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PurposeTo 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.DesignRandomized, single center, crossover clinical trial.MethodsEligible 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.ResultsOne 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).ConclusionsTopical 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.

PurposeTo compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).DesignCross-sectional study.ParticipantsEighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.MethodsGlobal and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.Main outcome measuresRetinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups.ResultsBoth global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P= 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P= 0.070]).ConclusionsAssociations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.

Face mask wearing has no significant effects on artifacts or vessel density measurements in optic nerve head (ONH) and macular optical coherence tomography-angiography (OCT-A) scans.The aim was to assess the difference in area of artifacts observed in optical OCT-A scans with and without face mask wear and to verify if mask wear interferes with OCT-A vessel density measurements.A total of 64 eyes of 10 healthy subjects, 4 ocular hypertensive, 8 glaucoma suspects, and 17 glaucoma patients were included.High-density ONH and macula OCT-A scans were obtained in patients with and without surgical masks. Seven different artifacts (motion, decentration, defocus, shadow, segmentation failure, blink, and Z-offset) were quantitatively evaluated by 2 trained graders. The changes in the area (% of scan area) of artifacts, without and with mask wearing, and differences of vessel density were evaluated.Trends of increasing motion artifact area for the ONH scans [4.23 (-0.52, 8.98) %, P=0.08] and defocus artifact area for the macular scans [1.06 (-0.14, 2.26) %, P=0.08] were found with face mask wear. However, there were no significant differences in the mean % area of any artifacts (P0.05 for all). Further, the estimated mean difference in vessel density in images acquired without and with masks was not significant for any type of artifact.Face mask wearing had no significant effect on area of artifacts or vessel density measurements. OCT-A vessel density measurements can be acquired reliably with face mask wear during the pandemic.

PURPOSE: To characterize the change of ganglion cell complex (GCC) thickness and macula vessel density in eyes diagnosed as being glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON). DESIGN: Prospective, longitudinal study. PARTICIPANTS: 83 eyes (24 healthy eyes, 30 OHT eyes, and 29 GON eyes) of 65 subjects who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years. METHODS: Optical coherence tomography angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3×3 mm(2) GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using linear mixed-effects model. MAIN OUTCOME MEASURES: Change rates of macula GCC thickness and superficial macula vessel density. RESULTS: Significant mean rates of both GCC thinning and macula vessel density loss were detectable in OHT and GON groups. 49.1% of the individual suspect eyes showed significant loss (P0.2). Higher mean intraocular pressure during follow-up was associated with a faster rate of 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: While the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes had 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.

Background/aimsTo investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects.MethodsOne hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model.ResultsAxial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2and POAG eyes 0.28 (0.27 to 0.30) mm2(p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all pConclusionsThe FD300, but not the FAZ area was correlated with 10° central visual field mean deviation and foveal threshold in healthy, glaucoma suspect and POAG eyes. In contrast, a smaller FAZ area was associated with lower IOP.

Non-contact measurement of facial temperature using infrared thermography has been used for mass screening of body temperature during a pandemic. We investigated the relative stability of temperature measurement in different facial regions of healthy individuals.Twenty healthy subjects underwent two experiments. In the first experiment, subjects washed their faces with a 20°C wet towel for 1 minute. Temperature changes compared to baseline in the forehead, cornea, inner canthus, and outer canthus were determined using an infrared camera for 10 minutes. In the second experiment, lubricating eye drops at 20°C were instilled over one eye. Temperature changes in the same regions of interest were monitored for 5 minutes.Baseline temperatures before face washing in the forehead and cornea, inner canthus, and outer canthus of the right eye were 33.4°C ± 0.8°C (mean ± SD), 33.3°C ± 0.8°C, 34.3°C ± 0.7°C, and 32.8°C ± 0.7°C, respectively. Reductions in temperature due to face washing were most significant for the forehead and least significant for the cornea. One minute after face washing, the corresponding changes were -2.8°C ± 0.6°C, -0.3°C ± 0.6°C, -0.6°C ± 0.7°C, and -0.9°C ± 0.7°C for the forehead, cornea, inner canthus, and outer canthus, respectively. After administering the eye drops, no significant temperature changes were observed.When facial temperature was exogenously cooled, the cornea had the most stable temperature readings.When using infrared thermography to screen facial temperature, the measurement of corneal temperature is probably a better representative if the stability of temperature readings is critical.

PurposeTo investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in patients with primary open-angle glaucoma with or without a history of disc hemorrhage (DH).DesignObservational cohort.MethodsIn this longitudinal study, 34 eyes with DH and 134 eyes without DH that had ≥1.5 years of follow-up and 3 optical coherence tomography and optical coherence tomography angiography follow-up scans were enrolled. A linear mixed-effects model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes.ResultsRates of whole image capillary density loss were faster in the DH group compared with the non-DH group (mean difference [95% confidence interval] -0.32% [-0.59% to -0.04%] per year; P=.027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P < .05). There was no statistically significant difference in the global rate of cpRNFL thinning between the 2 groups (P=.679). The mean rate of cpRNFL thinning was faster in the DH group compared with the non-DH group only in the inferotemporal sector (mean difference [95% confidence interval] -1.01 μm (-1.62 μm to -0.40 μm) per year; P=.001).ConclusionsMean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the 2 groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and patients with primary open-angle glaucoma.

PURPOSE: To determine the prevalence of different types of artifacts seen in optical coherence tomography angiography (OCTA) images of healthy and glaucoma eyes and to evaluate the characteristics associated with the increased likelihood of obtaining poor quality images. DESIGN: Retrospective study. PARTICIPANTS: A total of 649 eyes of 368 healthy, glaucoma suspect, and glaucoma patients. METHODS: Angiovue 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 using generalized linear mixed model. MAIN OUTCOME MEASURES: The prevalence of OCTA artifacts and the factors associated with increased likelihood of capturing poor quality OCTA images. RESULTS: 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 one (13.6%) or two or more artifacts (9.8%). Older age (P

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 μm at baseline and 0.04 ± 0.06 μm after 2 weeks of treatment (SD-OCT; p 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 μm

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. SUBJECTS AND CONTROLS: 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 one week. For both test protocols total deviation (TD) or pattern deviation (PD) plot CVFDs were defined by three contiguous points with probabilities of

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

AimsTo 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).Methods270 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.ResultsThinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=34.5% and R2=32.9%; respectively p0.1). 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%; p2=1.8%; p=0.028) and more strongly associated with more severe glaucoma VFMD (R2=29.6%; p2=15.5% pConclusionsAs 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.

Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for glaucoma remain a major unmet need. Recently, senescent cells have been observed in glaucomatous eyes, exposing a potential pathway for alternative glaucoma therapies. Prior studies demonstrated that targeting senescent RGCs for removal (i.e., a senolytic approach) protected healthy RGCs and preserved visual function in a mouse ocular hypertension model. However, the effects of senolytic drugs on vision in human patients are unknown. Here, we used existing clinical data to conduct a retrospective cohort study in 28 human glaucoma patients who had been exposed to senolytics. Senolytic exposure was not associated with decreased visual acuity, elevated intraocular pressure, or documentation of senolytic-related adverse ocular effects by treating ophthalmologists. Additionally, patients exposed to senolytics (n = 9) did not exhibit faster progression of glaucomatous visual field damage compared to matched glaucoma patients (n = 26) without senolytic exposure. These results suggest that senolytic drugs do not carry significant ocular toxicity and provide further support for additional evaluation of the potential neuroprotective effects of senolytics on glaucoma and other neurodegenerative diseases.

Purpose The coronavirus (COVID-19) pandemic has changed how outpatient care is delivered in ophthalmology clinics, particularly with glaucoma care. This case series highlights the need for awareness of fogging and improper face mask fit as causes of standard automated perimetry artifacts in patients with ocular hypertension and glaucoma. Clinical presentations Six patients with the diagnosis of ocular hypertension, glaucoma suspect, or glaucoma underwent standard automated perimetry (24-2 or 10-2 SITA, Humphrey Field Analyzer) while wearing ear-loop surgical face masks. Due to patient complaints of fogging during the testing, low test reliability, and unexpected results, the tests were repeated after taping securely the mask to the bridge of the nose. Clinical findings Fogging may reduce visual field (VF) test reliability and induce artifacts that mimic glaucomatous defects. VF test reliability can be improved and artifacts minimized following mask taping. In 1 case there was worsening of VF defects after mask taping. This suggests that fogging may also disguise true VF defects. Conclusions Fogging can result in unreliable VF testing with glaucoma-like artifacts. Secure taping of the face mask to the nose bridge may minimize this problem and reduce unnecessary additional testing and follow-up visits.

PURPOSE: To investigate central visual field (VF) defects among four phenotypes of glaucomatous optic discs. DESIGN: Cross-sectional study. METHODS: Optic disc phenotypes were determined in eyes with definite or suspected glaucoma that had a 24–2 VF with mean deviation (MD) better than −12 dB and a 10–2 VF. 10–2 VFs were classified as abnormal based on a cluster criterion. Additionally, the average of the total deviation values at each 10–2 test point was compared by optic disc phenotype. RESULTS: Four glaucomatous optic disc phenotypes were identified in 448 eyes of 309 patients: focal ischemic (FI)(n=121), generalized cup enlargement (GE)(n=109), myopic glaucoma (MY)(n=66), and senile sclerotic (SS)(n=152). Although VF 24–2 MD values were similar among optic disc phenotypes, GE eyes had higher VF 10–2 MD(p=0.004), as well as lower VF 24–2 pattern standard deviation(PSD)(p

SIGNIFICANCE Varying amounts of peripheral defocus reported in previous studies are likely due to whether peripheral defocus is measured while turning the eyes or the head. Contact lenses (CLs) lag when viewing objects in peripheral gaze, so future studies ought to measure peripheral defocus while turning the head to measure defocus through the peripheral add power. PURPOSE Soft multifocal CL peripheral defocus studies report varying results. To determine whether soft multifocal CL lag when turning the eyes could affect the measurement of peripheral defocus, we measured how much CLs move when looking in different gazes. METHODS The distance between limbus and CL edge was measured with a slit-lamp reticle magnifier. Centration was measured as the distance between CL edge and limbus at the superior, inferior, nasal, and temporal location of the CL while in primary gaze. Decentration of the CL equals the difference of the distance between the CL edge and limbus while looking centrally and 20 degrees in each direction. All measurements were performed while subjects wore habitual and Proclear Multifocal CL. RESULTS The average ± SD age of the 40 subjects was 27.8 ± 8.4 years, 65% were female, and SE refractive error was -4.43 ± 2.05 diopters. The soft multifocal CLs decentered 0.09 ± 0.03 mm temporal (P = .006). The soft multifocal CLs lagged 0.49 ± 0.28 mm while looking down (P < .001), 0.24 ± 0.36 mm while looking up (P = .008), 0.58 ± 0.20 mm while looking nasal (P < .001), and 0.35 ± 0.21 mm while looking temporal (P < .001). CONCLUSIONS Soft multifocal CLs center temporally in primary gaze, and they lag significantly while looking in every direction, but 0.50 mm or more when looking down or nasal, which could affect measurement of peripheral defocus when subjects turn their eyes instead of their head.

The purpose of this study was to investigate the effects of latanoprost, an ocular hypotensive prostaglandin analog, on scleral collagen fibers and laminar pores in myopic guinea pigs. Young guinea pigs underwent monocular form deprivation (FD; white plastic diffusers) from 14-days of age for 10-weeks. After the first week, FD eyes also received daily topical A) latanoprost (Lat, 0.005%, n = 5) or B) artificial tears (AT; n = 5). At the end of the treatment period, animals were sacrificed, eyes enucleated and optic nerve heads (ONH) excised to include a 4 mm diameter ring of surrounding sclera for scanning electron microscopy (SEM), and an additional 6 mm ring of sclera surrounding the ONH was excised for transmission electron microscopy (TEM). For SEM, ONH samples were first immersed in 0.2M NaOH for 30 h to isolate the collagenous structures. All samples were stained with osmium tetroxide, dried through an ethanol series and finally subjected to critical point drying before imaging. Image J was used to analyze the dimensions of laminar pores (SEM images) and scleral collagen fibers (TEM images). As previously reported in a related study, latanoprost was effective in inhibiting myopia progression in FD eyes of the guinea pigs. The scleral fibers of FD myopic eyes treated with AT were smaller and more variable in cross-sectional areas compared to untreated (fellow) eyes (mean areas: 0.0059 ± 0.0013 vs. 0.0085 ± 0.002 μm2; p

Author(s): El-Nimri, Nevin W; Wildsoet, Christine F | Abstract: Purpose:To determine whether latanoprost, a prostaglandin analog proven to be very effective in reducing intraocular pressure (IOP) in humans, can also slow myopia progression in the guinea pig form deprivation (FD) model. Methods:Two-week-old pigmented guinea pigs underwent monocular FD and daily topical latanoprost (0.005%, n = 10) or artificial tears (control, n = 10) starting 1 week after the initiation of FD, with all treatments continuing for a further 9 weeks. Tonometry, retinoscopy, and high-frequency A-scan ultrasonography were used to monitor IOP, refractive error, and ocular axial dimensions, respectively. Results:Latanoprost significantly reduced IOP and slowed myopia progression. Mean interocular IOP differences (±SEM) recorded at baseline and week 10 were -0.30 ± 0.51 and 1.80 ± 1.16 mm Hg (P = 0.525) for the control group and 0.07 ± 0.35 and -5.17 ± 0.96 mm Hg (P l 0.001) for the latanoprost group. Equivalent interocular differences for optical axial length at baseline and week 10 were 0.00 ± 0.015 and 0.29 ± 0.04 mm (P l 0.001; control) and 0.02 ± 0.02 and 0.06 ± 0.02 mm (P = 0.202; latanoprost), and for refractive error were +0.025 ± 0.36 and -8.2 ± 0.71 diopter (D) (P l 0.001; control), and -0.15 ± 0.35 and -2.25 ± 0.54 D (P = 0.03; latanoprost). Conclusions:In the FD guinea pig model, latanoprost significantly reduces the development of myopia. Although further investigations into underlying mechanisms are needed, the results open the exciting possibility of a new line of myopia control therapy.