Impact of a short online course on the accuracy of non-ophthalmic diabetic retinopathy graders in recognising glaucomatous optic nerves in Vietnam.

PURPOSE: To test an online training course for non-ophthalmic diabetic retinopathy (DR) graders for recognition of glaucomatous optic nerves in Vietnam. METHODS: This was an uncontrolled, experimental, before-and-after study in which 43 non-ophthalmic DR graders underwent baseline testing on a standard image set, completed a self-paced, online training course and were retested using the same photographs presented randomly. Twenty-nine local ophthalmologists completed the same test without the training course. DR graders then underwent additional one-to-one training by a glaucoma specialist and were retested. Test performance (% correct, compared with consensus grades from four fellowship-trained glaucoma experts), sensitivity, specificity, positive and negative predictive value, and area under the receiver operating (AUC) curve, were computed. RESULTS: Mean age of DR graders (32.6±5.5 years) did not differ from ophthalmologists (32.3±7.3 years, p=0.13). Online training required a mean of 297.9 (SD 144.6) minutes. Graders' mean baseline score (33.3%±14.3%) improved significantly after training (55.8%±12.6%, p<0.001), and post-training score did not differ from ophthalmologists (58.7±15.4%, p=0.384). Although grader sensitivity reduced before [85.5% (95% CI 83.5% to 87.3%)] versus after [80.4% (78.3% to 82.4%)] training, specificity improved significantly [47.8 (44.9 to 50.7) vs 79.8 (77.3 to 82.0), p<0.001]. Grader AUC also improved after training [66.6 (64.9 to 68.3)] to [80.1 (78.5 to 81.6), p<0.001]. Additional one-to-one grader training by a glaucoma specialist did not further improve grader scores. CONCLUSION: Non-ophthalmic DR graders can be trained to recognise glaucoma using a short online course in this setting, with no additional benefit from more expensive one-to-one training. After 5-hour online training in recognising glaucomatous optic nerve head, scores of non-ophthalmic DR graders doubled, and did not differ from local ophthalmologists. Intensive one-to-one training did not further improve performance.

Deep Learning for Localized Detection of Optic Disc Hemorrhages.

PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n = 1340), validation (n = 167), and test (n = 165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95% CI = 0.857-0.964) across all held-out images (n = 165 photographs), which was significantly superior to the image classification model (AUC = 0.845, 95% CI = 0.740-0.912; P = .006). At an operating point selected for high specificity, the model achieved a specificity of 94.3% and a sensitivity of 70.0%, which was statistically indistinguishable from an expert clinician (P = .7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7% and a specificity of 73.3%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.

Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

PURPOSE: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care. DESIGN: Observational study. PARTICIPANTS: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years. METHODS: This study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye. MAIN OUTCOME MEASURES: Prevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes). RESULTS: Based on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively. CONCLUSIONS: This study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Short-Term Changes in the Photopic Negative Response Following Intraocular Pressure Lowering in Glaucoma.

Purpose: To evaluate the short-term changes in inner retinal function using the photopic negative response (PhNR) after intraocular pressure (IOP) reduction in glaucoma. Methods: Forty-seven participants with glaucoma who were commencing a new or additional IOP-lowering therapy (treatment group) and 39 participants with stable glaucoma (control group) were recruited. IOP, visual field, retinal nerve fiber layer thickness, and electroretinograms (ERGs) were recorded at baseline and at a follow-up visit (3 ± 2 months). An optimized protocol developed for a portable ERG device was used to record the PhNR. The PhNR saturated amplitude (Vmax), Vmax ratio, semi-saturation constant (K), and slope of the Naka-Rushton function were analyzed. Results: A significant percentage reduction in IOP was observed in the treatment group (28 ± 3%) compared to the control group (2 ± 3%; P < 0.0001). For PhNR Vmax, there was no significant interaction (F1,83 = 2.099, P = 0.15), but there was a significant difference between the two time points (F1,83 = 5.689, P = 0.019). Post hoc analysis showed a significant difference between baseline and 3 months in the treatment group (mean difference, 1.23 µV; 95% confidence interval [CI], 0.24-2.22) but not in the control group (0.30 µV; 95% CI, 0.78-1.38). K and slope were not significantly different in either group. Improvement beyond test-retest variability was seen in 17% of participants in the treatment group compared to 3% in the control group (P = 0.007, χ2 test). Conclusions: The optimized protocol for measuring the PhNR detected short-term improvements in a proportion of participants following IOP reduction, although the majority showed no change.

Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.

IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS: Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.

Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1).

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-µg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations. DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study. PARTICIPANTS: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout. METHODS: Study eyes received bimatoprost implant 10 µg (n = 198) or 15 µg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit. MAIN OUTCOME MEASURES: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). RESULTS: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-µg implant, 15-µg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-µg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-µg implant) and 21.8% (15-µg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit. CONCLUSIONS: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-µg implant over the 15-µg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.

The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort.

Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF, TMEM98, MFRP, and PRSS56. Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.

Effectiveness of an innovative and comprehensive eye care model for individuals in residential care facilities: results of the residential ocular care (ROC) multicentred randomised controlled trial.

BACKGROUND: To assess the clinical and patient-centred effectiveness of a novel residential ocular care (ROC) model in Australian individuals residing in residential care. METHODS: In this prospective, multicentred, randomised controlled trial conducted in 38 Australian aged-care facilities (2015-2017), 178 visually impaired individuals living in residential care facilities (mean age ±SD: 83.9±8.6 years; 65.7% women) were cluster randomised to ROC (n=95) or usual care (n=83) pathways. The ROC arm comprised a tailored and comprehensive within-site eye examination and care rehabilitation pathway, while usual care participants were given a referral to an external eyecare provider. Outcomes included presenting distance and near visual acuity (PNVA); Rasch-transformed Reading, Emotional and Mobility scores from the Impact of Vision Impairment questionnaire; quality of vision (QoV comprising Rasch-transformed Frequency, Severity and Bother domains) scores; Euroqol-5-Dimensions (raw scores); Cornell Scale for Depression (raw scores) and 6-month falls frequency, assessed at baseline and 6 months post intervention. Within-group and between-group comparisons were conducted using linear mixed models, adjusted for baseline differences in characteristics between the two arms. RESULTS: At 6 months, intention-to-treat analyses showed significant between-group improvements in ROC residents compared with usual care for PNVA, Emotional and QoV scores (all p<0.05) These significant findings were retained in per-protocol analyses. No other between-group changes were observed. CONCLUSION: Our ROC model was effective in improving near vision, emotional well-being and perceived burden of vision-related symptoms in residential care dwellers in Australia with vision impairment. Future studies to evaluate the cost effectiveness and implementation of ROC in Australia are warranted.

Calcification of hydrophilic acrylic intraocular lenses following secondary surgical procedures in the anterior and posterior segments.

AIMS: To report 15 cases of intraocular lens (IOL) calcification following intraocular surgery and to identify common risk factors. METHODS: A retrospective case review of patients with IOL calcification reported from the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and six surgeons in private practice in the Australian states of Victoria, New South Wales and Queensland. RESULTS: 15 cases of IOL calcification were identified. Eight cases were in hydrophilic acrylic IOLs and seven in hydrophilic acrylic IOLs with hydrophobic surface properties. Five cases occurred following intraocular injection of gas during endothelial keratoplasties. Two cases occurred following pars plana vitrectomy where gas was used. The remaining eight cases did not involve the injection of any intraocular gas; six cases were following trabeculectomy surgery, and two cases were after insertion of a 'piggyback' sulcus IOL. In each case, the calcification had a characteristic pattern, being centrally placed in the pupillary zone, mainly affecting the anterior lens surface. CONCLUSION: The aetiology of IOL calcification is not fully understood, although there are known risk factors such as using hydrophilic acrylic materials and the use of intraocular gas. Surgical consideration of a patient's ocular comorbidities before IOL implantation is an important tool to mitigate some of this risk.

Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues.

PURPOSE: To explore the ocular distribution of bimatoprost after intracameral administration of a biodegradable sustained-release bimatoprost implant (Bimatoprost SR) versus repeated topical administration of bimatoprost 0.03% ophthalmic solution in dogs. Bimatoprost SR and topical bimatoprost 0.03% previously were shown to have similar intraocular pressure-lowering effects in humans in a phase 1/2 clinical trial. METHODS: Twenty-four beagle dogs received either once-daily topical bimatoprost 0.03% for 7 days or a bilateral intracameral administration of Bimatoprost SR (15 µg). At predetermined time points, ocular tissues were collected and concentrations of bimatoprost and bimatoprost acid were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Bimatoprost SR administration enhanced delivery of study drug to a site of action [iris-ciliary body (ICB)] compared with topical bimatoprost (Cmax [bimatoprost+bimatoprost acid] = 18,200 and 4.13 ng/g, respectively). However, distribution of drug to tissues associated with prostaglandin analog (PGA)-related side effects (i.e., bulbar conjunctiva, eyelid margins, and periorbital fat) was limited following Bimatoprost SR administration (Cmax [bimatoprost+bimatoprost acid] = BLQ [beneath the limit of quantitation] to 0.354 ng/g) compared with topical dosing (Cmax [bimatoprost+bimatoprost acid] = 36.6-2,110 ng/g). CONCLUSIONS: Bimatoprost SR administration in dogs selectively delivered drug to the ICB with low or undetectable drug levels in ocular surface and extraocular tissues. Use of Bimatoprost SR for glaucoma treatment may reduce the incidence of adverse events typically associated with topical PGAs by targeting bimatoprost delivery to the key site of action of the PGA class and reducing exposure to off-target tissues.

Improving eye care in residential aged care facilities using the Residential Ocular Care (ROC) model: study protocol for a multicentered, prospective, customized, and cluster randomized controlled trial in Australia.

BACKGROUND: Older adults in residential aged care facilities have unnecessarily high levels of vision impairment (VI) which are largely treatable or correctable. However, no current comprehensive eye health service model exists in this setting in Australia. We aimed to determine the clinical, person-centered, and economic effectiveness of a novel eye care model, the Residential Ocular Care (ROC). METHODS/DESIGN: This protocol describes a multicentered, prospective, randomized controlled trial. A total of 395 participants with distance vision < 6/12 (0.30 LogMAR) and/or near vision N8 (1.00 M) or worse will be recruited from 38 urban and rural aged care facilities across Victoria, Australia. Aged care facilities will be randomized (1:1) to one of two parallel groups. Participants in the ROC group will receive a comprehensive and tailored eye care pathway that includes, as necessary, refraction and spectacle provision, cataract surgery, low vision rehabilitation, and/or a referral to an ophthalmologist for funded treatment. Usual care participants will be referred for an evaluation to the eye care service associated with the facility or an eye care provider of their choice. The primary outcome will be presenting near and distance vision assessed at the two- and six-month follow-up visits, post baseline. Secondary outcomes will include vision-specific quality of life, mobility, falls, depression, and eye care utilization at two and six months. An incremental cost-effectiveness analysis will also be undertaken. DISCUSSION: The ROC study is the first multicentered, prospective, customized, and cluster randomized controlled trial in Australia to determine the effectiveness of a comprehensive and tailored eye care model for people residing in aged care facilities. Results from this trial will assist health and social care planners in implementing similar innovative models of care for this growing segment of the population in Australia and elsewhere. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12615000587505 . Registered on 4 June 2015 - retrospectively registered.

Baseline Detrending for the Photopic Negative Response.

PURPOSE: The photopic negative response (PhNR) of the light-adapted electroretinogram (ERG) holds promise as an objective marker of retinal ganglion cell function. We compared baseline detrending methods to improve PhNR repeatability without compromising its diagnostic ability in glaucoma. METHODS: Photopic ERGs were recorded in 20 glaucoma and 18 age-matched control participants. A total of 50 brief, red-flashes (1.6 cd.s/m2) on a blue background (10 photopic cd/m2) were delivered using the RETeval device. Detrending methods compared were: (1) increasing the high-pass filter from 1 to 10 Hz and (2) estimating and removing the trend with an increasing polynomial (order from 1-10) applied to the prestimulus interval, prestimulus and postsignal interval, or the whole ERG signal. Coefficient of repeatability (COR%), unpaired Student's t-test, and area under the receiver operating characteristic curve (AUC) were used to compare the detrending methods. RESULTS: Most detrending methods improved PhNR test-retest repeatability compared to the International Society for Clinical Electrophysiology of Vision (ISCEV) recommended 0.3 to 300 Hz band-pass filter (COR% ± 200%). In particular, detrending with a polynomial (order 3) applied to the whole signal performed the best (COR% ± 44%) while achieving similar diagnostic ability as ISCEV band-pass (AUC 0.74 vs. 0.75, respectively). However, over-correcting with higher orders of processing can cause waveform distortion and reduce diagnostic ability. CONCLUSIONS: Baseline detrending can improve the PhNR repeatability without compromising its clinical use in glaucoma. Further studies exploring more complex processing methods are encouraged. TRANSLATIONAL RELEVANCE: Baseline detrending can significantly improve the quality of the PhNR.

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma.

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

Optimizing a Portable ERG Device for Glaucoma Clinic: The Effect of Interstimulus Frequency on the Photopic Negative Response.

PURPOSE: The purpose of this study was to investigate the effect of interstimulus frequency on the photopic negative response (PhNR) in the clinical electroretinogram (ERG) in glaucoma and healthy eyes. METHODS: Participants with open angle glaucoma (n = 15) and age-matched controls (n = 20) were recruited. Photopic ERGs were recorded in one eye using five frequencies (1-5 Hz) delivered in random order. ERGs were analyzed for changes to amplitude and timing between groups and interstimulus frequency. Coefficient of variation (CoV) was used to examine variability within recordings for each frequency. RESULTS: While the a-wave and b-wave showed minimal alteration, the PhNR was highly sensitive to changes in interstimulus frequency. The PhNR signal was largest at 1 Hz and steadily diminished with higher frequencies in both control and glaucoma groups. Significant differences in PhNR amplitude were found between controls and glaucoma groups at 2 and 3 Hz. While 1 Hz delivered the largest PhNR, it also showed a significantly greater CoV compared to other frequencies. CONCLUSIONS: An interstimulus frequency of 2 Hz was optimal for recording the PhNR, creating a good balance between testing time and signal quality. A higher frequency could be used to further shorten clinical testing times; however, this may compromise its clinical utility by dampening the PhNR. TRANSLATIONAL RELEVANCE: Here we show the importance of considering flash interstimulus frequency when designing ERG protocols for recording the PhNR as while higher frequencies can shorten test times, they also have considerable effects on the PhNR.

A Comparison of the RETeval Sensor Strip and DTL Electrode for Recording the Photopic Negative Response.

PURPOSE: To compare the RETeval sensor strip and Dawson-Trick-Litzkow (DTL) electrodes for recording the photopic negative response (PhNR) using a portable electroretinogram (ERG) device in eyes with and without glaucoma. METHODS: Twenty-six control and 31 glaucoma or glaucoma-suspect participants were recruited. Photopic ERGs were recorded with sensor strip and DTL electrodes in random order using the LKC RETeval device. Stimuli consisted of brief, red flashes (1.7 cd.s/m2) on a blue background (photopic 10 cd/m2). The PhNR amplitude was measured from baseline to trough and also expressed as a ratio over the b-wave amplitude. RESULTS: The sensor strip-recorded PhNR amplitude was significantly attenuated (mean ± standard deviation [SD], 4.8 ± 2.1 vs. 12.7 ± 4.8 µV, P < 0.0001), with lower signal-to-noise ratio (SNR; 5.5 ± 2.1 vs. 8.1 ± 3.9, P < 0.0001), and a trend toward a larger PhNR/b-wave ratio compared with DTL electrodes. The PhNR amplitude, implicit time and PhNR/b-wave ratio correlated with visual field mean light sensitivity, although this fell short of significance for the sensor strip recorded PhNR amplitude. The electrodes demonstrated similar intersession repeatability with a coefficient of repeatability of ±27% and ±28% for the DTL and sensor strip, respectively. CONCLUSIONS: Sensor strip electrodes are a viable alternative for recording reproducible PhNRs, especially when values are normalized to the b-wave. However, DTL electrodes should be considered in cases of attenuated PhNR, or in elevated noise levels, due to its better signal-to-noise quality. TRANSLATIONAL RELEVANCE: Sensor strip electrodes can simplify PhNR recordings in the clinic, potentially eliminating the need for an experienced operator.

Blebs, Barriers, and Bagpipes: Why is It so Hard?

Doug Johnson was a clinician-scientist who made great contributions to the understanding of outflow from the eye. This lecture is in honour of Doug and explores the author's understanding of outflow in the surgical context. HOW TO CITE THIS ARTICLE: Coote M. Blebs, Barriers, and Bagpipes: Why is It so Hard? J Curr Glaucoma Pract 2016; 10(3):79-84.

Porosity of Bleb Capsule declines rapidly with Fluid Challenge.

INTRODUCTION: The porosity of the fibrous capsule around a glaucoma drainage device (GDD) may be the most important functional attribute. The factors that determine capsular porosity are not well understood. Failed GDD surgeries are usually associated with thick impervious capsules and components of aqueous have been implicated in this process. PURPOSE: In this study, we interrogated the effect of passage of nonaqueous fluid on capsular porosity in mature (but aqueous naïve) blebs in a previously reported GDD model (the "Center for Eye Research Australia Implant"). MATERIALS AND METHODS: The study was performed at two centers using 17 New Zealand White (NZW) rabbits. An experimental GDD was implanted into the subconjunctival space but without connection to the anterior chamber. After 28 days, balanced salt solution (BSS) was passed through the implant for 30 to 40 minutes at 12 mm Hg. Capsular porosity was measured as flow (µL/min) at a constant pressure. Porosity of the capsule was retested at 3 and 6 days. RESULTS: There was a marked reduction in capsular porosity within 3 days of exposure to BSS (fluid challenge). Even though the baseline porosity was significantly different in the two groups (3.00 ± 0.5 µL/min and 29.67 ± 12.12 µL/min, p < 0.001), the effect of passage of BSS was similar. Capsular porosity fell by approximately 80% in both groups from baseline after single BSS challenge. Capsular thickness was significantly less in Advanced Eye Center (AEC) rabbits at baseline. There was no change in the capsular thickness before and after single fluid challenge. CONCLUSION: Passage of BSS at physiological pressures for under 40 minutes caused marked reduction in the porosity of the fibrous capsule within 3 days. This was not associated with any significant thickening of the fibrous capsule within this time frame. HOW TO CITE THIS ARTICLE: Pandav SS, Ross CM, Thattaruthody F, Nada R, Singh N, Gautam N, Beirne S, Wallace GG, Sherwood MB, Crowston JG, Coote M. Porosity of Bleb Capsule declines rapidly with Fluid Challenge. J Curr Glaucoma Pract 2016;10(3):91-96.

A Novel Method of Quantitative Anterior Chamber Depth Estimation Using Temporal Perpendicular Digital Photography.

PURPOSE: We hypothesize that: (1) Anterior chamber depth (ACD) is correlated with the relative anteroposterior position of the pupillary image, as viewed from the temporal side. (2) Such a correlation may be used as a simple quantitative tool for estimation of ACD. METHODS: Two hundred sixty-six phakic eyes had lateral digital photographs taken from the temporal side, perpendicular to the visual axis, and underwent optical biometry (Nidek AL scanner). The relative anteroposterior position of the pupillary image was expressed using the ratio between: (1) lateral photographic temporal limbus to pupil distance ("E") and (2) lateral photographic temporal limbus to cornea distance ("Z"). In the first chronological half of patients (Correlation Series), E:Z ratio (EZR) was correlated with optical biometric ACD. The correlation equation was then used to predict ACD in the second half of patients (Prediction Series) and compared to their biometric ACD for agreement analysis. RESULTS: A strong linear correlation was found between EZR and ACD, R = -0.91, R2 = 0.81. Bland-Altman analysis showed good agreement between predicted ACD using this method and the optical biometric ACD. The mean error was -0.013 mm (range -0.377 to 0.336 mm), standard deviation 0.166 mm. The 95% limits of agreement were ±0.33 mm. CONCLUSIONS: Lateral digital photography and EZR calculation is a novel method to quantitatively estimate ACD, requiring minimal equipment and training. TRANSLATIONAL RELEVANCE: EZ ratio may be employed in screening for angle closure glaucoma. It may also be helpful in outpatient medical clinic settings, where doctors need to judge the safety of topical or systemic pupil-dilating medications versus their risk of triggering acute angle closure glaucoma. Similarly, non ophthalmologists may use it to estimate the likelihood of acute angle closure glaucoma in emergency presentations.

Postoperative cystoid macular oedema in a patient on fingolimod.

We describe the first case of fingolimod-associated bilateral cystoid macular oedema (CMO) following uncomplicated cataract surgery. A 57-year-old woman has been on fingolimod for the past 2 years for the treatment of relapsing-remitting multiple sclerosis. She underwent uneventful consecutive cataract surgery 2 weeks apart. Three weeks following the second cataract operation, she reported gradual-onset blurred vision bilaterally. Examination revealed mildly reduced visual acuity and bilateral CMO. Treatment with topical corticosteroids and non-steroidal anti-inflammatory eye drops, as well as cessation of fingolimod in collaboration with the neurologist, resulted in complete resolution of the CMO. Patients on fingolimod are likely to be at increased risk of developing postoperative CMO.