Purpose Existing summary statistics based upon optical coherence tomography (OCT) scans and/or visual fields (VF) are suboptimal for distinguishing between healthy and glaucomatous eyes in the clinic. This study evaluates the extent to which a hybrid deep learning method (HDLM), combined with a single wide-field OCT protocol, can distinguish eyes previously classified as either healthy suspects or mild glaucoma. Patients and Methods 102 eyes from 102 patients, with or suspected open-angle glaucoma, had previously been classified by two glaucoma experts as either glaucomatous (57 eyes) or healthy/suspects (45 eyes). The HDLM had access only to information from a single, wide-field (9×12mm) swept-source OCT scan per patient. Convolutional neural networks were used to extract rich features from maps derived from these scans. Random forest classifier was used to train a model based on these features to predict the existence of glaucomatous damage. The algorithm was compared against traditional OCT and VF metrics. Results The accuracy of the HDLM ranged from 63.7% to 93.1% depending upon the input map. The RNFL probability map had the best accuracy (93.1%), with 4 false positives, and 3 false negatives. In comparison, the accuracy of the OCT and 24-2 and 10-2 VF metrics ranged from 66.7% to 87.3%. The OCT quadrants analysis had the best accuracy (87.3%) of the metrics, with 4 FP and 9 FN. Conclusion The HDLM protocol outperforms standard OCT and VF clinical metrics in distinguishing healthy suspect eyes from eyes with early glaucoma. It should be possible to further improve this algorithm and with improvement it might be useful for screening

IMPORTANCE Recent evidence supports the presence of macular damage (within 8°of the central field) to retinal ganglion cells and associated central visual field (VF) defects in glaucoma, even in early stages. Despite this, to our knowledge, the association of 10-2 VF damage with vision-related quality of life (QOL) has not been well studied.OBJECTIVE To determine the association between QOL and visual function as measured by 24-2 and 10-2 VFs in patients with primary open-angle glaucoma and to test the hypothesis that patients with vision-related QOL disproportionate to their 24-2 VF status may exhibit 10-2 damage overlooked by the 24-2 test. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional analysis of observational cohort study data taken from a tertiary care specialty practice, 113 patients with glaucoma with the entire range of 24-2 VF damage completed the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

PurposeTo evaluate a report for glaucoma diagnosis based on a single optical coherence tomography (OCT) protocol.MethodsA wide-field (9 × 12 mm) swept-source (SS) OCT scan, encompassing the macula and disc, was obtained on 130 eyes (patients) with or suspected open-angle glaucoma, a mean deviation greater than or equal to −6 dB on a 24-2 visual field (VF), and spherical refractive error between ± 6 diopters (D). The single-page report contained a circumpapillary retinal nerve fiber layer (cpRNFL) thickness plot; retinal ganglion cell layer and retinal nerve fiber layer (RNFL) thickness and probability plots of the macula and optic nerve; and an enface slab image of the optic nerve. A report specialist judged each eye as healthy (H); probably healthy (PH); forced-choice healthy (FC-H); optic neuropathy (ON); probably ON (PON); forced-choice optic neuropathy (FC-ON). Two glaucoma specialists made similar judgments about the presence of glaucomatous damage. The glaucoma specialists had 24-2 and 10-2 VFs, fundus photos, patient chart information, and the single-page report including the report specialist's interpretation.ResultsThe reference standard consisted of 57 eyes judged as glaucomatous (ON or PON) and 45 eyes judged as healthy (H or PH) by both glaucoma specialists. The report specialist identified 56 of the glaucomatous eyes as optic neuropathy (i.e., ON, PON, or FC-ON), and 44 of the healthy eyes as healthy (i.e., H, PH, or FC-H), an accuracy of 98.0%.ConclusionsA single-page report based upon a single, wide-field OCT scan has the information needed to diagnose early glaucoma with excellent sensitivity/specificity.Translational RelevanceIt is possible that screening for glaucoma can be effective with only a single OCT protocol.

IMPORTANCEThe Tube vs Trabeculectomy Trial (TVT) found that the 350-mm 2 Baerveldt implant (tube) and trabeculectomy with mitomycin may be similarly effective in lowering intraocular pressure in primary open-angle glaucoma. However, to date, there are no published long-term clinical data on the cost-effectiveness of trabeculectomy with mitomycin vs tube insertion.OBJECTIVE To assess the cost-effectiveness of these procedures compared with maximal medical treatment. DESIGN, SETTING, AND PARTICIPANTSWe used the Markov cohort model with a 5-year time horizon to study a hypothetical cohort of 100 000 patients who required glaucoma surgery. MAIN OUTCOMES AND MEASURESQuality-adjusted life-years (QALYs) gained, costs from the societal perspective, and the incremental cost-effectiveness ratio of medical treatment, trabeculectomy, and tube insertion. Costs were identified from Medicare Current Procedural Terminology and Ambulatory Payment Classification reimbursement codes and Red Book medication costs. The QALYs were based on visual field and visual acuity outcomes. The hypothetical societal limit to resources was included using a willingness-to-pay threshold of $50 000 per QALY. Costs and utilities were discounted at 3% per year. Uncertainty was assessed using deterministic sensitivity analyses.

PurposeTo assess the agreement between structural (optical coherence tomography [OCT]) and functional (visual field [VF]) glaucomatous damage with an automated method and deviation/probability maps, and to compare this method to a metric method.MethodsWide-field spectral-domain OCT scans, including the disc and macula, and 24-2 and 10-2 VFs were obtained from 45 healthy control (H) eyes/individuals, and 53 eyes/patients with 24-2 mean deviation (MD) better than −6 dB diagnosed as “definite glaucoma” (DG) by experts. Abnormal structure–abnormal function (aS-aF) agreement was assessed with an automated topographic (T) method based upon VF pattern deviation and OCT probability maps. Results were compared to a metric (M) method optimized for accuracy, (abnormal 24-2 glaucoma hemifield test [GHT] or pattern standard deviation [PSD], or 10-2 PSD AND abnormal OCT [quadrant]).ResultsFor the T-method, 47 (88.7%) of the 53 DG eyes showed aS-aF agreement, compared to 2 (4.5%) of the 45 H eyes. The aS-aF agreement for these two H eyes was easily identified as mistaken, and did not replicate on a subsequent test. Without the 10-2, the aS-aF agreement decreased from 47 to 34 (64.2%) of 53 DG eyes. For the M-method, 37 (69.8%) of the 53 DG eyes showed aS-aF agreement, while omitting the 10-2 VF resulted in agreement in only 33 (62.3%) eyes.ConclusionsThere is good agreement between structural and functional damage, even in eyes with confirmed early glaucomatous damage, if both 24-2 and 10-2 VFs are obtained, and abnormal locations on the VFs are compared to abnormal regions seen on OCT macular and disc scans. This can be done in an objective, automated fashion. (ClinicalTrials.gov number, NCT02547740.)

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IMPORTANCE Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial function and energy production may enhance retinal ganglion cell survival in animal models of glaucoma, but there is scant information on its effectiveness in a clinical setting.OBJECTIVE To test the hypothesis that a combination of nicotinamide and pyruvate can improve retinal ganglion cell function in human glaucoma as measured with standard automated perimetry.DESIGN, SETTING, AND PARTICIPANTS In this phase 2, randomized, double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients were assessed for eligibility. Of these, 42 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized. A total of 32 completed the study and were included in the final analysis. The mean (SD) age was 64.6 (9.8) years. Twenty-one participants (66%) were female. Participant race and ethnicity data were collected via self-report to ensure the distribution reflected that observed in clinical practice in the US but are not reported here to protect patient privacy. Recruitment took place in April 2019 and patients were monitored through December 2020. Data were analyzed from January to May 2021.INTERVENTIONS Ascending oral doses of nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) vs placebo (2:1 randomization). MAIN OUTCOMES AND MEASURESNumber of visual field test locations improving beyond normal variability in the study eye. Secondary end points were the rates of change of visual field global indices (mean deviation [MD], pattern standard deviation [PSD], and visual field index [VFI]).RESULTS Twenty-two of 29 participants (76%) randomized to the intervention group and 12 of 13 participants (92%) randomized to placebo received their allocation, and 32 participants (32 eyes; ratio 21:11) completed the study (21 from the intervention group and 11 from the placebo group). Median (IQR) follow-up time was 2.2 (2.0-2.4) months. No serious adverse events were reported during the study. The number of improving test locations was significantly higher in the treatment group than in the placebo group (median [IQR], 15 [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] vs 7 [6-11]; P = .005). Rates of change of PSD suggested improvement with treatment compared with placebo (median, −0.06 vs 0.02 dB per week; 95% CI, 0.02 to 0.24; P = .02) but not MD (0.04 vs −0.002 dB per week; 95% CI, −0.27 to 0.09; P = .35) or VFI (0.09 vs −0.02% per week; 95% CI, −0.53 to 0.36; P = .71). CONCLUSIONS AND RELEVANCEA combination of nicotinamide and pyruvate yielded significant short-term improvement in visual function, supporting prior experimental research suggesting a role for these agents in neuroprotection for individuals with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression.

Purpose Besides glia-driven neuroinflammation, growing evidence from analysis of human blood samples, isolated autoantibodies, and postmortem tissues also support systemic immune responses during neurodegeneration in glaucoma patients. To explore the T-cell–mediated component of systemic immunity, this study analyzed T lymphocytes in patients' blood. Methods Blood samples were collected from 32 patients with glaucoma and 21 nonglaucomatous controls, and mononuclear cells were isolated by Histopaque density gradient centrifugation. T-cell subset distribution was analyzed by multicolor flow cytometry after helper (Th) and cytotoxic fractions, and Th subpopulations, were stained with antibodies to CD4, CD8, or distinctive markers, such as IFN-γ (for Th1), IL-4 (for Th2), IL-17A (for Th17), and CD25/FoxP3 (for T regulatory cells [Tregs]). In addition, proliferative activity and cytokine secretion of T cells were analyzed after in vitro stimulation. Results Analysis of T-cell subset distribution detected a glaucoma-related shift. Despite similar frequencies of CD4+ or CD8+ T cells, or Th1, Th2, or Th17 subsets in glaucoma and control groups, glaucomatous samples exhibited a trend toward decreased frequency of CD4+ (or CD8+)/CD25+/FoxP3+ Tregs within the entire CD4+ (or CD8+) population ( P < 0.001). Furthermore, CD4+ T cells in glaucomatous samples presented a greater stimulation response (∼3-fold) as characterized by increased proliferation and proinflammatory cytokine secretion ( P < 0.05). Conclusions These findings suggest that the immunity activated in glaucoma may not be counterbalanced by an efficient immune suppression. More work is encouraged to determine whether shifted T-cell homeostasis may contribute to neurodegeneration in glaucoma, and/or whether T-cell subset imbalance may serve as a biomarker of autoimmune susceptibility.