Evaluating the Accuracy of ChatGPT and Google BARD in Fielding Oculoplastic Patient Queries: A Comparative Study on Artificial versus Human Intelligence.

PURPOSE: This study evaluates and compares the accuracy of responses from 2 artificial intelligence platforms to patients' oculoplastics-related questions. METHODS: Questions directed toward oculoplastic surgeons were collected, rephrased, and input independently into ChatGPT-3.5 and BARD chatbots, using the prompt: "As an oculoplastic surgeon, how can I respond to my patient's question?." Responses were independently evaluated by 4 experienced oculoplastic specialists as comprehensive, correct but inadequate, mixed correct and incorrect/outdated data, and completely incorrect. Additionally, the empathy level, length, and automated readability index of the responses were assessed. RESULTS: A total of 112 patient questions underwent evaluation. The rates of comprehensive, correct but inadequate, mixed, and completely incorrect answers for ChatGPT were 71.4%, 12.9%, 10.5%, and 5.1%, respectively, compared with 53.1%, 18.3%, 18.1%, and 10.5%, respectively, for BARD. ChatGPT showed more empathy (48.9%) than BARD (13.2%). All graders found that ChatGPT outperformed BARD in question categories of postoperative healing, medical eye conditions, and medications. Categorizing questions by anatomy, ChatGPT excelled in answering lacrimal questions (83.8%), while BARD performed best in the eyelid group (60.4%). ChatGPT's answers were longer and potentially more challenging to comprehend than BARD's. CONCLUSION: This study emphasizes the promising role of artificial intelligence-powered chatbots in oculoplastic patient education and support. With continued development, these chatbots may potentially assist physicians and offer patients accurate information, ultimately contributing to improved patient care while alleviating surgeon burnout. However, it is crucial to highlight that artificial intelligence may be good at answering questions, but physician oversight remains essential to ensure the highest standard of care and address complex medical cases.

Macula structural and vascular differences in glaucoma eyes with and without high axial myopia.

AIMS: To identify clinically relevant parameters for identifying glaucoma in highly myopic eyes, an investigation was conducted of the relationship between the thickness of various retinal layers and the superficial vessel density (sVD) of the macula with axial length (AL) and visual field mean deviation (VFMD). METHODS: 270 glaucoma patients (438 eyes) participating in the Diagnostic Innovations in Glaucoma cross-sectional study representing three axial myopia groups (non-myopia: n=163 eyes; mild myopia: n=218 eyes; high myopia (AL>26 mm): n=57 eyes) who completed macular optical coherence tomography (OCT) and OCT-angiography imaging were included. Associations of AL and VFMD with the thickness of the ganglion cell inner plexiform layer (GCIPL), macular retinal nerve fibre layer (mRNFL), ganglion cell complex (GCC), macular choroidal thickness (mCT) and sVD were evaluated. RESULTS: Thinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=34.5% and R2=32.9%; respectively p<0.001), but not with AL (all p>0.1). Thicker mRNFL showed a weak association with increasing AL (R2=2.4%; p=0.005) and a positive association with VFMD (global R2=19.2%; p<0.001). Lower sVD was weakly associated with increasing AL (R2=1.8%; p=0.028) and more strongly associated with more severe glaucoma VFMD (R2=29.6%; p<0.001). Thinner mCT was associated with increasing AL (R2=15.5% p<0.001) and not associated with VFMD (p=0.194). mRNFL was thickest while mCT was thinnest in all sectors of high myopic eyes. CONCLUSIONS: As thinner GCIPL and GCC were associated with increasing severity of glaucoma but were not significantly associated with AL, they may be useful for monitoring glaucoma in highly myopic eyes.

The Association Between Regional Macula Vessel Density and Central Visual Field Damage in Advanced Glaucoma Eyes.

PRCIS: Both macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma. PURPOSE: The purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes. METHODS: Macular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD) <-10 dB] were evaluated. Regional and global VF mean sensitivity (MS) was calculated from total deviation plots. Superficial and deep MVD were obtained from 3 × 3 and 6×6 mm 2 OCTA scans using 2 sectoral definitions. Spectral-domain optical coherence tomography macular GCC thickness was obtained simultaneously from the same scan as the MVD measurements. Linear regression models were used to assess the associations ( R2 ). RESULTS: Lower MS was significantly associated with a reduction in superficial MVD and GCC in each region of both scan sizes for both maps. Associations were weaker in the individual sectors of the whole image grid than the Early Treatment Diabetic Retinopathy Study map. Deep-layer MVD was not associated with central MS. Although 6×6 mm 2 and perifoveal vessel density had better associations with central 10-degree MS compared with GCC thickness (eg, R2 from 25.7 to 48.1 µm and 7.8% to 32.5%, respectively), GCC associations were stronger than MVD associations in the central 5-degree MS. CONCLUSIONS: Given a stronger MVD-central 10-degree VF association compared with GCC, as well as stronger GCC-central 5-degree VF association compared with MVD, MVD and GCC are complementary measurements in eyes with advanced glaucoma. A longitudinal analysis is needed to determine the relative utility of the GCC and MVD measurements.

Comparison of the Effects of Latanoprostene Bunod and Timolol on Retinal Blood Vessel Density: A Randomized Clinical Trial.

PURPOSE: To compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects. DESIGN: Randomized, single center, crossover clinical trial. METHODS: Eligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment. RESULTS: One eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all). CONCLUSIONS: Topical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

Macular Thickness and Microvasculature Loss in Glaucoma Suspect Eyes.

PURPOSE: To characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON). DESIGN: Prospective, longitudinal study. PARTICIPANTS: Eight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm1 GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model. MAIN OUTCOME MEASURES: Change rates of macula GCC thickness and superficial vessel density. RESULTS: Significant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 µm/year; P = 0.025) and GON group (-0.79 µm/year; P = 0.058) were faster than those of the healthy group (-0.11 µm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease. CONCLUSIONS: Whereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.

Agreement between Compass Fundus Perimeter New Grid and 10-2 Testing Protocols for Detecting Central Visual Field Defects.

PURPOSE: To evaluate the agreement between Compass New Grid (NG) and 10-2 test protocols for detecting early glaucomatous defects in the central 10 degrees of the visual field (CVFD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 123 eyes of 14 healthy individuals, 17 glaucoma suspects, and 32 glaucoma patients were enrolled. METHODS: Subjects performed NG and 10-2 Compass automated perimetry testing within 1 week. For both test protocols, total deviation (TD) and pattern deviation (PD) plot CVFDs were defined by 3 contiguous points with probabilities of <5%, <2%, <2% or <5%, <1%, <1%. Cohen's Kappa statistic was used to assess agreement between NG and 10-2 for identifying CVFDs. The Spectralis GMPE Hood Glaucoma Report (investigational software version) macula deviation analysis obtained within 1 year was used for calculating sensitivities and specificities of test protocols. MAIN OUTCOME MEASURES: Protocols' agreement, sensitivity, and specificity. RESULTS: Fair to moderate agreement was observed between NG and 10-2 protocols for detecting presence of superior CVFDs on TD (k = 0.57) and PD (k = 0.26) plots and for detecting inferior CVFDs on TD (0.49) and PD (0.27) plots. With the use of OCT macula deviation maps, specificity for detecting CVFD was consistently higher with NG than 10-2 tests for TD plots of the superior hemifield (0.82 and 0.65), inferior hemifield (0.92 and 0.84), and PD plots of the superior hemifield (0.81 and 0.36) and inferior hemifield (0.86 and 0.52). Sensitivity of NG was consistently lower than TD plots of the superior hemifield (0.48 and 0.72), inferior hemifield (0.28 and 0.46), and PD plots of the superior hemifield (0.48 and 0.78) and inferior hemifield (0.20 and 0.52). By using pattern standard deviation (PSD) criterion, the mean PSD values for 10-2 and NG VF tests were 1.61 (95% confidence interval [CI], 1.26-1.96) and 1.81 (95% CI, 1.45-2.17) (P < 0.001), respectively. CONCLUSIONS: Although the Compass NG detected fewer CVFDs than the 10-2 test protocol, it did detect CVFDs that were not observed in the Compass 24-2 test in patients with early glaucoma. Therefore, NG may be particularly useful in clinical situations when higher specificity is desired or PSD criterion is used.

Diurnal Variation of Retinal Vessel Density in Healthy Human Eyes.

PRECIS: A small increase in optic nerve head vessel density (VD), but not macular VD, in the evening compared with the morning is observed in healthy subjects. PURPOSE: To evaluate the diurnal variation of the macular and optic nerve head (ONH) VD in healthy eyes as measured with optical coherence tomography angiography (OCT-A). METHODS: In this prospective study of healthy individuals older than 18 years old, VD parameters, including macular whole image vessel density, parafoveal vessel density, ONH whole image vessel density, ONH whole image capillary density, circumpapillary vessel density (cpVD), and circumpapillary capillary density, were measured with OCT-A at 4 time points throughout the day (8 am, 12 pm, 4 pm, and 8 pm). RESULTS: Twenty-nine healthy eyes were included from 15 subjects (mean age: 30.9 y). After adjustment for age and mean ocular perfusion pressure, a significant positive rate of change was found for cpVD (0.05%/h; P=0.027). In contrast, macular VD changes were not significantly different. When comparing morning (8 am and 12 pm) and evening (4 pm and 8 pm) measurements, there were small, but statistically significant, increases for all ONH measurements. The greatest increase was found for cpVD (0.58%; P=0.022). Significant but small increases in mean arterial pressure and mean ocular perfusion pressure were also observed. CONCLUSIONS: There was a small increase in ONH VD, but not macular VD, in the evening compared with the morning in healthy human eyes. As the observed difference was within the measurement variability, our results suggest the timing of OCT-A examination does not affect retinal VD measurements.

Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PRECIS: Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma. PURPOSE: The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes. MATERIALS AND METHODS: Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups. RESULTS: Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001). CONCLUSIONS: SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.

OCT Angiography Artifacts in Glaucoma.

PURPOSE: To determine the prevalence of different types of artifacts seen in OCT angiography (OCTA) images of healthy and glaucoma eyes and evaluate the characteristics associated with poor-quality images. DESIGN: Retrospective study. PARTICIPANTS: A total of 649 eyes of 368 healthy, glaucoma suspect, and glaucoma patients. METHODS: Angiovue (Optovue Inc) high-density (HD) and non-HD optic nerve head and macula OCTA images of participants were evaluated by 4 expert reviewers for the presence of different artifacts, including eye movement, defocus, shadow, decentration, segmentation error, blink, and Z offset in the superficial vascular layer. Each OCTA scan was designated to have good or poor quality based on the presence of artifacts. The association of demographic and ocular characteristics with the likelihood of obtaining poor-quality OCTA images was evaluated. MAIN OUTCOME MEASURES: The prevalence of OCTA artifacts and the factors associated with increased likelihood of capturing poor-quality OCTA images. RESULTS: A total of 5263 OCTA images were evaluated. Overall, 33.9% of the OCTA images had poor quality. The majority of images with acceptable quality scores (QS ≥ 4) had no artifacts (76.6%). Other images had 1 (13.6%) or 2 or more artifacts (9.8%). Older age (P < 0.001), male gender (P = 0.045), worse visual field mean deviation (P < 0.001), absence of eye tracking (P < 0.001), and macular scan area (P < 0.001) were associated with a higher likelihood of obtaining poor-quality images. In images with acceptable QS, the commercially available quality measures including QS and signal strength index had the area under the receiver operating characteristic curves of 0.65 (95% confidence interval [CI], 0.62-0.69) and 0.70 (95% CI, 0.68-0.73) to detect good-quality images, respectively. CONCLUSIONS: OCTA artifacts associated with poor-quality images are frequent, and their prevalence is affected by ocular and patient characteristics. One should not rely solely on the quantitative assessments that are provided automatically by OCTA instruments. A systematic scan review should be conducted to ensure appropriate interpretation of OCTA images. Given the high prevalence of poor-quality OCTA images, the images should be reacquired whenever an apparent and correctable artifact is present on a captured image.

Comparison of Peripapillary Capillary Density in Glaucoma Patients of African and European Descent.

PURPOSE: To evaluate racial differences in optic nerve head peripapillary capillary density measured by OCT angiography (OCTA) in patients with open-angle glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Two hundred eighty-four eyes of 195 glaucoma patients and 108 eyes of 58 healthy participants from the Diagnostic Innovations in Glaucoma Study. METHODS: Global and sectoral circumpapillary capillary density (cpCD) loss in participants of European descent (ED) and African descent (AD) were compared. Areas under the receiver operating characteristic curve (AUROCs) were used to evaluate diagnostic accuracy of cpCD and global circumpapillary retinal nerve fiber layer (cpRNFL) thickness in the 2 groups after adjusting for confounders. MAIN OUTCOME MEASURES: Peripapillary capillary density and cpRNFL thickness measurements and their estimated loss. RESULTS: Participants of AD and ED with glaucoma were of similar age and glaucoma severity. After adjusting for age, disc area, and other confounders, significantly lower cpCD was found in ED eyes compared with AD eyes in mild glaucoma (mean, 42.2% [95% confidence interval (CI), 41.2%-43.2%] and 46.5% [95% CI, 44.8%-48.1%], respectively; adjusted difference, 4.4 [95% CI, 2.6-6.2]; P < 0.001) and moderate to advanced glaucoma (mean, 34.7% and 38.5%, respectively; adjusted difference, 4.8 [95% CI, 1.6-8.1]; P = 0.005). Although capillary density loss was greater in all sectors in ED compared with AD participants, a similar sectoral pattern of density loss was observed in both racial groups. Lower mean deviation and older age were associated with lower cpCD in both races in multivariate models. The adjusted AUROC for discriminating between healthy and glaucomatous eyes for cpCD was higher for ED (0.95) compared with AD (0.68) patients (P < 0.001). Sensitivity at 95% specificity in AD participants was lower than in ED participants for cpCD (0.32 [95% CI, 0.11-0.64] vs. 0.83 [95% CI, 0.69-0.93], respectively; P < 0.001). CONCLUSIONS: Although peripapillary capillary density parameters showed good diagnostic accuracy for detecting glaucoma in ED patients, their diagnostic accuracy was only modest in AD patients. Diagnostic performance of cpCD is race dependent, and clinicians should be aware that it has poorer performance in AD patients.

Impact of Pupil Dilation on Optical Coherence Tomography Angiography Retinal Microvasculature in Healthy Eyes.

PRéCIS:: Small but significant decreases in optical coherence tomography angiography (OCTA)-measured circumpapillary capillary density (cpCD) were observed in healthy eyes dilated with 2.5% phenylephrine/0.5% tropicamide. Although likely clinically insignificant, ophthalmologists should consider these changes when interpreting OCTA results from dilated eyes. PURPOSE: The purpose of this study was to investigate the effect of pupil dilation using 2.5% phenylephrine and 0.5% tropicamide on quantitative assessment of retinal microvasculature using OCTA. METHODS: OptoVue AngioVue high density (HD) and non-HD OCTA macula and optic nerve head (ONH) images were obtained at 15-minute intervals predilation and postdilation in 26 healthy participants (mean age: 40.0; 95% confidence interval=33.9, 46.1 y). Superficial macular vessel density (VD) was measured in the whole image VD and the parafoveal region VD. ONH capillary density was measured in the whole image capillary density and the cpCD region. Differences between predilation and postdilation densities were assessed using linear mixed effects models to account for within-patient correlation. RESULTS: Instillation of dilating drops resulted in a small but statistically significant reduction in non-HD ONH whole image capillary density of 0.6%, from a mean of 45.2% (95% confidence interval=41.9%, 48.4%) to 44.6% (41.4%, 47.8%) (P=0.046). A similar reduction in non-HD ONH cpCD of 0.8% also was observed, from a mean of 49.3% (45.3%, 53.3%) to 48.5% (44.5%, 52.4%) (P=0.025). No postdilation decreases in macular VD or HD ONH capillary density were observed. CONCLUSIONS: Pupil dilation using topical 2.5% phenylephrine and 0.5% tropicamide results in a small but statistically significant reduction in non-HD ONH whole image and cpCD in healthy eyes. The observed reduction likely is not clinically significant because the observed reduction was within the previously reported range of measurement variability. Further studies should consider investigating these effects in nonhealthy eyes with glaucoma and media opacities, as well as older individuals.

Capillary Density Measured by Optical Coherence Tomography Angiography in Glaucomatous Optic Disc Phenotypes.

PURPOSE: To compare optical coherence tomography angiography (OCTA)-measured capillary density of the optic disc among 4 glaucomatous optic disc phenotypes. DESIGN: Cross-sectional study. METHODS: Circumpapillary capillary density (cpCD) of 4 glaucomatous optic disc phenotypes in 193 eyes of 141 glaucoma patients and cpCD in 92 eyes of 55 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared. Areas under the receiver operating characteristic (AUROC) curves were used to evaluate diagnostic accuracy among groups after adjusting for confounders. RESULTS: Four glaucoma phenotypes were assessed: focal ischemic (n = 45), generalized cup enlargement (n = 60), myopic glaucoma (n = 38), and senile sclerotic (n = 50). Sex, mean ocular perfusion pressure, intraocular pressure, mean deviation, and the quality score did not differ among phenotypes. However, there were differences in age (P = .050), race (P = .039), axial length (P = .033), and retinal nerve fiber layer thickness (P < .001) among the groups. After adjusting for confounders, senile sclerotic discs had the lowest cpCD (37.1% [95% confidence interval, 35.3-38.8]), followed by focal ischemic (41.8% [40.0-43.6]), myopic glaucoma (42.1% [40-44.2]), and generalized cup enlargement (45.5% [44-47]) (P < .001) discs. The adjusted AUROC curves of cpCD for discriminating between healthy and glaucomatous eyes were highest in senile sclerotic eyes (0.928) and lowest in generalized cup enlargement eyes (0.704). CONCLUSIONS: OCTA-measured vessel density differs among optic disc phenotypes. Clinicians should be aware that the performance of OCTA for glaucoma diagnosis may be influenced by the optic disc phenotype.

Gradient-Boosting Classifiers Combining Vessel Density and Tissue Thickness Measurements for Classifying Early to Moderate Glaucoma.

PURPOSE: To compare gradient-boosting classifier (GBC) analysis of optical coherence tomography angiography (OCTA)-measured vessel density (VD) and OCT-measured tissue thickness to standard OCTA VD and OCT thickness parameters for classifying healthy eyes and eyes with early to moderate glaucoma. DESIGN: Comparison of diagnostic tools. METHODS: A total of 180 healthy eyes and 193 glaucomatous eyes with OCTA and OCT imaging of the macula and optic nerve head (ONH) were studied. Four GBCs were evaluated that combined 1) all macula VD and thickness measurements (Macula GBC), 2) all ONH VD and thickness measurements (ONH GBC), 3) all VD measurements from the macula and ONH (vessel density GBC), and 4) all thickness measurements from the macula and ONH (thickness GBC). ROC curve (AUROC) analyses compared the diagnostic accuracy of GBCs to that of standard instrument-provided parameters. A fifth GBC that combined all parameters (full GBC) also was investigated. RESULTS: GBCs had better diagnostic accuracy than standard OCTA and OCT parameters with AUROCs ranging from 0.90 to 0.93 and 0.64 to 0.91, respectively. The full GBC (AUROC = 0.93) performed significantly better than the ONH GBC (AUROC = 0.91; P = .036) and the vessel density GBC (AUROC = 0.90; P = .010). All other GBCs performed similarly. The mean relative influence of each parameter included in the full GBC identified a combination of macular thickness and ONH VD measurements as the greatest contributors. CONCLUSIONS: GBCs that combine OCTA and OCT macula and ONH measurements can improve diagnostic accuracy for glaucoma detection compared to most but not all instrument provided parameters.

Ganglion Cell Complex Thickness and Macular Vessel Density Loss in Primary Open-Angle Glaucoma.

PURPOSE: To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm2 GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated. MAIN OUTCOME MEASURES: The rates of GCC thinning and macular vessel density loss. RESULTS: Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 [-8.36, -5.88]%/year) was significantly faster than GCC thinning (-2.13 [-3.35, -0.90]%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease. CONCLUSIONS: Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

Diagnostic Ability of Optical Coherence Tomography Angiography Macula Vessel Density for the Diagnosis of Glaucoma Using Difference Scan Sizes.

PRéCIS:: There is diagnostic information in the outer region of optical coherence tomography angiography (OCT-A) macula scans not available in the inner region, and this information is especially useful in the early stages of glaucoma. PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of 3×3 and 6×6 mm macula OCT-A scans for classifying healthy, mild glaucoma, and moderate to severe glaucoma eyes. METHODS: Participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality 3×3 and 6×6 mm OCT-A images of the macula acquired on the same day were included in this cross-sectional study. The area under the receiver operating characteristic (AUC) curves were calculated to assess the diagnostic accuracy of vessel density (VD) of both scan sizes for differentiating between 3 diagnostic groups. RESULTS: Two hundred seventy-nine eyes (89 healthy, 127 with mild glaucoma, and 63 with moderate to severe glaucoma) from 190 subjects were included in this study. The VD of the outer area of the 6×6 mm scan size had higher diagnostic accuracy compared with the VD of the inner area of the 3×3 mm scan when differentiating between healthy and mild glaucoma (3×3 mm AUC=0.71 and 6×6 mm AUC=0.79, P=0.032). The VD of the outer area of the 6×6 mm scans had only similar diagnostic accuracy compared with the inner area of the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes (AUC=0.90 for 3×3 mm and 0.92 for 6×6 mm, P=0.279). The VD of the inner area of the 6×6 mm scan size had similar diagnostic accuracy to the corresponding area of the 3×3 mm scan in both diagnostic categories. CONCLUSION: The diagnostic accuracy of VD using the 6×6 mm macula OCT-A scan was better than the 3×3 mm scan when differentiating between healthy and mild glaucoma eyes, and similar to the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes.

Aqueous Angiographic Outflow Improvement after Trabecular Microbypass in Glaucoma Patients.

Purpose: To study changes in aqueous humor outflow (AHO) patterns after trabecular micro-bypass (TMB) in glaucoma patients using intraoperative sequential aqueous angiography. Design: Prospective comparative case series. Subjects: Fifteen subjects (14 with glaucoma and 1 normal). Methods: Sequential aqueous angiography (Spectralis HRA+OCT; Heidelberg Engineering) was performed on fourteen glaucoma patients undergoing routine TMB (iStent Inject; Glaukos Corporation) and cataract surgery and one normal patient undergoing cataract surgery alone. Indocyanine green (ICG) aqueous angiography established initial baseline nasal angiographic AHO patterns. Two TMB stents were placed in regions of baseline low or high angiographic AHO in each eye (n = 2 eyes with enough space to place two stents in both low angiographic regions; n = 8 eyes with two stents both placed in high angiographic regions; n = 4 eyes with enough space to place one stent in a low angiographic region and the other stent in a high angiographic region). Subsequent fluorescein aqueous angiography was utilized to query alterations to angiographic AHO patterns. Main Outcome Measure: Angiographic signal and patterns before and after TMB. Results: At baseline, all eyes showed segmental angiographic AHO patterns. Focused on the nasal hemisphere of each eye, for each stent TMB in initially low ICG angiographic signal regions showed transient or persistently improved fluorescein angiographic signal (11.2-fold; p = 0.014). TMB in initially high ICG signal regions led to faster development of fluorescein angiographic patterns (3.1-fold; p = 0.02). Conclusion: TMB resulted in different patterns of aqueous angiographic AHO improvement whose further understanding may advance basic knowledge of AHO and possibly enhance intraocular pressure reduction after glaucoma surgery in the future.

Association of Macular and Circumpapillary Microvasculature with Visual Field Sensitivity in Advanced Glaucoma.

PURPOSE: To evaluate the association between optical coherence tomography angiography (OCTA) macular and circumpapillary vessel density and visual field mean deviation (MD) in advanced primary open angle glaucoma. DESIGN: Cross-sectional study. METHODS: Macula (superficial layer) and optic nerve head (ONH) with capillary density (CD) and without vessel density (VD) automated removal of large vessels OCTA of 34 eyes (34 patients, MD < -10 dB) were investigated as macula whole image VD (wiVD), parafoveal VD (pfVD), ONH wiVD, wiCD, circumpapillary VD, and cpCD. Spectral domain OCT circumpapillary retinal nerve fiber layer, macular ganglion cell complex, and ganglion cell inner plexiform layer were also analyzed. RESULTS: Macular and ONH VD decreased significantly with worsening MD. Each 1-dB decrease in MD was associated with a reduction of 0.43% and 0.46% for macular wiVD and pfVD with R2 of 0.28 and 0.27, respectively (all P < .01). The association between MD and VD was strongest for measures of ONH with large vessels removed, wiCD, and cpCD, followed by wiVD and circumpapillary VD with R2 of 0.26, 0.22, 0.17, 0.14, and a VD reduction of 0.43%, 0.51%, 0.33%, and 0.40%, respectively (all P < .02). There was a reduction of 1.19 µm in Avanti parafoveal ganglion cell complex, 1.13 µm in Spectralis ganglion cell inner plexiform layer, and 1.01 µm in Spectralis circumpapillary retinal nerve fiber layer, with R2 of 0.19 (P = .006), 0.23 (P = .002), and 0.24 (P = .002), respectively. CONCLUSIONS: ONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma.

Measurement Floors and Dynamic Ranges of OCT and OCT Angiography in Glaucoma.

PURPOSE: To determine if OCT angiography (OCTA)-derived vessel density measurements can extend the available dynamic range for detecting glaucoma compared with spectral-domain (SD) OCT-derived thickness measurements. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 509 eyes from 38 healthy participants, 63 glaucoma suspects, and 193 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study. METHODS: Relative vessel density and tissue thickness measurement floors of perifoveal vessel density (pfVD), circumpapillary capillary density (cpCD), circumpapillary retinal nerve fiber (cpRNFL) thickness, ganglion cell complex (GCC) thickness, and visual field (VF) mean deviation (MD) were investigated and compared with a previously reported linear change point model (CPM) and locally weighted scatterplot smoothing curves. MAIN OUTCOME MEASURES: Estimated vessel density and tissue thickness measurement floors and corresponding dynamic ranges. RESULTS: Visual field MD ranged from -30.1 to 2.8 decibels (dB). No measurement floor was found for pfVD, which continued to decrease constantly until very advanced disease. A true floor (i.e., slope of approximately 0 after observed CPM change point) was detected for cpRNFL thickness only. The post-CPM estimated floors were 49.5±2.6 µm for cpRNFL thickness, 70.7±1.0 µm for GCC thickness, and 31.2±1.1% for cpCD. Perifoveal vessel density reached the post-CPM estimated floor later in the disease (VF MD, -25.8±3.8 dB) than cpCD (VF MD, -19.3±2.4 dB), cpRNFL thickness (VF MD, -17.5±3.3 dB), and GCC thickness (VF MD, -13.9±1.8 dB; P < 0.001). The number of available measurement steps from normal values to the CPM estimated floor was greatest for cpRNFL thickness (8.9), followed by GCC thickness (7.4), cpCD (4.5), and pfVD (3.8). CONCLUSIONS: In late-stage glaucoma, particularly when VF MD is worse than -14 dB, OCTA-measured pfVD is a promising tool for monitoring progression because it does not have a detectable measurement floor. However, the number of steps within the dynamic range of a parameter also needs to be considered. Although thickness parameters reached the floor earlier than OCTA-measured pfVD, there are more such steps with thickness than OCTA parameters.

Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

Importance: Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. Objectives: To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. Design, Setting, and Participants: This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Main Outcomes and Measures: Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. Results: The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] µm/y; difference, -0.43 [-0.76 to -0.09] µm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] µm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (ß2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (ß2, -0.05 [95% CI, -0.17 to 0.06], P = .36). Conclusions and Relevance: These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

Macula Vessel Density and Thickness in Early Primary Open-Angle Glaucoma.

PURPOSE: To characterize and compare the ganglion cell complex (GCC) thickness and macula vessel density in preperimetric and early primary open-angle glaucoma (POAG) eyes. DESIGN: Cross-sectional study. METHODS: Fifty-seven healthy, 68 preperimetric, and 162 early POAG eyes enrolled in the Diagnostic Innovations in Glaucoma Study. Optical coherence tomography angiography (OCT-A)-based superficial macula vessel density and OCT-based GCC thickness were evaluated simultaneously. Percent loss from normal of GCC thickness and macula vessel density was compared. Area under the receiver operating characteristic curve was used to describe the diagnostic utility. RESULTS: Both GCC thickness and vessel density were significantly lower in preperimetric and early POAG eyes compared to healthy eyes. Compared to the preperimetric POAG group, the early POAG group showed larger GCC thickness percent loss (whole image 4.72% vs 9.86%; all P < .01) but similar vessel density percent loss (whole image 4.97% vs 6.93%; all P > .05). In preperimetric POAG, GCC thickness and vessel density percent losses were similar (all P > .1). In contrast, in early POAG, GCC thickness percent loss was larger than that of vessel density (all P ≤ .001). To discriminate preperimetric or early glaucoma eyes from healthy eyes, GCC thickness and macula vessel density showed similar diagnostic accuracy (all P > .05). CONCLUSIONS: Both GCC thinning and macula vessel density dropout were detectable in preperimetric and early POAG eyes. GCC loss was greater than macula vessel density loss in early perimetric POAG. However, OCT-A and OCT measurements showed similar efficiency to detect early glaucoma.