Development and evaluation of Order of Magnitude (OM): a virtual reality-based visual field analyzer for glaucoma detection.

PURPOSE: This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. METHODS: The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. RESULTS: We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. CONCLUSION: These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.

Bilateral Optic Neuropathy Associated with Acute Inhaled Marijuana Use: Case Report and Review of the Literature.

Marijuana is the most commonly used federally illegal drug in the United States. Acute marijuana use is associated with several cardiovascular and neuropsychological adverse effects. Ocular complications of marijuana abuse are very rare. Herein, we present the first report of bilateral optic neuropathy following smoking marijuana. A 28-year-old man presented to the emergency room with sudden onset of bilateral blurring of the inferior visual field 8 h after smoking marijuana. His best-corrected visual acuity was 20/30 in the right eye and 20/20 in the left eye. Fundus examination revealed blurring of the optic disc margins in both eyes and a splinter haemorrhage in the right eye. Bilateral inferior visual field defects were detected with greater severity on the right side. Optical coherence tomography confirmed the diagnosis of bilateral optic neuropathy. A urine drug screen test was positive for tetrahydrocannabinol, which is the primary active ingredient in cannabinoids. The rest of the neurological examination and imaging were normal. The patient was treated with intravenous corticosteroids and an anti-platelet drug. His vision recovered to 20/20 in both eyes, with complete resolution of the field defect over a follow-up of 6 months. Optic neuropathy following marijuana abuse is unusual. The results of our report emphasise the need for awareness of marijuana-associated optic neuropathy as part of ocular adverse effects of marijuana intoxication.

Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset.

PURPOSE: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). DESIGN: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial. PARTICIPANTS: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included. METHODS: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 µl) or to sham injection. The left eye received the treatment not allocated to the right eye. MAIN OUTCOME MEASURES: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96. RESULTS: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively. CONCLUSIONS: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes.

Consistency between optical coherence tomography and humphrey visual field for evaluating glaucomatous defects in high myopic eyes.

BACKGROUND: The study is to investigate the influence of high myopia on the consistency between optical coherence tomography (OCT) and visual field in primary open-angle glaucoma (POAG). METHODS: We enrolled 37 patients with POAG with high myopia (POAG-HM group), 27 patients with POAG without high myopia (POAG group), and 29 controls with high myopia (HM group). All subjects underwent Humphrey perimetry (30-2 and 10-2 algorithms). The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured using Cirrus HD-OCT. Spearman's rank correlation analysis was used to determine correlations between OCT and perimetric parameters. Agreement was analyzed by cross-classification and weighted κ statistics. RESULTS: In POAG group, the cross-classification analysis showed strong agreement between the inferior temporal GCIPL thickness and the mean sensitivity (MS) of 10-2 algorithms (κ = 0.5447, P = 0.0048), and good agreement between the superior and inferior RNFL thicknesses and 30-2 MS (κ = 0.4407 and 0.4815; P < 0.05). In the POAG-HM group, only the inferior temporal GCIPL thickness showed good agreement with 10-2 MS (κ = 0.3155, P = 0.0289) and none of the RNFL sectors were in good agreement with the corresponding MS. CONCLUSIONS: In POAG patients with high myopia, changes in macular measurements were in accordance with visual field defects, and RNFL thickness did not consistently decline with visual field defects due to the effects of high myopia. This study suggests that during diagnosis and follow-up of glaucoma with high myopia, more attention need to be focused on structure and functional defects in macular areas.

Stereotactic laser interstitial thermal therapy for epilepsy associated with solitary and multiple cerebral cavernous malformations.

OBJECTIVE: The authors sought to perform a preliminary assessment of the safety and effectiveness of stereotactic laser interstitial thermal therapy (LITT) for patients with cerebral cavernous malformation (CCM)-related epilepsy. METHODS: The authors retrospectively analyzed 6 patients with CCM-related epilepsy who underwent LITT. Pre-, intra-, and postoperative brain MRI studies were used to characterize preoperative CCM volume, ablation volume, and postablation hemosiderin volume. Clinical outcomes were assessed postoperatively during clinic follow-up visits or phone interviews. RESULTS: LITT was performed in 7 CCMs in 6 patients. Two patients had familial CCM disease with multifocal lesions. Four treated CCMs were extratemporal, and 3 were in or near the visual pathways. The median follow-up was 25 (range 12-39) months. Five of 6 (83%) patients achieved seizure freedom (Engel I classification), of whom 4 (67%) were Engel IA and 1 was Engel IC after a single seizure on postoperative day 4. The remaining patient had rare seizures (Engel II). One patient had a nondisabling visual field deficit. There were no hemorrhagic complications. All patients were discharged within 24 hours postablation. MRI 3-11 months after ablation demonstrated expected focal necrosis and trace hemosiderin-related T2 hypointensity measuring 9%-44% (median 24%) of the original lesion volume, with significant (p = 0.04) volume reduction. CONCLUSIONS: LITT is a minimally invasive option for treating CCM-related epilepsy with seizure outcomes comparable to those achieved with open lesionectomy. The precision of LITT allows for the obliteration of eloquent, deep, small, and multifocal lesions with low complication rates, minimal postoperative discomfort, and short hospital stays. In this study the feasibility and benefits of this method were demonstrated in 2 patients with multifocal lesions.

Central 10-degree visual field change following non-penetrating deep sclerectomy in severe and end-stage glaucoma: preliminary results.

PURPOSE: To report the impact of non-penetrating deep sclerectomy (NPDS) in severe and end-stage glaucoma treatment on the central 10° visual field progression (mean deviation, four central points, foveal threshold) and assess the risk of sudden visual loss. METHODS: Monocenter database study. We reviewed records of 34 eyes with severe or end-stage glaucoma that underwent NPDS between 2009 and 2015, at the National Ophthalmology Center of XV-XX (Paris, France). Severe and end-stage glaucoma were defined according to the Bascom Palmer Modified Glaucoma Staging System classification. All eyes had a constricted visual field < 10° (severe injury by the Humphrey visual field automated (HVFA) 10-2). Visual fields were recorded every 6 months after the procedure. Data from the last visit was used for the statistical analysis. RESULTS: The mean follow-up duration was 29 months (range 6 to 54) and 33 (97%) eyes were followed for more than 1 year. There were no cases of postoperative sudden visual loss. The intraocular pressure (IOP) decreased from 21.9 ± 8.1 to 15.0 ± 5.4 mmHg (P < .001). Twenty-eight (82%) eyes had an IOP < 21 mmHg and 19 (56%) an IOP < 16 mmHg. The MD 10-2 remained stable (- 19.8 ± 7.4 to - 19.4 ± 8.1 dB, non-significant improvement of + 0.4 dB, P = .1). The MD 10-2 slope showed an insignificant improvement of + 0.25 ± 1.8 dB per year (dB/y) (P = 0.1), but this slope was significantly better when the IOP was reduced to < 16 mmHg than when the IOP was ≥ 16 mmHg at the last visit (+ 0.84  1.2 versus - 0.48 ± 2.2 dB/y, P = .05). The mean number of the four central test points with sensitivity ≤ 5 dB and the change in mean sensitivity of the four central field points remained stable. There were no significant changes in the VFI (from 25.4% ± 13 to 25.8% ± 20) and in foveal threshold. CONCLUSION: NPDS appears to provide stability of the central 10° visual field (with a trend towards improvement but non-significant) with no occurrence of "wipe-out" phenomenon and few other complications. Consideration of NPDS in end-stage and severe glaucoma is advisable given its low risk of complications and its considerable IOP decrease with a relative stability of the central visual field.

Correlation of macular structure and function in a boy with primary foveomacular retinitis and sequence of changes over 5 years.

PURPOSE: To describe the clinical characteristics, macular structure and function, and to document sequential changes over 5 years in a 10-year-old boy with bilateral primary foveomacular retinitis. METHODS: A 10-year-old boy presented with sudden onset scotoma in both eyes, experienced after getting up from bed on a non-eclipse day. He persistently denied direct sun-gazing. He neither had any significant systemic illness, nor was using any medications. In addition to a detailed examination at presentation that included fundus fluorescein angiogram (FFA), electroretinogram (ERG), pattern ERG and electrooculogram (EOG), he was examined periodically for 5 years with Humphrey visual field (HVF), spectral domain optical coherence tomogram (SDOCT), Amsler grid charting and multifocal ERG. The macular structure and functions were analyzed over the years and correlated with the symptoms. RESULTS: All findings were bilaterally symmetrical at each visit. At presentation, his corrected visual acuity was 20/25 with subfoveal yellow dot similar to solar retinopathy, central scotoma with reduced foveal threshold in HVF 24-2, micropsia in Amsler grid, missing of two plates on Ishihara color vision chart, transfoveal full thickness hyper-reflective band on SD OCT, unremarkable FFA and normal foveal peak in mfERG. The flash ERG and EOG were unremarkable. A month later, his VA improved to 20/20, he had relative scotoma in Amsler grid, no scotoma in HVF (10-2), restoration of the inner segment of the photoreceptors with sharp defect involving ellipsoid and photoreceptor interdigitation zone in SDOCT and blunting of foveal peaks in mfERG. Three months later, his corrected VA was 20/20 with relative scotoma in Amsler grid, normal color vision, no scotoma in HVF 10-2 and unchanged SDOCT findings. In subsequent examinations at 6, 9, 14, 29, 39 and 60 months, he was symptomless with VA 20/20, unremarkable fundus, normal Amsler grid and HVF (normal foveal threshold), unchanged SDOCT findings and the reduced foveal peaks on mfERG in both eyes got normalized only at 60 months. CONCLUSION: Presented here is a case of bilaterally symmetrical idiopathic foveomacular retinitis that had a clinical appearance similar to solar retinopathy. The fundus changes persisted for 4 weeks, the symptoms and changes in Amsler grid lasted for 3 months, and the foveal threshold in visual fields normalized within 3 months. Maximum change in the SDOCT defect occurred within a month, and the extrafoveal defect in the ellipsoid and photoreceptor interdigitation line persisted despite resolution of symptoms and resolution of the visual field defect and normal distance vision. Probably, the foveal lesion detected on SDOCT was too small to cause a reduction in the distance visual acuity or show up in the visual field and mfERG later.

A comparison of Goldmann III, V and spatially equated test stimuli in visual field testing: the importance of complete and partial spatial summation.

PURPOSE: Goldmann size V (GV) test stimuli are less variable with a greater dynamic range and have been proposed for measuring contrast sensitivity instead of size III (GIII). Since GIII and GV operate within partial summation, we hypothesise that actual GV (aGV) thresholds could predict GIII (pGIII) thresholds, facilitating comparisons between actual GIII (aGIII) thresholds with pGIII thresholds derived from smaller GV variances. We test the suitability of GV for detecting visual field (VF) loss in patients with early glaucoma, and examine eccentricity-dependent effects of number and depth of defects. We also hypothesise that stimuli operating within complete spatial summation ('spatially equated stimuli') would detect more and deeper defects. METHODS: Sixty normal subjects and 20 glaucoma patients underwent VF testing on the Humphrey Field Analyzer using GI-V sized stimuli on the 30-2 test grid in full threshold mode. Point-wise partial summation slope values were generated from GI-V thresholds, and we subsequently derived pGIII thresholds using aGV. Difference plots between actual GIII (aGIII) and pGIII thresholds were used to compare the amount of discordance. In glaucoma patients, the number of 'events' (points below the 95% lower limit of normal), defect depth and global indices were compared between stimuli. RESULTS: 90.5% of pGIII and aGIII points were within ±3 dB of each other in normal subjects. In the glaucoma cohort, there was less concordance (63.2% within ±3 dB), decreasing with increasing eccentricity. GIII found more defects compared to GV-derived thresholds, but only at outermost test locations. Greater defect depth was found using aGIII compared to aGV and pGIII, which increased with eccentricity. Global indices revealed more severe loss when using GIII compared to GV. Spatially equated stimuli detected the greatest number of 'events' and largest defect depth. CONCLUSIONS: Whilst GV may be used to reliably predict GIII values in normal subjects, there was less concordance in glaucoma patients. Similarities in 'event' detection and defect depth in the central VF were consistent with the fact that GIII and GV operate within partial summation in this region. Eccentricity-dependent effects in 'events' and defect depth were congruent with changes in spatial summation across the VF and the increase in critical area with disease. The spatially equated test stimuli showed the greatest number of defective locations and larger sensitivity loss.

Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma.

Aim and background: Automated perimetry plays an important role in the diagnosis and monitoring of glaucoma patients. The purpose of this study is to prospectively determine parity between Humphrey visual field analyzer (HVFA) perimetry (the current gold standard) and the VisuALL virtual reality perimeter (VRP). Materials and methods: In this prospective fully paired diagnostic accuracy study, patients with stable, long-term HVFA visual fields (horizontal dots for ≥4 consecutive visits on progression analysis) with preperimetric, mild, moderate, or severe visual field loss were familiarized with the VRP and then tested using its proprietary software. These results were used for point-by-point comparison with a contemporaneous HVFA test. This study was approved by the Institutional Review Board (IRB) of the University of the Incarnate Word, San Antonio, Texas, United States of America (IRB approval #20-06-002). Results: The prospective study analyzed 43 eyes of 24 glaucoma patients. Spearman's correlation of mean deviation (MD) revealed a strong correlation between HVFA and VRP with rs(41) = 0.871, p < 0.001. The overall mean difference in locus-locus sensitivity between the devices was -0.4 ± 1.5 dB but varied for different visual field locations and glaucoma severity. Conclusion: The parity between the VRP and HVFA was remarkably strong for mild and moderate glaucoma. Given its portability, ease of use, space efficiency, and low cost, the VRP presents a viable alternative. Clinical significance: Automated perimetry, specifically the HVFA, has been the gold standard for visual field assessment since its introduction. The recent COVID-19 pandemic has illuminated the advantages of the VRP, allowing for safer visual assessment for both patient and clinician alike. Our study hopes to establish parity between these systems, allowing for the efficient integration of a novel head-mounted perimetry system that can safely diagnose and monitor glaucomatous progression in clinical practice. Precis: Investigation of parity between Olleyes VisuALL virtual reality perimetry (VRP) and existing standard HVFA perimetry is essential to the diagnosis and management of glaucoma. Linear correlations between the two were established from 43 glaucomatous eyes. Parity was strong for mild and moderate glaucoma, presenting VRP as a viable alternative. How to cite this article: Griffin JM, Slagle GT, Vu TA, et al. Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma. J Curr Glaucoma Pract 2024;18(1):4-9.

Hidden blind spot and pseudofixation loss.

Background: Correct mapping of the blind spot is important, as it serves as an estimate of fixation reliability. When the blind spot is not seen in the expected location in Humphrey visual field (HVF) printout, the clinician should give a thought to why this might be the case. Purpose: This video describes a series of cases, in which due to different reasons the blind spot could not be seen in the presumed expected location in the grayscale and numeric data of the HVF printout and the possible explanation behind this. Synopsis: When interpreting perimetry results, it is important to know whether the field test is reliable or not. A stimulus presented at the location of physiologic blind spot should not be seen by a patient with a steady fixation in Heijl-Krakau method. Responses will also occur, however, if the patient has a tendency for false-positive responses, or when the blind spot of the properly fixing eye is not in the location where the test stimulus is presented, because of anatomic variation, or if the patient's head is tilted while performing the test. Highlights: Perimetrist should recognize these potential artifact, during the test and relocate the blind spot. In case, such results are seen after finishing the test, it is recommended for the clinician to repeat the test. Video link: https://youtu.be/I1gxmMWqDQA.

High false-positive response in perimetry.

Background: In Humphrey visual field analyzer, the false-positive (FP) responses imply that the patient has pressed the response button despite no stimulus being seen at the time of response and FP rates >15% are flagged. The classical "Trigger happy" visual field has increased fixation loss, very high threshold retinal sensitivity with the values in supernormal range, "white scotoma" on grayscale map, high positive mean deviation (MD), glaucoma hemifield test (GHT) gives classification of "abnormally high sensitivity, 'Excessive high false positive' message is displayed," and pattern deviation probability plot has more defects than total deviation probability plot known as "reverse cataract pattern." However, these classical findings are not seen in all the cases of FP as the same thumb rule cannot be applied to all the visual fields with high FP. Purpose: This video emphasizes the significance of careful examination of all the parameters in a visual field printout of high FP to interpret the test results and the caution needed when an FP response is seen in a patient with advanced glaucoma. Synopsis: The video presents some interesting visual fields in normal and glaucoma patients and the effect of high FP responses on MD, the different classification messages displayed for GHT, patterns of total deviation probability plot and pattern deviation probability plot, and how to identify the hidden FP. Highlights: This video highlights the importance of careful examination of all the parameters in a visual field printout to interpret the test results. One should be especially cautious when an FP response is noted in a patient with advanced glaucoma, as the retinal sensitivity values may not be in supernormal range but are significantly affected by the increased FP. Clinician should be able to identify this and repeat the test as high FP reponses can lead to underestimation of visual field loss. Video link: https://youtu.be/T2SGZf16UzA.

Comparison of the effect of audiovisual and verbal instructions on patient performance while performing automated Humphrey visual field testing.

Purpose: To compare the effect of audiovisual and verbal instructions on patient performance while performing automated Humphrey visual field testing. Methods: This was a prospective study. A total 120 patients divided into groups of 40 each were recruited from the glaucoma outpatient department (OPD). All patients were aged 35-75 years with no previous experience of performing HFA. Patients with hearing impairment, any other cognitive impairment, and best-corrected visual acuity (BCVA) ≤6/36 on Snellen's visual acuity were excluded. The first two groups were given strict (conservative) and lenient (liberal) verbal instructions. The instructions were adapted from those listed in the manufacturer's instruction. and the third group was shown a standard video depicting in detail how perimetry was to be performed. A questionnaire was given to each patient before and after the test to assess the patient's performance. Results: Patients diagnosed with glaucoma during testing in each group were 29 (72.50%), 30 (75.0%), and 33 (82.5%) in the video instructed, strictly verbal, and leniently verbal groups, respectively. The overall mean deviation (MD) in the right eye (RE) was of - 3.38 (-4.9 to 1.9) and in the left eye (LE) was - 3.96 (-6.4 to - 1.9). Reliable field was slightly higher for the video instructed group (47.5%) and lowest for the strictly verbal group (22.5%) (P = 0.033). A higher number of patients were very motivated in the video instructed group (27%) (P = 0.041). Post-test questionnaires showed that 40% of patients felt they have performed the test with 100% accuracy in video group with less guessing. A higher number of patients in the video instructed group (85%) felt instruction was helpful in performing the test (P = 0.001). Conclusion: The video groups were more motivated and had better confidence to perform the test with less anxiety and stress and with probably better understanding of the procedure due to visual effects enhancing their understanding.

Visual field changes in glaucoma patients after blepharoptosis surgery.

PURPOSE: To examine changes in parameters of the visual field test before and after blepharoptosis surgery in patients with glaucoma. METHODS: Twenty-three eyes of 14 glaucoma patients who underwent blepharoptosis surgery at Toyama University Hospital between July 2015 and September 2020 were included in this study. Pre- and post-operative values for the mean deviation (MD), pattern standard deviation (PSD) and total deviation (TD) of the upper or lower hemi-visual field in the Humphrey visual field test, best-corrected visual acuity (BCVA), intraocular pressure (IOP), and margin reflex distance (MRD)-1 were compared. RESULTS: MRD-1 showed a significant improvement after blepharoptosis surgery (preoperative MRD-1: 1.0 ± 0.82 mm, postoperative MRD-1: 3.26 ± 0.66 mm, p < 0.001). There were no significant differences in BCVA, IOP, MD and PSD values before and after surgery. On the other hand, there was a significant improvement in the superior TD (preoperative: -11.29 ± 6.57 dB, postoperative: -9.88 ± 7.31 dB, p = 0.044) although no significant difference was detected in the inferior TD postoperatively. The preoperative parameters of 2 groups (improvement and non-improvement groups of postoperative superior TD) were compared. Preoperative MD and superior TD were significantly lower in the improvement group (p = 0.03, p = 0.004, respectively), although there was no significant difference in preoperative PSD and inferior TD between the two groups. CONCLUSION: In glaucoma patients, blepharoptosis may interfere with accurate visual field assessment, especially of superior TD.

Virtual Reality Oculokinetic Perimetry Test Reproducibility and Relationship to Conventional Perimetry and OCT.

Purpose: Vivid Vision Perimetry (VVP; Vivid Vision, Inc) is a novel method for performing in-office and home-based visual field assessment using a virtual reality platform and oculokinetic perimetry. Here we examine the reproducibility of VVP Swift and compare results with conventional standard automated perimetry (SAP) and spectral-domain (SD) OCT. Design: Cross-sectional study. Participants: Fourteen eyes of 7 patients with open-angle glaucoma (OAG) (average age, 64.6 years; 29% women) and 10 eyes of 5 patients with suspected glaucoma (average age, 61.8 years; 40% women) were enrolled. Methods: Patients with OAG and suspected glaucoma were enrolled prospectively and underwent 2 VVP Swift examinations. Results were compared with 1 conventional SAP examination (Humphrey Visual Field [HVF]; Zeiss) and 1 SD OCT examination. Main Outcome Measures: Mean sensitivity (in decibels) obtained for each eye in 2 VVP Swift test sessions and a conventional SAP examination, thickness of the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) for the SD OCT examination, and mean test durations of the VVP Swift and SAP examinations. Results: The mean test duration of VVP Swift in both eyes (8.5 minutes) was significantly shorter (P < 0.001) than SAP (12.2 minutes). The average absolute difference of the mean sensitivity between the 2 VVP Swift sessions was found to be 0.73 dB (95% confidence interval [CI], 0.40-1.06). A statistically significant association was found between average mean sensitivity measurements from the VVP and mean deviation (MD) measurements obtained by the HVF with a Pearson correlation coefficient of 0.86 (95% CI, 0.70-0.94; P < 0.001). Mean visual sensitivity measurements from the VVP Swift test were significantly associated with average RNFL thickness (r = 0.66; P = 0.014) and GCC thickness (r = 0.63; P = 0.02), whereas the correlation coefficients between HVF MD and RNFL and GCC were 0.86 (P < 0.001) and 0.83 (P < 0.001), respectively. Conclusions: Our results demonstrated that the VVP Swift test can generate reproducible results and is comparable with conventional SAP. This suggests that the device can be used by clinicians to assess visual function in glaucoma.

Genetic Risk of Cardiovascular Disease Is Associated with Macular Ganglion Cell-Inner Plexiform Layer Thinning in an Early Glaucoma Cohort.

Purpose: To evaluate the association between genetic risk for cardiovascular disease and retinal thinning in early glaucoma. Design: Prospective, observational genetic association study. Participants: Multicohort study combining a cohort of patients with suspect and early manifest primary open-angle glaucoma (POAG), a cohort of patients with perimetric POAG, and an external normative control cohort. Methods: A cardiovascular disease genetic risk score was calculated for 828 participants from the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study. Participants were characterized as showing either predominantly macular ganglion cell-inner plexiform layer (GCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL) or equivalent macular GCIPL and pRNFL spectral-domain OCT thinning. The cardiovascular disease genetic risk scores for these groups were compared to an internal reference group of stable suspected glaucoma and of an external normative population. Replication was undertaken by comparing the phenotypes of participants from the Australia New Zealand Registry of Advanced Glaucoma (ANZRAG) with the normative control group. Main Outcome Measures: Spectral-domain OCT and Humphrey Visual Field (HVF) change. Results: After accounting for age, sex, and intraocular pressure (IOP), participants with predominantly macular GCIPL thinning showed a higher cardiovascular disease genetic risk score than reference participants (odds ratio [OR], 1.76/standard deviation [SD]; 95% confidence interval [CI], 1.18-2.62; P = 0.005) and than normative participants (OR, 1.32/SD; 95% CI, 1.12-1.54; P = 0.002). This finding was replicated by comparing ANZRAG participants with predominantly macular GCIPL change with the normative population (OR, 1.39/SD; 95% CI, 1.05-1.83; P = 0.022). Review of HVF data identified that participants with paracentral visual field defects also demonstrated a higher cardiovascular disease genetic risk score than reference participants (OR, 1.85/SD; 95% CI, 1.16-2.97; P = 0.010). Participants with predominantly macular GCIPL thinning exhibited a higher vertical cup-to-disc ratio genetic risk score (OR, 1.48/SD; 95% CI, 1.24-1.76; P < 0.001), but an IOP genetic risk score (OR, 1.12/SD; 95% CI, 0.95-1.33; P = 0.179) comparable with that of the normative population. Conclusions: This study highlighted the relationship between cardiovascular disease and retinal thinning in suspect and manifest glaucoma cases.

The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma.

Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell-inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (ß = -0.13 µm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; ß = -0.20 µm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 µm vs. 71.9 µm; P = 0.011) and pRNFL (77.6 µm vs. 79.2 µm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.

Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial.

Purpose: To evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes. Design: Double-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365). Participants: Sixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo. Methods: Macular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit. Main Outcome Measures: Change in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months. Results: A mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial. Conclusions: Macular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.

A Novel Method of Visual Field Assessment for Patients with Unilateral Severely Limited Central Vision: A Pilot Study.

PURPOSE: Reliable visual field testing requires the tested eye to be fixated on a central target. This poses a major obstacle for eyes with severe central vision loss. This pilot study assesses whether it may be feasible to examine such patients with a modified method. METHODS: A green filter was placed over the fellow eye. A FASTPAC algorithm was used with a red stimulus. The green filter prevented transmission of the red stimuli but allowed visualization of the yellow fixation light. Subjects were tested by both the conventional and the novel method, performed in a randomized order. We compared the reliability indices and also the precision of the two methods. RESULTS: We present results from six patients. The novel method was associated with an 85% reduction in fixation losses (P=0.028) and a 58% reduction in eye motion on gaze tracking (P=0.007). Further, specialized testing in one of the volunteers demonstrated that the novel technique could more precisely define a small zone of preserved peripheral vision (P=0.008). CONCLUSION: The results of this pilot study suggest that the novel method described may be a feasible strategy for visual field testing in patients with unilateral severe central vision loss.

How Many Subjects are Needed for a Visual Field Normative Database? A Comparison of Ground Truth and Bootstrapped Statistics.

PURPOSE: The number of subjects needed to establish the normative limits for visual field (VF) testing is not known. Using bootstrap resampling, we determined whether the ground truth mean, distribution limits, and standard deviation (SD) could be approximated using different set size (x) levels, in order to provide guidance for the number of healthy subjects required to obtain robust VF normative data. METHODS: We analyzed the 500 Humphrey Field Analyzer (HFA) SITA-Standard results of 116 healthy subjects and 100 HFA full threshold results of 100 psychophysically experienced healthy subjects. These VFs were resampled (bootstrapped) to determine mean sensitivity, distribution limits (5th and 95th percentiles), and SD for different 'x' and numbers of resamples. We also used the VF results of 122 glaucoma patients to determine the performance of ground truth and bootstrapped results in identifying and quantifying VF defects. RESULTS: An x of 150 (for SITA-Standard) and 60 (for full threshold) produced bootstrapped descriptive statistics that were no longer different to the original distribution limits and SD. Removing outliers produced similar results. Differences between original and bootstrapped limits in detecting glaucomatous defects were minimized at x = 250. CONCLUSIONS: Ground truth statistics of VF sensitivities could be approximated using set sizes that are significantly smaller than the original cohort. Outlier removal facilitates the use of Gaussian statistics and does not significantly affect the distribution limits. TRANSLATIONAL RELEVANCE: We provide guidance for choosing the cohort size for different levels of error when performing normative comparisons with glaucoma patients.