NGON eyes with NLP, which varied significantly between SD-OCT instruments. The values of the residual PRNFL and GCL+IPL thicknesses in blind eyes (the "floor" effect) may be useful for prognostic purposes for patients with partial optic atrophy.

Anatomical effects of clear lens extraction by phacoemulsification versus trabeculectomy on anterior chamber drainage angle in primary angle-closure glaucoma (PACG) patients.

PURPOSE: To document the anatomical effects of clear lens extraction by phacoemulsification versus trabeculectomy on anterior chamber angle in patients with primary angle-closure glaucoma (PACG). METHODS: Gonioscopy and ultrasound biomicroscopy (UBM) were performed pre-operatively, and at 1 year after clear lens extraction or trabeculectomy in PACG eyes. RESULTS: Fifty PACG eyes of 50 patients were included. Twenty-six eyes had clear lens extraction by phacoemulsification, while 24 eyes underwent trabeculectomy. The mean extent of synechial angle closure was significantly reduced from 272.3° ± 57.3° to 253.3° ± 70.5° (p = 0.007) by phacoemulsification, but it was only reduced from 285.0° ± 64.6° to 283.1° ± 55.5° (p = 0.32) by trabeculectomy. The mean angle-opening distance at 500 microns from sclera spur (AOD500) measured by UBM was significantly increased from 220.3 ± 93.8 microns to 388.9 ± 134.1 microns (p < 0.001) by clear lens extraction, but decreased from 220.9 ± 79.8 microns to 214.5 ± 70.2 microns (p = 0.11) by trabeculectomy. The mean anterior chamber depth (ACD) measured by UBM was significantly increased from 1,983.8 ± 176.8 microns to 3335.0 ± 174.2 microns (p < 0.001) by clear lens extraction, but decreased from 2,000.2 ± 214.5 microns to 1975.8 ± 218.2 microns (p = 0.001) by trabeculectomy. CONCLUSION: Compared to trabeculectomy, clear lens extraction resulted in a significant reduction in synechial angle closure, and an increase in anterior chamber angle width and anterior chamber depth in PACG eyes without cataract.

The Pathogenesis of Nonarteritic Anterior Ischemic Optic Neuropathy.

Although nonarteritic anterior ischemic optic neuropathy (NAION) is known to occur as a result of ischemic insult to the anterior portion of the optic nerve, its etiology and pathogenesis remain elusive. Because NAION is a nonfatal condition, acute, postmortem histopathologic analysis has never been undertaken. Animal models of NAION have been created with the use of an iodinated derivative of fluorescein, rose bengal. When rose bengal is stimulated with the use of a frequency-doubled neodymium-Yttrium aluminium garnet (YAG) laser diode, vascular endothelial damage may be induced in a precise and focal manner, within the anterior optic nerve. Primate and nonprimate animal models of NAION differ from the human pattern of NAION in the duration of the disease course, as well as the anatomy. The rat lamina cribrosa contains a differing connective tissue structure, which may result in a differing pathogenesis of ischemic insult. Optic disk swelling resolves within 5 days in rats and 14 days in primates; in humans, it is known to persist for up to 6 weeks. Animal models have nonetheless enabled a deeper understanding of the underlying pathologic processes in NAION.

Acute and subacute inflammation of the optic nerve and its sheath: clinical features in Chinese patients.

OBJECTIVE: Inflammation of the optic nerve (optic neuritis) and its sheath (optic perineuritis) can have similar initial clinical presentations. They are less well-defined in the Chinese than in Caucasians, and the aetiology of optic neuritis may also differ depending on ethnicity. The aim of our study was to document the clinical features of acute/subacute optic neuritis/optic perineuritis in Chinese patients. DESIGN: Retrospective case series. SETTING: Hong Kong Eye Hospital, Hospital Authority. PATIENTS: Records of all patients presenting to the Hong Kong Eye Hospital between 2005 and 2008, with their first episode of optic neuritis/optic perineuritis with onset of symptoms within 30 days, were reviewed. MAIN OUTCOME MEASURES: Disease aetiology, clinical features and outcomes. RESULTS: Twenty-nine patients were included (M:F=13:16), with a mean age of 46 years at presentation. Among these, 25 had optic neuritis and four had optic perineuritis; four presented with bilateral optic neuritis. Among the optic neuritis group, 17 (68%) were idiopathic, seven (28%) were related to multiple sclerosis, and one (4%) had neuromyelitis optica. Poor visual outcome in the optic neuritis group was associated with poor visual acuity at presentation and poor visual acuity at the nadir. CONCLUSION: Optic perineuritis and neuromyelitis optica-related optic neuritis were more commonly encountered in our study of Hong Kong Chinese patients than in Caucasian populations. Even in Chinese patients with 'typical' optic neuritis, neuro-imaging and further investigations may be warranted to exclude optic perineuritis/neuromyelitis optica, since Chinese ethnicity is itself an atypical feature. Where neuro-imaging is not readily available, intravenous methylprednisolone may be considered as initial treatment to cover both optic neuritis/optic perineuritis in patients with severe visual loss.

Is four a deadly number for the Chinese?

BACKGROUND: The numbers 4, 14 and 24 are associated with death for Cantonese-speaking Chinese people, as the words for these numbers sound like the words for "death", "must die" and "easy to die", respectively. A previous study in the United States investigating psychological stress engendered by fear of the number 4 found more cardiac deaths in Chinese and Japanese people, compared with white Americans, on the 4th day of the month. OBJECTIVE: To determine whether more cardiac deaths occur in Hong Kong Chinese people on the days of the month with "deathly connotations" (4, 14 and 24). DESIGN: Analysis of mortality data (1995-2000) of the Chinese population of Hong Kong from the Census and Statistics Department of the Hong Kong Government for these three days of the month, compared with the remaining days, according to both the Gregorian and Lunar calendars. RESULTS: There were 17 346 cardiac deaths registered under ICD-9 codes 410-414 in 1995-2000. The mean (+ 1 SD) of the cumulative number of cardiac deaths on each day of the month was 587 (+ 30) for the Gregorian calendar or 573 (+ 24) for the Lunar calendar. The mean number of deaths on the 4th, 14th and 24th day of the month was not significantly different from the mean number of deaths on the remaining days of the month. CONCLUSION: Our study of Hong Kong Chinese people does not support the concept that more cardiac deaths occur in Cantonese people on the 4th, 14th and 24th day of the month.