Policy-Driven, Multimodal Deep Learning for Predicting Visual Fields from the Optic Disc and OCT Imaging.

PURPOSE: To develop and validate a deep learning (DL) system for predicting each point on visual fields (VFs) from disc and OCT imaging and derive a structure-function mapping. DESIGN: Retrospective, cross-sectional database study. PARTICIPANTS: A total of 6437 patients undergoing routine care for glaucoma in 3 clinical sites in the United Kingdom. METHODS: OCT and infrared reflectance (IR) optic disc imaging were paired with the closest VF within 7 days. EfficientNet B2 was used to train 2 single-modality DL models to predict each of the 52 sensitivity points on the 24-2 VF pattern. A policy DL model was designed and trained to fuse the 2 model predictions. MAIN OUTCOME MEASURES: Pointwise mean absolute error (PMAE). RESULTS: A total of 5078 imaging scans to VF pairs were used as a held-out test set to measure the final performance. The improvement in PMAE with the policy model was 0.485 (0.438, 0.533) decibels (dB) compared with the IR image of the disc alone and 0.060 (0.047, 0.073) dB with to the OCT alone. The improvement with the policy fusion model was statistically significant (P < 0.0001). Occlusion masking shows that the DL models learned the correct structure-function mapping in a data-driven, feature agnostic fashion. CONCLUSIONS: The multimodal, policy DL model performed the best; it provided explainable maps of its confidence in fusing data from single modalities and provides a pathway for probing the structure-function relationship in glaucoma.

The heritability and sibling risk of angle closure in Asians.

PURPOSE: To describe the heritability and sibling risk for angle closure. DESIGN: Prospective clinical study. PARTICIPANTS: Probands with primary angle closure (PAC) and primary angle-closure glaucoma (PACG) and their first-degree relatives. METHODS: One hundred probands with PAC and PACG and their first-degree relatives were examined prospectively. All subjects underwent an ophthalmic evaluation that included slit-lamp examination, optic disc evaluation, and gonioscopy. An angle was classified as narrow if the posterior (usually pigmented) trabecular meshwork could be seen for less than 180° of the angle circumference. The heritability of narrow angles was calculated by threshold models. The sibling recurrence and relative risk of having narrow angles compared with the general population was calculated using estimation of sibling genetic risk parameters, corrected for single ascertainment bias. MAIN OUTCOME MEASURES: Heritability and sibling risk for narrow angles. RESULTS: One hundred probands (consisting of 76 subjects with PACG and 24 with PAC) were examined together with 327 first-degree relatives. There were 76 female probands and 24 male probands. Of the first-degree relatives, 146 were male and 181 were female. Of the 327 first-degree relatives, 105 (32.1%) had narrow angles. The heritability of narrow angles was 58.8% overall, with the genetic variance being 2.30 and the phenotypic variance being 3.91. Of the 515 sibling pairs examined, 171 (33.1%) pairs had both siblings unaffected, 113 (21.9%) pairs had both siblings affected, 231 (45.0%) pairs had 1 sibling affected. The sibling recurrence risk for having narrow angles was 49% (95% confidence interval, 41.6%-56.8%), whereas the sibling relative risk for narrow angles was 7.57 (95% confidence interval, 6.41-8.74). CONCLUSIONS: A high heritability of narrow angles of almost 60% was found. Siblings of Chinese patients with PAC or PACG have almost a 50% probability of having narrow angles and are more than 7 times more likely to have narrow angles than the general population.

Lens vault, thickness, and position in Chinese subjects with angle closure.

PURPOSE: To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure. DESIGN: Prospective, comparative study. PARTICIPANTS: One hundred two Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study. METHODS: All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth [ACD] +1/2 LT) and relative LP (RLP; defined as LP/axial length [AL]). MAIN OUTCOME MEASURES: Lens parameters and angle closure. RESULTS: Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 µm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio [OR], 48.1; 95% confidence interval [CI], 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearson's correlation coefficient [PCC], 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2). CONCLUSIONS: Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT.

A multi-centre interventional case series of 259 ab-interno Xen gel implants for glaucoma, with and without combined cataract surgery.

AIMS: To assess the efficacy of Xen in reducing intraocular pressure (IOP) in varying glaucoma subtypes. To assess the effect of combined phacoemulsification. To determine the frequency of complications and explore further bleb management needed. METHODS: Retrospective case note review of all patients undergoing Xen implantation across four centres from August 2015 to May 2017. RESULTS: In total, 259 consecutive surgeries of 226 patients were reviewed. IOP reduced from 19.3 (SD ± 6.0) mmHg preoperatively to 14.2 (SD ± 4.4) at month 12 and 13.5 (SD ± 3.3) at month 18 (p < 0.0001). Medication usage reduced from 2.6 (±1.1) preoperatively to 0.8 (±1.0) at month 12 (p < 0.0001) and 1.1 (±1.3) medications at month 18 (p < 0.0001). Simultaneous phacoemulsification did not alter outcomes as Xen IOP was 14.3 (SD ± 4.7) mmHg and Phaco-Xen was 13.8 (SD ± 2.6) mmHg at month 12 (p = 0.5367). Xen appears to be effective in previous failed filtration surgery. Adverse events included: IOP spikes of ≥30 mmHg in 33 (12.7%) cases, secondary filtration surgery required in 24 (9.3%) cases; implant exposure in 6 (2.3%) cases; persistent hypotonous maculopathy in 5 (1.9%) cases; persistent choroidal effusions in 4 (1.5%) cases; a cyclodialysis cleft secondary to implant insertion in 1 (0.5%) case; and 1 (0.5%) case of endophthalmitis post-implant bleb resuturing. In all, 40.9% of cases required postoperative bleb needling or antimetabolite injection. CONCLUSIONS: Xen reduces IOP and medications at 18 months. Adverse events are uncommon. Careful postoperative surveillance and low threshold for bleb management is needed. Xen is safe and effective in mild to moderate glaucoma.

Kabuki syndrome: new ocular findings but no evidence of 8p22-p23.1 duplications in a clinically defined cohort.

The underlying cause of the multiple congenital anomalies/mental retardation syndrome Kabuki syndrome (KS, OMIM 147920) has not yet been established. We identified seven patients who fulfilled the classical clinical criteria for this syndrome and undertook a detailed clinical, ophthalomological and molecular cytogenetic review. Three of the seven patients had previously undetected ocular anomalies including myopia, ptosis, strabismus and tilted discs. The identification of preventable causes of loss of vision underlines the value of detailed ophthalmologic examination of KS patients. Using BAC fluorescence in situ hybridisation, there was no evidence of the duplication of 8p recently reported by Milunsky and Huang. We conclude that the cause of KS has yet to be established.

High-definition optical coherence tomography imaging of the iridocorneal angle of the eye.

OBJECTIVE: To assess the ability of high-definition optical coherence tomography (HD-OCT) to image the anterior chamber angle. METHODS: Forty-five consecutive subjects with phakic eyes underwent gonioscopy and anterior chamber angle imaging with HD-OCT adapted with a 60-diopter aspheric lens mounted over the imaging aperture. The patients' fixation was directed to the side using an external fixation light, and scans were taken of the temporal and nasal quadrants. The visibility of angle structures was assessed and the diagnosis of angle closure using HD-OCT was compared with that of gonioscopy. RESULTS: The majority of subjects were Chinese (91.1%) and female (62.2%). Cross-sectional HD-OCT allowed in vivo visualization of the scleral spur in 71 of 90 quadrants (78.9%) and the termination of the Descemet membrane (Schwalbe line) in 84 of 90 quadrants (93.3%). It was possible to image the trabecular meshwork in 56 quadrants (62.2%). Angle closure was observed in 17 eyes with gonioscopy and 12 eyes with HD-OCT (P = .12, McNemar test). The 2 modalities showed good agreement for angle closure diagnosis by quadrant (kappa = 0.65). CONCLUSION: The adapted HD-OCT provided magnified views of the anterior chamber angle and allowed visualization of the Schwalbe line and trabecular meshwork in most eyes.

Variation of angle parameters in asians: an anterior segment optical coherence tomography study in a population of singapore malays.

PURPOSE: To assess variations in angle parameters using anterior segment optical coherence tomography (AS-OCT) and to investigate demographic, ocular and systemic associations of angle width. METHODS: This was a substudy of a population based, cross-sectional survey of 3280 (78.7% response rate) Malay people aged 40 to 80 years in Singapore. All participants underwent a standardized interview and ocular and systemic examination. AS-OCT was performed on 291 consecutive patients in standardized dark conditions. Angle opening distance (AOD-500) and trabecular-iris space area (TISA-500) 500 microm from the scleral spur were determined for the nasal and temporal angles. Anterior chamber depth (ACD) was also measured. RESULTS: AS-OCT measurements were analyzed in 239 (82.1%) right eyes. Mean AOD 500 was smaller in women than in men, both nasally (0.255 vs. 0.293 mm, P = 0.026) and temporally (0.245 vs. 0.286 mm, P = 0.023). Mean TISA-500 was smaller in women in the nasal quadrant only (0.104 vs. 0.117 mm, P = 0.035). Mean ACD was smaller in women than in men (2.71 vs. 2.87 mm, P = 0.001). Multiple linear regression showed that axial length and ACD were significantly associated with AOD-500 and TISA-500 both nasally (adjusted R(2) = 0.34 for AOD-500 and 0.20 for TISA-500) and temporally (adjusted R(2) = 0.35 for AOD-500 and 0.24 for TISA-500). Body mass index, HbA(1c), systolic blood pressure, intraocular pressure, cup-to-disc ratio, and central corneal thickness were not significantly associated with AOD-500, TISA-500, or ACD. CONCLUSIONS: In this Malay population, angle width measured by AS-OCT was smaller in women than in men, and in eyes with shorter axial length and shallower ACD.

Angle-closure: risk factors, diagnosis and treatment.

INTRODUCTION: Primary angle-closure glaucoma (PACG) is the leading cause of blindness in East Asia. The disease can be classified into primary angle-closure suspect, primary angle closure (PAC), and PACG. Pupil-block, anterior nonpupil-block (plateau iris and peripheral iris crowding), lens related and retrolenticular mechanisms have been suggested as the four main mechanisms of angle closure. RISK FACTORS: The risk factors for PAC are female gender, increasing age, Inuit or East Asian ethnicity, shallow anterior chamber, shorter axial length, and genetic factors. DIAGNOSIS: The diagnosis of acute PAC is mainly clinical. Diagnosis can be made with careful slit lamp examination, including intraocular pressure (IOP) measurement and gonioscopy. The diagnosis of chronic PAC and chronic PACG also require a careful history to assess risk factors, slit lamp examination including IOP and gonioscopy. Further investigations may also be required including visual fields, ultrasound biomicroscopy, and other imaging methods. MANAGEMENT: In acute PAC, rapid control of the IOP needs to be achieved to limit optic-nerve damage. This can be carried out medically, and/or by laser iridoplasty. Both the affected and fellow eye should undergo laser peripheral iridotomy (PI). The aim of treating chronic PAC is to eliminate the underlying pathophysiological mechanism and to reduce IOP. This can be done by carrying out laser PI, iridoplasty, medical therapy, or surgery (trabeculectomy, lens extraction, combined lens extraction with trabeculectomy and goniosynechialysis). CONCLUSION: Angle-closure glaucoma is usually an aggressive, visually destructive disease. By assessing the risk factors and diagnosing the mechanism involved in a patient's condition, the management of that patient can be tailored appropriately.

Evidence of retinal vascular narrowing in glaucomatous eyes in an Asian population.

PURPOSE: To examine the relationship between retinal vascular caliber and glaucoma in an Asian population. METHODS: A population-based, cross-sectional study of 3019 persons of Asian Malay ethnicity aged 40 to 80 years residing in Singapore. All participants had dilated digital retinal photographs taken of both eyes. From these, retinal vascular caliber was measured with a computer-based technique according to a standardized protocol. Glaucoma was diagnosed based on the International Society of Geographic and Epidemiologic Ophthalmology classification and included people with glaucomatous optic neuropathy and compatible visual field loss. RESULTS: There were 127 (4.2%) participants with glaucoma. Mean retinal arteriolar and venular calibers were significantly narrower in persons with than in those without glaucoma (136.4 microm vs. 139.7 microm, P = 0.02 and 209.2 microm vs. 219.7 microm, P < 0.001, respectively). After adjusting for age, sex, smoking, IOP, and other vascular risk factors, persons with narrower retinal arteriolar and venular caliber were more likely to have glaucoma (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.07-1.56 and OR, 1.49; 95% CI, 1.24-1.79, for each SD reduction in arteriolar and venular caliber, respectively) and a vertical cup-to-disc ratio >or= 0.7 (OR, 1.35; 95% CI, 1.12-1.63 and OR, 1.65; 95% CI, 1.38-1.98, respectively). Retinal vascular caliber was not associated with intraocular pressure. CONCLUSIONS: These findings support an association of narrower retinal arteriolar and venular caliber changes with glaucomatous optic neuropathy, independent of intraocular pressure.

Determinants of the optic cup to disc ratio in an Asian population: the Singapore Malay Eye Study (SiMES).

OBJECTIVE: To describe the distribution and determinants of the optic cup to disc ratio (CDR) in Malay adults in Singapore. METHODS: This population-based, age-stratified study examined 3280 Malay people aged 40 to 80 years in Singapore. Participants underwent a standardized interview and an ocular examination. A slitlamp examination measured the vertical dimensions of the disc and cup, excluding areas of peripapillary atrophy and the Elschnig scleral ring. RESULTS: Vertical CDR was recorded for 3228 right eyes and 3237 left eyes. The mean (SD) CDR was 0.40 (0.15) in both eyes. The CDR in the right eye increased with age (P < .001) and was greater in men vs women (age-adjusted CDR, 0.42 vs 0.39; P < .001). In multiple linear regression, significant determinants of greater CDR were increasing age, male sex, higher intraocular pressure (IOP), lower diastolic blood pressure, lower body mass index, and previous cataract surgery. Of these, higher IOP was the most important determinant of the CDR. After excluding 149 persons with glaucoma, male sex, higher IOP, lower diastolic blood pressure, lower body mass index, and diabetes mellitus were significant predictors of greater CDR. CONCLUSION: Greater vertical CDR was related to male sex, higher IOP, lower diastolic blood pressure, and lower body mass index.