Scaling the size of perimetric stimuli reduces variability and returns constant thresholds across the visual field.

The conventional stimulus for standard automated perimetry is fixed in size, giving elevated contrast thresholds and reduced test reliability in the periphery. Here, we test the hypothesis that appropriate scaling of the size of perimetric stimuli will return fixed thresholds and reduced variability across the visual field. We derived frequency-of-seeing (FOS) curves in five healthy subjects at central (3 degrees) and peripheral (27 degrees) locations with a method of constant stimuli (MOCS) using a desktop LCD display. FOS curves for a Goldmann III (GIII) stimulus were compared with those for size scaled spots. To consider clinical translation, we tested a further five healthy subjects (22-24 years) with the Melbourne Rapid Fields (MRF) tablet perimeter at several locations spanning 1 degree to 25 degrees from fixation, deriving FOS curves (MOCS) and also conducting repeated adaptive clinical thresholding to assess intra- and interobserver variability. We found that GIII contrast thresholds were significantly elevated in the periphery compared with the parafovea, with concomitant reduction of FOS slope. Using appropriately size scaled spots, threshold and slope differences between these locations were significantly reduced. FOS data collected with the tablet perimeter confirmed that size scaling confers broad equivalence of the shape of the FOS curve across the visual field. Repeated adaptive thresholding with size scaled stimuli gave relatively constant intra-observer variability across the visual field, which compares favorably with published normative data obtained with the GIII stimulus. The reduced variability will improve signal-to-noise ratio for correct classification of normal visual field test results, whereas the lower contrast thresholds yield greater dynamic range, which should improve the ability to reliably monitor moderate defects.

Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity.

IMPORTANCE: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. BACKGROUND: This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. DESIGN: Retrospective chart review at a tertiary institution. SAMPLES: Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. METHODS: Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. MAIN OUTCOME MEASURES: Surgical outcomes as defined in Guidelines from World Glaucoma Association. RESULTS: Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. CONCLUSIONS AND RELEVANCE: Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.

Progressive Macular Vessel Density Loss Observed on Optical Coherence Tomography Angiography in Glaucoma Patients With Single-Hemifield Visual Field Defects.

PRCIS: Faster hemispheric mVD loss was found in the affected hemifield of POAG patients without significant changes in hemispheric thickness. The progression of mVD loss was associated with the severity of VF damage. PURPOSE: To evaluate the changes in macular vessel density (mVD) loss in primary open angle glaucoma (POAG) patients with visual field (VF) defects confined to 1 hemifield. MATERIALS AND METHODS: This longitudinal cohort study used linear mixed models to evaluate the changes in the hemispheric mean total deviation (mTD), mVD, macular ganglion cell complex, macular ganglion cell-inner plexiform layer, and retinal nerve fiber layer between affected hemifields, unaffected hemifields, and healthy controls. RESULTS: Twenty-nine POAG eyes and 25 healthy eyes were followed for an average of 29 months. In POAG eyes, the rates of decline in hemispheric mTD and hemispheric mVD in the affected hemifields were significantly faster than those in the unaffected hemifields (-0.42±1.24 vs. 0.02±0.69 dB/year, P =0.018 and -2.16±1.01 vs. -1.77±0.90% / year, P =0.031, respectively). There were no differences in the rate of hemispheric thickness change between the 2 hemifields. The rate of hemispheric mVD decline in both hemifields of POAG eyes was significantly faster than that of the healthy controls (All P <0.05). An association between the reduced mTD of the VF and the rate of hemispheric mVD loss in the affected hemifield was observed (r=0.484, P =0.008). Faster rates of mVD loss (ß=-1.72±0.80, P =0.050) were significantly related to reduced hemispheric mTD in the multivariate analysis. CONCLUSIONS: Faster hemispheric mVD loss was found in the affected hemifield of POAG patients without significant changes in hemispheric thickness. The progression of mVD loss was associated with the severity of VF damage.

Outcomes of XEN45 gel stent using posterior small incision sub-tenon ab interno insertion (Semi-open) technique.

PURPOSE: To evaluate the 12-month outcomes of a novel posterior small incision sub-tenon ab interno technique of XEN stent insertion ('Semi-open'). METHOD: Consecutive eyes underwent XEN stent insertion with the Semi-open technique by two surgeons between 1st July 2018 and 30th September 2019. All cases received subconjunctival injection of 0.1 mL of mitomycin C 0.2 mg/mL. Eyes with primary open angle glaucoma (OAG), secondary OAG or pseudophakic primary angle closure glaucoma (PACG) were included. Exclusion criteria were phakic PACG, uveitic or neovascular glaucoma and postoperative follow-up <12 months. Primary outcomes were defined by World Glaucoma Association guidelines. Secondary outcomes included change in glaucoma medications, needling rates and complications. RESULTS: We included 37 consecutive eyes of 35 patients with primary OAG (n = 30), secondary OAG (n = 6) and pseudophakic PACG (n = 1). Thirty-one eyes (84%) received a standalone XEN implantation and 6 (16%) underwent XEN implantation combined with phacoemulsification. The IOP reduced from 19.6 ± 6.0 mmHg preoperatively to 11.2 ± 2.6 mmHg at 12 months (P < 0.01). The number of glaucoma agents reduced from 3.49 ± 1.14 preoperatively to 1.57 ± 1.36 at 12 months. At 12 months, qualified success was 97.3% and complete success was 32%, with one case requiring trabeculectomy. Needling was required in 19% of cases over the 12 month follow up. Complications included 19 cases of transient hypotony and 7 cases of transient choroidal effusion. There were no cases of exposure, bleb leak or bleb-related infection. CONCLUSION: Semi-open XEN technique achieves high surgical success rate in the medium-term with relatively low post-operative bleb needling rate.

Decreased macular deep capillary plexus is associated with functional progression of normal tension glaucoma patients with unilateral visual field loss.

PURPOSE: To investigate whether quantitative optical coherence tomography angiography (OCTA) metrics of the superficial/deep macular retina are associated with the development of visual field (VF) loss in the fellow eyes of normal tension glaucoma (NTG) patients with unilateral VF loss. METHODS: A longitudinal study was conducted in which 61 eyes with normal VF (mean VF mean deviation -0.7±1.6 dB) from 61 NTG patients were included. All subjects underwent OCTA imaging, spectral-domain-OCT imaging and VF testing. OCTA metrics of superficial capillary plexus and deep capillary plexus (DCP) in the macular region were measured. Relationships between baseline OCTA metrics, demographics and ocular characteristics and the risk of VF glaucoma progression were analysed with a Cox proportional hazards model. RESULTS: During a mean follow-up of 38 months, 11 fellow eyes (18.0%) with normal VF at baseline were determined to have VF progression, while 21.3% of affected eyes had VF progression. After adjustment for potential confounding factors, decreased baseline DCP in the fellow eyes was significantly associated with future VF progression (HR 1.33, 95% CI 1.03 to 1.73, p=0.031). CONCLUSION: Decreased DCP was associated with a higher risk of developing VF damage in NTG patients with unilateral VF loss. Assessments of DCP may help improve the evaluation of the risk of functional deterioration in fellow eyes with an initially normal VF.

Bilateral consecutive Xen gel stent surgery during pregnancy for uncontrolled early-onset primary open angle glaucoma.

PURPOSE: To report here a case of uncontrolled glaucoma during third-trimester of pregnancy that was treated successfully with bilateral Xen gel stent insertion. OBSERVATIONS: A 35-year-old woman presented during the third trimester of pregnancy with bilateral uncontrolled primary open angle glaucoma. Her disc examination and visual fields were consistent with advanced glaucoma. After failed Selective Laser Trabeculoplasty and maximal medical treatment, including Acetazolamide, she was treated with bilateral consecutive Xen stent surgery with successful control of her intraocular pressure. CONCLUSIONS AND IMPORTANCE: The use of Xen implant may have advantages over traditional trabeculectomy, especially during pregnancy, as the procedure is shorter, with less dependence on on-table antimetabolite and being minimally invasive with sparing of the conjunctiva.

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study.

PURPOSE: To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. METHODS: Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. RESULTS: Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. CONCLUSIONS: Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. TRANSLATIONAL RELEVANCE: The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Six-month Longitudinal Comparison of a Portable Tablet Perimeter With the Humphrey Field Analyzer.

PURPOSE: To establish the medium-term repeatability of the iPad perimetry app Melbourne Rapid Fields (MRF) compared to Humphrey Field Analyzer (HFA) 24-2 SITA-standard and SITA-fast programs. DESIGN: Multicenter longitudinal observational clinical study. METHODS: Sixty patients (stable glaucoma/ocular hypertension/glaucoma suspects) were recruited into a 6-month longitudinal clinical study with visits planned at baseline and at 2, 4, and 6 months. At each visit patients undertook visual field assessment using the MRF perimetry application and either HFA SITA-fast (n = 21) or SITA-standard (n = 39). The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests. Secondary measures were the point-wise threshold and repeatability for each test, as well as test time. RESULTS: MRF was similar to SITA-fast in speed and significantly faster than SITA-standard (MRF 4.6 ± 0.1 minutes vs SITA-fast 4.3 ± 0.2 minutes vs SITA-standard 6.2 ± 0.1 minutes, P < .001). Intraclass correlation coefficients (ICC) between MRF and SITA-fast for MD at the 4 visits ranged from 0.71 to 0.88. ICC values between MRF and SITA-standard for MD ranged from 0.81 to 0.90. Repeatability of MRF MD outcomes was excellent, with ICC for baseline and the 6-month visit being 0.98 (95% confidence interval: 0.96-0.99). In comparison, ICC at 6-month retest for SITA-fast was 0.95 and SITA-standard 0.93. Fewer points changed with the MRF, although for those that did, the MRF gave greater point-wise variability than did the SITA tests. CONCLUSIONS: MRF correlated strongly with HFA across 4 visits over a 6-month period, and has good test-retest reliability. MRF is suitable for monitoring visual fields in settings where conventional perimetry is not readily accessible.

A Comparison of Perimetric Results from a Tablet Perimeter and Humphrey Field Analyzer in Glaucoma Patients.

PURPOSE: To determine the correlation between the perimetric outcomes from perimetry software Melbourne Rapid Fields (MRF) run on an Apple iPad tablet and those from the Humphrey Field Analyzer (HFA). METHODS: The MRF software was designed with features including variable fixation and fast thresholding using Bayes logic. Here, we report a cross-sectional study on 90 eyes from 90 participants: 12 had normal optic nerves and 78 had glaucoma with various degrees of visual field loss (41 mild and 37 moderate-severe). Exclusion criteria were patients with worse than 20/40 vision or recent intraocular surgery. The visual field outcomes of MRF were compared against those returned from the HFA 24-2 SITA standard. Participants were tested twice on the MRF to establish test-retest repeatability. RESULTS: The test durations were shorter on MRF than HFA (5.7 ± 0.1 vs. 6.3 ± 0.1 minutes, P < 0.001). MRF showed a high level of concordance in its outcomes with HFA (intraclass coefficient [ICC] = 0.93 for mean defect [MD] and 0.86 for pattern deviation [PD]) although the MRF tended to give a less negative MD (1.4 dB bias) compared with the HFA. MRF also showed levels of test-retest reliability comparable to HFA (ICC = 0.93 for MD and 0.89 for PD, 95% limits of agreement -4.5 to 4.3 dB). CONCLUSION: The perimetry results from the MRF have a strong correlation to the HFA outcomes. MRF also has test-retest reliability comparable to HFA. TRANSLATIONAL RELEVANCE: Portable tablet perimetry may allow accurate assessment of visual field when standard perimetry machines are unavailable or unsuitable.

Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury.

Advancing age is a major risk factor for many neurodegenerative diseases but the underlying pathophysiology is not clear. We hypothesize that aging impairs the ability of neurons in the central nervous system to recover functionally after injury. To test this in retinal ganglion cells in vivo, we developed an optic nerve "stress test" which monitors the functional capacity of the optic nerve and retina, during and after a subischemic injury induced by intraocular pressure elevation. We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to the potential benefits of therapies that target mitochondria for the protection of the aging retina and optic nerve against injury.

Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts.

PURPOSE: Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. METHODS: Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). RESULTS: POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. CONCLUSIONS: POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Gaze behavior among experts and trainees during optic disc examination: does how we look affect what we see?

PURPOSE: The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination. METHODS: Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction. RESULTS: Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology. CONCLUSIONS: Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.