Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

The Relationship Between Artificial Intelligence-Assisted OCT Angiography-Derived Foveal Avascular Zone Parameters and Visual-Field Defect Progression in Eyes with Open-Angle Glaucoma.

Purpose: To investigate clinical factors associated with foveal avascular zone (FAZ) parameters obtained using OCT angiography (OCTA) with assistance from a previously developed artificial intelligence (AI) platform in eyes with open-angle glaucoma (OAG). Design: Retrospective longitudinal. Participants: This study followed up 885 eyes of 558 patients with OAG for ≥ 2 years; all eyes underwent ≥ 5 Humphrey visual-field (VF) tests and had 3.0 × 3.0 mm macular OCTA scans available. Methods: Average total deviation (TD) in the superior, superocentral, inferocentral, and inferior sectors of the Humphrey 24-2 program was calculated. We collected 3.0 × 3.0 mm macular OCTA images from each patient and used a previously developed AI platform with these images to obtain FAZ parameters, including FAZ area, FAZ circularity index (CI), and FAZ perimeter. Multivariable linear mixed-effects models were used to analyze the relationship between FAZ parameters, TD or TD slope in each quadrant, and systemic factors, adjusting for potential confounding factors, including axial length. Main Outcome Measures: Ophthalmic and systemic variables, FAZ parameters, and TD or TD slope in each quadrant. Results: The multivariable model showed that FAZ parameters were correlated with both TD and TD slope in the inferocentral quadrant (ß = -0.244 - 0.168, P < 0.001). Both upper-half and lower-half FAZ parameters were better associated with TD-inferocentral and TD-inferocentral slope than TD-superocentral or TD-superocentral slope in terms of ß size and statistical significance, indicating that there was no evident vertical anatomical correspondence between TD in the central quadrant and FAZ parameters. Foveal avascular zone area enlargement was associated with female gender (ß = 0.242, P = 0.003). Loss of FAZ circularity was associated with both aging and comorbid sleep apnea syndrome (SAS) (yes: 1, no: 0) (ß = -0.188, P < 0.001; ß = -0.261, P = 0.031, respectively). Foveal avascular zone perimeter elongation was associated with aging and female gender (ß = 0.084, P = 0.040; ß = 0.168, P = 0.042, respectively). Conclusions: Artificial intelligence-assisted OCTA-measured FAZ enlargement and irregular shape might be good markers of ocular hypoperfusion and associated inferocentral VF defect progression in eyes with OAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Relationship between nailfold capillaroscopy parameters and the severity of diabetic retinopathy.

PURPOSE: To determine whether non-invasive measurements of the nailfold capillaries (NCs) are associated with the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: Eighty-three eyes of 83 patients with type 2 diabetes were enrolled. Sixty-three age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: non-DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). We used nailfold capillaroscopy to measure NC parameters, including number, length, width, and turbidity. RESULTS: Four NC parameters in the diabetic patients were significantly lower than in the controls (all P < 0.001). There was a statistically significant decrease in the NC parameters along with the increasing severity of DR (number: P = 0.02; all others: P < 0.001). Logistic regression analysis revealed that combining the systemic characteristics of age, sex, systolic blood pressure, estimated glomerular filtration rate, hemoglobin A1c level, and history of hypertension and dyslipidemia could indicate the presence of DR and PDR (the area under the receiver operating characteristic curve [AUC] = 0.81, P = 0.006; AUC = 0.87, P = 0.001, respectively). Furthermore, the discriminative power of DR was significantly improved (P = 0.03) by adding NC length to the systemic findings (AUC = 0.89, P < 0.001). CONCLUSION: NC measurement is a simple and non-invasive way to assess the risk of DR and its severity.

Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab.

PURPOSE: To investigate baseline characteristics associated with the incidence of intraocular inflammation (IOI) after the intravitreal injection of brolucizumab (IVBr) for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This retrospective study included 66 eyes of 62 consecutive patients with nAMD who received IVBr (18 eyes were treatment naïve and 48 eyes had switched from other anti-vascular endothelial growth factor [VEGF] therapy). Baseline clinical characteristics were compared in non-IOI and IOI groups. RESULTS: Although a dry macula was achieved at a high rate even 6 months after IVBr, IOI occurred in 8 of 66 eyes (12.1%; all had switched therapy) during the study period. Baseline characteristics including age, sex, nAMD type, lens status, visual acuity, central macular thickness, and a history of diabetes did not differ between the groups. The number of previous anti-VEGF injections before IVBr was greater in the IOI group (P = 0.004), and the ratio of patients with a laser flare-cell photometry (LFCP) value over 15 photon count per millisecond (pc/ms) was higher in the IOI group (P = 0.017). Multivariate logistic regression analysis showed that a greater number of previous anti-VEGF injections (odds ratio [OR]: 1.12, P = 0.006; area under the curve: 0.82, cut-off score: 14.0) and an LFCP value over 15 pc/ms (OR: 81.6, P = 0.031) were significantly associated with the incidence of IOI after IVBr. CONCLUSION: A number of previous anti-VEGF injections greater than 14 and an LFCP value more than 15 pc/ms might be useful predictors of the incidence of IOI after IVBr in eyes with nAMD.

Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma.

Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

Sex differences in the association between systemic oxidative stress status and optic nerve head blood flow in normal-tension glaucoma.

PURPOSE: To investigate the association of systemic oxidative stress markers and optic nerve head (ONH) blood flow in normal-tension glaucoma (NTG) patients, as well as sex differences in this association. METHODS: This was a cross-sectional study of 235 eyes with NTG of 134 patients (56 male, 78 female; mean age, 60.9±14.1 years). Laser speckle flowgraphy (LSFG) was used to measure ONH blood flow (mean blur rate in the tissue area of the ONH; MBR-T) and LSFG pulse-waveform parameters, including flow acceleration index in the tissue area of the ONH (FAI-T). Oxidative stress markers, diacron-reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) were measured with a free radical elective evaluator. Spearman's rank correlation test and a multivariate linear mixed-effect model were used to investigate factors associated with ONH blood flow. RESULTS: MBR-T was significantly correlated with age (rs = -0.28, p < 0.001), mean arterial pressure (rs = -0.20, p = 0.002), intraocular pressure (rs = 0.24, p < 0.001), peripapillary retinal nerve fiber layer thickness (rs = 0.62, p < 0.001), and disc area (rs = -0.26, p < 0.001), but not with serum d-ROM level. Separate analyses of the subjects divided by sex showed that BAP was positively correlated to MBR-T (rs = 0.21, p = 0.036) and FAI-T (rs = 0.36, p < 0.001) only in male subjects. Similarly, BAP was significantly associated with MBR-T (ß = 0.25, p = 0.026) and FAI-T (ß = 0.37, p < 0.001) in male subjects in a multivariate linear mixed-effect model. CONCLUSION: A lower serum antioxidant level, as indicated by BAP, was associated with reduced ONH blood flow only in male NTG patients. Our findings suggest that there are sex differences in the involvement of oxidative stress in the pathogenesis of reduced ocular blood flow in NTG.

CHOP deletion and anti-neuroinflammation treatment with hesperidin synergistically attenuate NMDA retinal injury in mice.

Glaucoma is a leading cause of blindness worldwide and is characterized by degeneration associated with the death of retinal ganglion cells (RGCs). It is believed that glaucoma is a group of heterogeneous diseases with multifactorial pathomechanisms. Here, we investigate whether anti-inflammation treatment with an ER stress blockade can selectively promote neuroprotection against NMDA injury in the RGCs. Retinal excitotoxicity was induced with an intravitreal NMDA injection. Microglial activation and neuroinflammation were evaluated with Iba1 immunostaining and cytokine gene expression. A stable HT22 cell line transfected with an NF-kB reporter was used to assess NF-kB activity after hesperidin treatment. CHOP-deficient mice were used as a model of ER stress blockade. Retinal cell death was evaluated with a TUNEL assay. As results, in the NMDA injury group, Iba1-positive microglia increased 6 h after NMDA injection. Also at 6 h, pro-inflammatory cytokines and chemokine increased, including TNFα, IL-1b, IL-6 and MCP-1. In addition, the MCP-1 promoter-driven EGFP signal, which we previously identified as a stress signal in injured RGCs, also increased; hesperidin treatment suppressed this inflammatory response and reduced stressed RGCs. In CHOP-deficient mice that received an NMDA injection, the gene expression of pro-inflammatory cytokines, chemokines, markers of active microglia, and inflammatory regulators was greater than in WT mice. In WT mice, hesperidin treatment partially prevented retinal cell death after NMDA injury; this neuroprotective effect was enhanced in CHOP-deficient mice. These findings demonstrate that ER stress blockade is not enough by itself to prevent RGC loss due to neuroinflammation in the retina, but it has a synergistic neuroprotective effect after NMDA injury when combined with an anti-inflammatory treatment based on hesperidin.

Polypoidal choroidal vasculopathy in a case of retinitis pigmentosa, successfully treated with intravitreal aflibercept.

PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a subtype of age-related macular degeneration that is seen frequently in Asians. Nevertheless, it is rare for this condition to be combined with retinitis pigmentosa (RP). The purpose of this paper is to present findings from this rare combination in a Japanese patient, and to describe its successful treatment with intravitreal aflibercept (IVA). OBSERVATIONS: The patient was a 71-year-old Japanese woman with RP (diagnosed at the age of 30) and PCV. She noticed a decrease in vision in her right eye 6 months previously. Decimal best-corrected visual acuity (BCVA) was 0.05 in her right eye. Optical coherence tomography and indocyanine green angiography (IA) revealed serous retinal detachment (SRD) and PCV in her right eye. The SRD was initially resolved after 3 monthly treatments with IVA, but recurrences began 5 months later, requiring four more treatments with IVA, performed about every 4 months within the next 12 months, for successful resolution. There were no recurrences of PCV in 7 more months of follow-up, as confirmed with IA at the final appointment. Final decimal BCVA in the right eye improved to 0.15. Furthermore, macular retinal sensitivity, measured with microperimetry, increased after the treatment, and RP-related visual field narrowing, determined by Goldmann perimetry, did not progress throughout follow up of 26 months. CONCLUSION: More than 2 years of follow up showed that IVA may be effective for treating PCV, even in RP patients, and can increase central visual function without causing progression of RP-related visual field narrowing.

Ocular microcirculation changes, measured with laser speckle flowgraphy and optical coherence tomography angiography, in branch retinal vein occlusion with macular edema treated by ranibizumab.

PURPOSE: This study searched for early predictive vascular biomarkers for visual outcomes in eyes with macular edema caused by branch retinal vein occlusion (BRVOME). METHODS: Twenty-four eyes of 24 subjects with BRVOME were treated with the intravitreal injection of ranibizumab (IVR) for at least 6 months. We measured mean blur rate (MBR) in the optic nerve head (ONH) and vessel density (VD) in the macula with laser speckle flowgraphy and optical coherence tomography angiography, respectively. RESULTS: Six-month post-IVR best-corrected visual acuity (BCVA) was correlated positively with age, pre-IVR BCVA, 1-month post-IVR BCVA, 3-month post-IVR BCVA and pre-IVR systolic blood pressure (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.02, respectively) and negatively with pre-IVR overall MBR, 1-month post-IVR overall MBR, 6-month post-IVR overall MBR, 3-month post-IVR deep retinal capillary plexus (DCP) VD and 6-month post-IVR DCP VD (P = 0.03, P = 0.03, P = 0.02, P = 0.01 and P = 0.005, respectively). Furthermore, a multiple regression analysis showed that pre-IVR overall MBR (ß = - 0.67, P = 0.009) was among independent prognostic factors predicting 6-month post-IVR BCVA. Six-month post-IVR DCP VD was also correlated with overall MBR at all time points. CONCLUSION: ONH blood flow may be a pre-IVR biomarker of both visual outcomes and post-IVR deep macular microcirculation in eyes with BRVOME.

RETINAL SENSITIVITY AND VESSEL DENSITY AFTER MACULAR HOLE SURGERY WITH THE SUPERIOR INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE.

PURPOSE: To evaluate retinal vessel density and retinal sensitivity (RS) after macular hole surgery with the superior inverted internal limiting membrane flap technique. METHODS: Retrospective, observational case series. Twenty-one patients with idiopathic macular hole underwent 27-gauge vitrectomy with the superior inverted internal limiting membrane flap technique and triamcinolone acetonide. Measurements included RS, which was measured with microperimetry, as well as retinal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), which was measured with optical coherence tomography angiography. All parameters were evaluated in the superior and inferior sectors of the macula preoperatively and 1, 3, and 6 months postoperatively. RESULTS: Six months postoperatively, retinal thickness in the inferior sector was unchanged, but retinal thickness in the superior sector decreased significantly (P < 0.01). SCP vessel density in both sectors was unchanged at all postoperative time points. DCP vessel density in both sectors increased very significantly at 3 months (P < 0.01) and returned to baseline at 6 months. RS in the inferior sector increased by 47% 3 months postoperatively and by 61% 6 months postoperatively (P < 0.05 and P < 0.001, respectively), but RS in the superior sector increased only at 6 months postoperatively and only by 22% (P < 0.05). CONCLUSION: Lower recovery of RS in the superior sector suggests that internal limiting membrane peeling might affect the postoperative visual function.

Carotid artery intima-media thickness, HDL cholesterol levels, and gender associated with poor visual acuity in patients with branch retinal artery occlusion.

PURPOSE: To investigate factors associated with poor visual acuity (VA) in branch retinal artery occlusion (BRAO). METHODS: This was a retrospective cross-sectional study of 72 eyes with BRAO of 72 patients. For statistical comparison, we divided the patients into worse-VA (decimal VA < 0.5) and better-VA (decimal VA > = 0.5) groups. We examined the association of clinical findings, including blood biochemical test data and carotid artery ultrasound parameters, with poor VA. RESULTS: Median age, hematocrit, hemoglobin and high-density lipoprotein (HDL) differed significantly between the groups (P = 0.018, P < 0.01, P < 0.01, and P = 0.025). There was a tendency towards higher median IMT-Bmax in the worse-VA group (worse-VA vs. better-VA: 2.70 mm vs. 1.60 mm, P = 0.152). Spearman's rank correlation test revealed that logMAR VA was significantly correlated to IMT-Bmax (rs = 0.31, P < 0.01) and IMT-Cmax (rs = 0.24, P = 0.035). Furthermore, logMAR VA was significantly correlated to HDL level (rs = -0.33, P < 0.01). Multivariate logistic regression analysis revealed that IMT-Bmax (odds ratio [OR] = 2.70, P = 0.049), HDL level (OR = 0.91, P = 0.032), and female gender (OR = 15.63, P = 0.032) were independently associated with worse VA in BRAO. CONCLUSIONS: We found that increased IMT-Bmax, decreased HDL, and female sex were associated with poor VA in BRAO patients. Our findings might suggest novel risk factors for visual dysfunction in BRAO and may provide new insights into the pathomechanisms underlying BRAO.

Progression in Open-Angle Glaucoma with Myopic Disc and Blood Flow in the Optic Nerve Head and Peripapillary Chorioretinal Atrophy Zone.

PURPOSE: To investigate the effect of blood flow in the temporal optic nerve head (ONH) and peripapillary chorioretinal atrophy (PPA) zone on central visual field (VF) defects and progression in eyes with open-angle glaucoma (OAG) and myopic disc. DESIGN: Retrospective longitudinal medical chart review. PARTICIPANTS: This study comprised 366 eyes of 245 OAG patients with myopic disc, followed for at least 2 years with at least 5 reliable VF tests. OCT and laser speckle flowgraphy (LSFG) were performed at baseline. METHODS: We analyzed the relationship between temporal ONH-tissue mean blur rate (MBR), temporal PPA-tissue MBR, total deviation (TD)-central, and TD-central slope with a linear mixed-effects model. Additionally, we investigated background factors influencing temporal PPA-tissue MBR. Main outcome measures were basic ophthalmic and systemic variables, baseline ONH-tissue MBR, baseline PPA-tissue MBR, baseline TD, and TD slope. RESULTS: Lower temporal ONH-tissue MBR was associated with both worse TD-central and faster TD-central slope (ß = 0.30, P < 0.001; ß = 0.18, P = 0.001, respectively). However, lower temporal PPA-tissue MBR was only associated with faster TD-central slope (ß = 0.15, P = 0.005). Lower ONH-tissue MBR and lower PPA-tissue MBR were significant independent contributors to worse TD-central slope, after adjusting for potential confounding factors (ß = 0.12 to 0.15, P < 0.05). The multivariate analysis showed that lower pulse rate, larger temporal PPA area, and lower circumpapillary retinal nerve fiber layer thickness were associated with lower PPA-tissue MBR (P < 0.05). CONCLUSIONS: Measurement of systemic variables and LSFG analysis might help clinicians to predict central VF defect severity and progression in OAG eyes with myopic disc.

Vascular resistance of carotid and vertebral arteries is associated with retinal microcirculation measured by laser speckle flowgraphy in patients with type 2 diabetes mellitus.

AIMS: Evaluation of the retinal microcirculation is key to understanding retinal vasculopathies, such as diabetic retinopathy. Laser speckle flowgraphy (LSFG) has recently enabled us to directly evaluate the vascular resistance in both retinal vessels and capillaries, non-invasively. We therefore assessed whether retinal vessel blood flow and/or the capillary microcirculation are associated with blood flow in the cervical arteries in diabetic patients without severe retinopathy. METHODS: We enrolled 110 type 2 diabetes patients, with no or mild non-proliferative diabetic retinopathy, in this prospective cross-sectional study. We measured the resistivity indices (RIs) of the retinal vessel and capillaries by LSFG and those of cervical arteries by Doppler ultrasonography, followed by analyzing associations. RESULTS: The RIs of not only the carotid but also vertebral arteries were associated with those of retinal vessel blood flow and the retinal capillary microcirculation. Multiple regression analyses revealed these associations to be independent of other explanatory variables including age and diabetes duration. CONCLUSIONS: We obtained novel and direct evidence demonstrating a close association between the retinal microcirculation and cervical artery hemodynamics in diabetic patients. These findings suggest shared mechanisms to underlie micro- and macro-angiopathies. Thus, high vascular resistance of cervical arteries may be a risk of developing retinopathy.

Association of retinal vessel density with retinal sensitivity in surgery for idiopathic epiretinal membrane.

PURPOSE: The success of surgical treatment for idiopathic epiretinal membrane (ERM) is measured by postoperative best-corrected visual acuity (BCVA), metamorphopsia, and foveal retinal sensitivity (RS).This study searched for predictive biomarkers of surgical success by determining the association between foveal RS and various aspects of vessel density (VD) in the fovea of patients with ERM. METHODS: The study examined 25 eyes of 25 patients with ERM who underwent 27-gauge microincision vitrectomy surgery (MIVS). RS was measured with microperimetry (MP-3; NIDEK) at four central points in the fovea with an interpoint distance of 2°. VD was measured with SD-OCT (RS 3000; NIDEK) within the 1-mm2 square defined by the 4 RS points at various depths, including the superficial and deep retinal capillary plexus (SCP and DCP, respectively). RESULTS: Though VD did not change throughout the follow-up period, BCVA and RS significantly improved 1 and 3 months after surgery, respectively (both P < 0.0017). Postoperative RS at 6 months was positively correlated with postoperative DCP VD at 1, 3, and 6 months (r = 0.62, P = 0.001; r = 0.40, P = 0.049; r = 0.53, P = 0.007, respectively), but not with SCP VD at any time point. Multiple regression analysis confirmed that postoperative RS at 6 months was associated with postoperative DCP VD at 1 month (P = 0.03). CONCLUSION: Higher postoperative DCP VD at 1 month contributed to better postoperative foveal RS at 6 months. Early postoperative VD in the fovea might be a useful predictive biomarker of late postoperative RS in the fovea in ERM patients.

The optic nerve head vasoreactive response to systemic hyperoxia and visual field defect progression in open-angle glaucoma, a pilot study.

PURPOSE: To investigate the effect of optic nerve head (ONH) tissue vasoreactivity on glaucoma visual field defect progression. METHODS: This prospective, longitudinal study comprised 28 eyes of 16 patients with open-angle glaucoma. Baseline data were obtained from oxygen inhalation testing, including laser speckle flowgraphy measurements of tissue-area mean blur rate (MT), which represents ONH tissue blood flow, and the mean percentage change in MT (MT-change). Follow-up data were collected for at least 2 years, including at least 5 reliable visual field tests. The average total deviation (TD) was calculated in each sector of the Garway-Heath map; in this study, superior, central and inferior TD corresponded to inferior, temporal and superior MT or MT-change, respectively. MT and MT-change in three sectors per eye were included as explanatory variables in a multivariable linear mixed-effects model, with TD slope set as the response variable. RESULTS: At baseline, lower MT and higher diastolic blood pressure were associated with lower MT-change (p < 0.05). Additionally, MT-change significantly contributed to TD slope in the corresponding sectors (ß = 0.41, p = 0.01). CONCLUSIONS: Weaker ONH tissue vasoreactivity to systemic hyperoxia, assessed with laser speckle flowgraphy, was associated with lower baseline ONH tissue blood flow, higher diastolic blood pressure and rapid visual field defect progression. Laser speckle flowgraphy variables during oxygen provocation testing may represent potentially useful predictive biomarkers of glaucoma progression.

Sectoral Differences in the Association of Optic Nerve Head Blood Flow and Glaucomatous Visual Field Defect Severity and Progression.

Purpose: To investigate sectoral differences in the relationship between optic nerve head tissue blood flow, anatomically corresponding visual field defect severity, and future progression. Methods: This retrospective longitudinal medical chart review comprised 508 eyes of 319 open-angle glaucoma patients (mean deviation: -9.2 ± 7.0 dB), followed for an average of 4.7 ± 1.1 years; an average 11.7 ± 3.7 visual field tests were performed. Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 program. The optic nerve head was divided to obtain inferior, temporal, and superior tissue-area mean blur rate (MT), derived from laser speckle flowgraphy. At baseline, the correlation between MT and TD was compared in anatomically corresponding sectors. We performed a multivariate analysis to determine the contribution of baseline MT to corresponding TD slope and to determine background factors influencing superior to temporal MT. We used a linear-mixed effect model for the statistical analysis. Results: At baseline, the highest ß coefficients were found between MT-superior and TD-inferior, MT-temporal and TD-central, and between MT-inferior and TD-superior, in that order (ß = 0.38, ß = 0.27, ß = 0.26, respectively). MT-superior and MT-temporal independently contributed to corresponding TD slope (P < 0.05). Male sex, high body mass index, and the prevalence of sleep apnea syndrome were contributing factors to lower superior to temporal MT (P < 0.05). Conclusions: Review of medical history, measurements of systemic variables, and laser speckle flowgraphy parameters might help clinicians to predict visual field defect severity and progression.

The Relationship between Carotid Intima-Media Thickness and Ocular Circulation in Type-2 Diabetes.

PURPOSE: To compare clinical findings, including ocular blood flow and intima-media thickness (IMT) of the carotid artery, in mild nonproliferative diabetic retinopathy (NPDR) and no diabetic retinopathy (NDR) patients, and to determine risk factors contributing to mild NPDR. METHODS: In 129 subjects (129 eyes) with type-2 diabetes patients and mild NPDR or NDR, standard statistical techniques were used to determine associations between clinical findings, including diabetes duration, blood levels of creatinine and hemoglobin A1c (HbA1c), central macular thickness (CMT; measured with optical coherence tomography), mean blur rate (MBR; measured with laser speckle flowgraphy), and ultrasound-measured carotid IMT. RESULTS: Diabetes duration, IMT, and CMT were significantly higher in the mild NPDR patients than the NDR patients (P=0.004, P=0.004, and P=0.003, respectively), while conversely, MBR in the overall optic nerve head (MBR-A) was lower in the mild NPDR patients. Furthermore, a logistic regression analysis showed that diabetes duration (OR, 1.11; P=0.006), diastolic blood pressure (OR, 0.93; P=0.025), heart rate (OR, 1.07; P=0.004), IMT (OR, 8.65; P=0.005), and CMT (OR, 1.03; P=0.007) were independent contributing factors to mild NPDR. Spearman's rank correlation test also showed that IMT was negatively correlated with MBR-A (P=0.011). CONCLUSIONS: Increased IMT showed a close association with ocular ischemia in patients with type-2 diabetes and contributed to the presence of mild NPDR. These findings suggest that IMT may be an early biomarker of mild NPDR.

The Impact of Intraocular Pressure Elevation on Optic Nerve Head and Choroidal Blood Flow.

Purpose: To use laser speckle flowgraphy (LSFG) to assess blood flow (BF) in the optic nerve head (ONH) tissue and choroid during elevated intraocular pressure (IOP). Methods: This prospective study included 20 eyes of 20 healthy volunteers. The testing protocol had a baseline phase, two elevated IOP phases (+10 and +20 mm Hg), and a recovery phase. IOP was elevated by pushing against the eyelid with a novel tubular device attached to the LSFG apparatus. Measurement parameters in each phase included: LSFG-derived mean blur rate (MBR) and flow acceleration index (FAI); systemic parameters, and IOP. The % change against baseline was calculated for each phase. The protocol was repeated five times to calculate the coefficient of variation (CV) for % change MBR and to determine the effect of mydriasis on % change MBR. We compared % change MBR and FAI and evaluated the relationship between % change ocular perfusion pressure (OPP) and MBR in the choroid and ONH tissue. Results: The % change MBR was highly reproducible (CV: 6.1-8.7%) and not affected by mydriasis (P = 0.57-0.96). The % change MBR and FAI were higher in the ONH tissue than choroid during IOP elevation (P = 0.04). The % change OPP and MBR showed positive linear correlations and two-segmental linear correlations in the choroid and ONH tissue, respectively (P < 0.01). Conclusion: Hemodynamics during IOP elevation differ in the choroid and ONH tissue. LSFG enables highly reproducible assessment of the dynamic autoregulation of ocular BF in the ONH tissue.