Outcomes of primary trabeculectomy with mitomycin-C for primary angle closure glaucoma among supervised trainees in a tertiary eye center in Manila.

PURPOSE: To evaluate efficacy and safety of trabeculectomy with mitomycin C (trab-MMC) for primary angle closure glaucoma (PACG) performed by ophthalmology trainees. METHODS: This was a six-year retrospective study of patients with primary trab-MMC with PACG performed by ophthalmology trainees in a tertiary urban eye center. Outcomes included intraocular pressure (IOP), number of medications, and complications. RESULTS: There were 120 PACG eyes that underwent trab-MMC performed by trainees. The mean follow-up duration was 28.6 ± 20.8 months. At 24 months, postoperative IOP decreased from 32.1 ± 12.0 mm Hg to 14.8 ± 6.9 mm Hg (p<0.0001) with decrease in glaucoma medications [0 (0), 0-2; p<0.0001]. Half of surgeries, 64/120 (53.8%) utilized MMC-onlay and the other half, 55/120(46.2%) received MMC sub-tenon injection. Half 60/120 (50.4%) utilized releasable sutures. Majority 55/120 (46.2%) utilized conjunctival closure near the corneal limbus while 34/120 (28.6%) used a conjunctival skirt. Cumulative complete surgical success rates were 63.3%, 55.83%, and 42.5% at 6, 12, and 24 months, respectively. Most complications were minor, including high IOP (25.0%), bleb leaks (13.3%), and cystic blebs (15.0%). Bleb needling was the most common (24.2%) post-op surgical intervention. CONCLUSION: Among supervised ophthalmology trainees in the Philippines, trab-MMC for PACG was effective in lowering IOP long term and decreasing glaucoma medications, and surgical success rates were generally comparable with trainee studies from first world nations. Complications were minor and not sight threatening.

Determinants of pupil diameters and pupil dynamics in an adult Chinese population.

BACKGROUND: To investigate the determinants of pupil diameter (PD), amplitude of pupil diameter change (PD-change) and speed of pupil constriction (SPC) using video anterior segment optical coherence tomography (AS-OCT) in a population-based sample of Chinese adults. METHODS: Chinese adults aged 40 to 80 years who were free from glaucoma were consecutively recruited from the population-based Singapore Chinese Eye Study. The SPC was measured by AS-OCT videography. Univariate and multivariate analyses were performed to examine the effects of demographic and ocular biometric factors (e.g., axial length [AL], anterior chamber depth [ACD], baseline PD, iris thickness at the area of the dilator muscle [ITDMR], iris area [IA], and iris bowing [IB]) on SPC, PD, and PD-change. RESULTS: A total of 266/302 (89.5 %) AS-OCT videos of eligible eyes were available for analysis. Among these subjects, 64.3 % were women, and the mean age (± standard deviation [SD]) was 56 ± 8.3 years. SPC was not associated with sex. In multiple regression analyses, SPC was independently associated with baseline PD (ß = 0.116, p = 0.006). Baseline PD was independently associated with ACD (ß = 0.341, p < 0.001), TISA 500 (ß = -4.513, p < 0.001), IA (ß = -2.796, p < 0.001), and ITDMR (ß = 6.573, p < 0.001). PD-change was independently associated with ACD (ß = 0.256, p < 0.001), IA (ß = -1.507, p < 0.001), IB (ß = 0.630, p = 0.011), and ITDMR (ß = 3.124, p < 0.001). CONCLUSIONS: Among normal eyes in an adult Chinese population, SPC was associated with larger baseline PD. Larger baseline PD and greater PD change form dark to light were associated with greater ACD, with smaller IA and thicker ITDMR.

Retinal vascular caliber between eyes with asymmetric glaucoma.

PURPOSE: To compare differences in retinal arterial and venular caliber (RAC and RVC respectively) between fellow eyes with glaucoma of asymmetric severity. METHODS: We included subjects with bilateral primary glaucoma that had vertical cup-disc ratios (VCDR) >0.2 between both eyes, or visual field (VF) mean deviation (MD) >6.0 decibels (dB) between both eyes. RESULTS: Among 158 subjects, the average RAC in glaucoma eyes was 131.5 ± 17.8 µm vs 141.6 ± 18.8 µm in fellow eyes with mild disease (p < 0.001). RVCs in glaucoma eyes were 201.0 ± 21.4 µm vs 211.7 ± 25.3 µm in fellow eyes with mild disease (p < 0.001). This relationship held in clustered linear regression models adjusted for age, gender, vascular risk factors, visual acuity, axial length, and intraocular pressure, with RVCs narrower in eyes with worse disease vs mild disease. Eyes with worse disease had greater VCDR (0.9 ± 0.1 vs 0.7 ± 0.1, p < 0.001), and worse VF MD (-18.5 ± 8.6 vs -6.6 ± 5.6, p < 0.001). CONCLUSION: In glaucoma with asymmetric severity between fellow eyes, retinal vascular caliber is less in the eye with more severe disease.

Correlation of peripapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer in early to moderate glaucoma using the Cirrus ® widefield analysis (PanoMap ® ).

PURPOSE: To evaluate and correlate the structural changes between peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) + inner plexiform layer (IPL) in different stages of glaucoma using PanoMap ® optical coherence tomography (OCT). DESIGN: Retrospective observational study. METHODS: Glaucoma diagnostic test data were collected from early to moderate open-angle glaucoma patients. The average and minimum GCL + IPL thickness, sectoral GCL + IPL thickness, and the average and sectoral RNFL thickness were correlated with the different glaucoma stages. RESULTS: This study included 157 eyes from 157 glaucoma patients. Patients were grouped into pre-perimetric, early, and moderate glaucoma. The mean average RNFL thickness, RNFL thickness per sector, average GCL + IPL thickness, and minimum GCL + IPL thickness were different between the three groups ( P < 0.001), except for the nasal sector ( P = 0.643). The mean GCL + IPL thickness in all six sectors showed differences between the groups ( P < 0.001), except the superonasal sector ( P < 0.002). The inferior GCL + IPL sector is the thinnest, followed by the inferotemporal sector. There was a strong correlation between the mean average RNFL and the average GCL + IPL thickness in the pre-perimetric group ( r = 0.4963, P < 0.001) and the moderate group ( r = 0.6534, P < 0.001). The early glaucoma group did not show significant correlation ( r = 0.2963, P = 0.0536). CONCLUSION: Peripapillary RNFL and macular GCL + IPL thinning was evident in different stages of glaucoma, with more thinning observed with increasing glaucoma severity. The peripapillary RNFL and macular GCL + IPL average thickness values were highly correlated in the pre-perimetric and moderate stages of glaucoma.

Towards label-free 3D segmentation of optical coherence tomography images of the optic nerve head using deep learning.

Recently proposed deep learning (DL) algorithms for the segmentation of optical coherence tomography (OCT) images to quantify the morphological changes to the optic nerve head (ONH) tissues during glaucoma have limited clinical adoption due to their device specific nature and the difficulty in preparing manual segmentations (training data). We propose a DL-based 3D segmentation framework that is easily translatable across OCT devices in a label-free manner (i.e. without the need to manually re-segment data for each device). Specifically, we developed 2 sets of DL networks: the 'enhancer' (enhance OCT image quality and harmonize image characteristics from 3 devices) and the 'ONH-Net' (3D segmentation of 6 ONH tissues). We found that only when the 'enhancer' was used to preprocess the OCT images, the 'ONH-Net' trained on any of the 3 devices successfully segmented ONH tissues from the other two unseen devices with high performance (Dice coefficients > 0.92). We demonstrate that is possible to automatically segment OCT images from new devices without ever needing manual segmentation data from them.

Investigating the neuroprotective effect of Copolymer-1 in acute primary angle closure - Interim report of a randomized placebo-controlled double-masked clinical trial.

PURPOSE: To investigate the neuroprotective effect of Copolymer-1 (Cop-1) in patients with acute primary angle closure (APAC) in a randomized double-masked controlled trial. METHODS: After initial medical management, APAC patients were randomized to receive either subcutaneous Cop-1 or placebo within 24 hr and at 1 week. After laser peripheral iridotomy (LPI), subjects underwent serial visual field (VF) tests and retinal nerve fibre layer (RNFL) thickness measurements with spectral-domain optical coherence tomography. The primary outcome measure was mean number of progressing points (significant slope of ≥ 1 dB per year sensitivity loss) over 16 weeks based on pointwise linear regression analysis, and the secondary outcome measure was the change in RNFL thickness. RESULTS: Thirty-eight patients (19 in each group) completed the study. Twenty-five (65.8%) were female, the majority being Chinese (86.8%) with mean age 62.5 years (SD 8.1). Patients in the Cop-1 group were found to have mean of 0.32 (SD 0.95) progressing points compared to 2.74 (SD 5.31) in the placebo group (p = 0.09), while 3/19 (15.8%) of Cop-1 treated patients had 1 or more progressing points compared to 7/19 (36.8%) in the placebo group (p = 0.14). There was no difference in change of RNFL thickness between groups (p = 0.57). We found improvement of mean deviation (MD) at week 16 in the Cop-1 group (p = 0.01) compared to worsening of MD in the placebo group (p = 0.04). CONCLUSION: After APAC, there was no difference in VF progression (or RNFL thickness change) between Cop-1 and placebo groups. However, there was improvement of MD in Cop-1 treated patients.

Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR).

PURPOSE: The study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma. METHODS: We studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway-Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions. RESULTS: The mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64. CONCLUSIONS: Smoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR. TRANSLATIONAL RELEVANCE: The application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions.

Selective laser trabeculoplasty.

Selective laser trabeculoplasty (SLT) has been shown to be safe, well tolerated, and effective in intraocular pressure (IOP) reduction as therapy in several forms of open-angle glaucoma. The preservation of trabecular meshwork (TM) architecture and the demonstrated efficacy in lowering IOP make SLT a reasonable and safe alternative to argon laser trabeculoplasty (ALT). SLT may also be effective for cases of failed ALT and is a procedure that may also be repeatable, unlike ALT. SLT is also a simple technique for an ophthalmologist to learn as the large spot size eliminates the need to locate a particular zone of treatment on the TM. SLT has been demonstrated to be effective as primary treatment for open angle glaucoma and can be an effective adjunct in the early treatment of glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or who are noncompliant with their glaucoma medications, without interfering with the success of future surgery.

Glaucoma in retinoblastoma.

The association between retinoblastoma and secondary glaucoma is well known. The most common cause of secondary glaucoma in retinoblastoma is iris neovascularization (NVI) followed by pupillary block and tumor seeding of the anterior chamber. Although glaucoma is a secondary clinical issue in retinoblastoma (RB) management and care, awareness of its presence, revealed by a thorough ocular exam of the anterior segment, can guide the clinician in assessing the overall condition of the affected eye.

Determinants of optical coherence tomography-derived minimum neuroretinal rim width in a normal Chinese population.

PURPOSE: To characterize an optical coherence tomography (OCT)-derived parameter, Bruch's membrane opening-minimum rim width (BMO-MRW), and its association with demographic and clinical parameters in normal Chinese subjects. METHODS: Right eyes of 466 consecutive healthy subjects from a population-based study of Singaporean Chinese underwent Cirrus OCT imaging. The retinal internal limiting membrane (ILM) and BMO were automatically delineated using the built-in Cirrus algorithm. The standard 36 interpolated radial B-scans (72 BMO points, 5° increments) of each optic nerve head were manually extracted from the central circle (3.46-mm diameter). We used Matlab to measure the shortest distance from the BMO points to the ILM. Associations of BMO-MRW with demographic and clinical parameters were evaluated using marginal general estimating equations analysis. RESULTS: There was a slight preponderance of male subjects (50.9%), with a mean age of 54.8 ± 7.63 years. Mean BMO-MRW was 304.67 ± 58.96 µm (range, 173.32-529.23 µm), which was highly associated with OCT-derived disc area (DA) (ß = -91.78, P < 0.001) and rim area (RA) (ß = 194.31, P < 0.001), followed by spherical refractive error (SRE) (ß = -2.23, P = 0.02) and retinal nerve fiber layer (RNFL) thickness (ß = 0.5, P = 0.04), after adjusting for the associated factors such as age, sex, intraocular pressure (IOP), and vertical cup-disc ratio (VCDR). CONCLUSIONS: Disc area and RA had the strongest association with BMO-MRW, followed by SRE and RNFL thickness. The availability of this normative database will facilitate optic nerve head assessment using the BMO-MRW parameter in Chinese subjects.