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.

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.

Correlation between structure/function and optic disc microcirculation in myopic glaucoma, measured with laser speckle flowgraphy.

BACKGROUND: It is difficult to identify glaucoma in myopic eyes because the configuration of the optic disc varies; yet it is important clinically. Here, we used laser speckle flowgraphy (LSFG) to measure mean blur rate (MBR), representing optic disc microcirculation, and assessed its ability to identify glaucoma in eyes with myopic optic discs. METHODS: 129 eyes (normal disc: 21 eyes; myopic disc: 108 eyes) were enrolled. The eyes were classified as normal or mildly, moderately, or severely glaucomatous with standard automated perimetry (SAP). We determined the relationship between optic nerve head (ONH) MBR, measured with LSFG, mean deviation (MD), measured with SAP, and circumpapillary retinal nerve fiber layer thickness (cpRNFLT), measured with optical coherence tomography (OCT). RESULTS: ONH MBR and cpRNFLT decreased significantly with the severity of glaucoma. MBR was significantly correlated with cpRNFLT and MD (r =0.65 and r =0.63, respectively). A multiple regression analysis revealed that MBR and cpRNFLT were independent factors indicating glaucoma severity. A logistic regression analysis revealed that MBR and cpRNFLT were also independent factors indicating the presence of glaucoma. In a receiver operating characteristic (ROC) analysis, MBR and cpRNFLT could both differentiate between normal and glaucomatous eyes (MBR area under the ROC curve: 0.86, with a cut-off score of 24.0 AU). CONCLUSION: These results suggest that in addition to cpRNFLT, non-invasive and objective LSFG measurements of MBR may enable the identification of glaucoma and the classification of its severity in eyes with myopic optic discs.

Usefulness of laser speckle flowgraphy for the assessment of ocular blood flow in extracranial-intracranial bypass.

Laser speckle flowgraphy (LSFG) is a noninvasive technique that can measure relative blood flow velocity in the optic fundus. The authors present a case of symptomatic internal carotid artery occlusion treated with superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in which an improvement of ocular circulation was confirmed by LSFG. A 47-year-old man presented with a 1-month history of repeated left blurred vision and motor weakness of the right leg. Diffusion-weighted magnetic resonance imaging revealed a small infarction in the left frontal lobe. Carotid angiography revealed that the left internal carotid artery was occluded at the C4 portion. Single-photon emission computed tomography indicated that the cerebral blood flow in the left MCA territory was markedly impaired. Ophthalmologic examination revealed ischemic change of the left optic fundi, and LSFG revealed decreased blood flow around the left optic disc. Left STA-MCA bypass was successfully performed. Both ischemic ocular symptoms and the ischemic symptoms of the right leg were completely recovered after surgery. Postoperative ophthalmologic examination revealed improvement of both ischemic changes of the left optic fundi. Moreover, LSFG revealed improvement of the blood flow around the left optic disc. LSFG can be a promising clinical tool for the assessment of ocular circulation before and after bypass surgery for occlusive cerebrovascular disease.

[Analysis of retinal nerve fiber layer thickness in superior segmental optic hypoplasia (SSOH)].

PURPOSE: To evaluate the clinical characteristics of patients with superior segmental optic hypoplasia (SSOH) and quantitatively assess the structural characteristics using optical coherence tomography (OCT). METHODS: Forty-three eyes of 43 subjects with SSOH and 30 eyes of 30 normal subjects as controls (mean age; 40.2 +/- 14.1, 42.9 +/- 9.9 years, mean refraction; - 4.6 +/- 3.7 D, -3.6 +/- 2.7 D, mean intraocular pressure; 14.6 +/- 2.5 mmHg, 14.3 +/- 3.2 mmHg, Humphrey visual field mean deviation; -4.31 +/- 4.3 dB, 0.01 +/- 1.2 dB) were enrolled. Forty-three eyes of the 43 patients with SSOH were examined by OCT for the quantitative assessment of the RNFL thickness (RNFLT). For the comparison of RNFLT, total average thickness, four quadrants and clock hour-based (12 equal 30 degree sectors) RNFLT were analyzed using OCT. RESULTS: OCT showed that the eyes with SSOH had significantly thinner RNFL than the normal subjects in total average thickness (SSOH 81.2 mm vs. 105.0 mm, p < 0.0001). Except for the temporal guadrant (p = 0.31), RNFL was thinner in superior, nasal(both p < 0.0001) and inferior (p = 0.002) guadrant. A comparison between the SSOH group and the normal control group for the 12 clock-hour segments in the OCT demonstrated that the patients with SSOH had decreased peripapillary RNFL thickness; the difference was statistically significant, except for the 7, 8, 9 and 10 o'clock segments. The area under the receiver operator characteristic curve (AUC) was greatest for the RNFL thickness of the 12 o'clock segment (AUC = 0.93), followed by the 1 o'clock segment (AUC = 0.90), and the 2 o'clock segment (AUC- = 0.87), as measured by the OCT. CONCLUSIONS: More generalized thinning of the RNFL and decreasing total average thickness except for the RNFL from 7 o'clock to 10 o'clock were identified in the eyes with SSOH with a relatively superior entrance of the central retinal artery and thinning of the superior retinal nerve fiber layer. It was also demonstrated that segments 12, 1 and 2 o'clock of the SSOH were highly useful for differential diagnosis.

Short-term effects of acupuncture on open-angle glaucoma in retrobulbar circulation: additional therapy to standard medication.

Background. The relation between glaucoma and retrobulbar circulation in the prognosis has been indicated. Purpose. To investigate the effects of acupuncture on retrobulbar circulation in open-angle glaucoma (OAG) patients. Methods. Eleven OAG patients (20 eyes with OAG) who were treated by topical antiglaucoma medications for at least 3 months were enrolled. Acupuncture was performed once at acupoints BL2, M-HN9, ST2, ST36, SP6, KI3, LR3, GB20, BL18, and BL23 bilaterally. Retrobulbar circulation was measured with color Doppler imaging, and intraocular pressure (IOP) was also measured at rest and one hour after rest or before and after acupuncture. Results. The Δ value of the resistive index in the short posterior ciliary artery (P < .01) and the Δ value of IOP (P < .01) were decreased significantly by acupuncture compared with no acupuncture treatment. Conclusions. Acupuncture can improve the retrobulbar circulation and IOP, which may indicate the efficacy of acupuncture for OAG.

Difficulty in inserting 25- and 23-gauge trocar cannula during vitrectomy.

PURPOSE: To determine the incidence of difficulty in inserting a 25- and 23-gauge trocar cannula (DITC) during 25- or 23-gauge micro-incision vitrectomy surgery (MIVS). METHODS: Retrospective, consecutive, interventional case series performed by a single surgeon at a single centre. We defined a DITC as the condition where at least 1 trocar cannula could not be inserted into the vitreous at the beginning of MIVS. The incidence of DITC was calculated from 1,525 eyes, and the pre-operative demographics of the DITC cases were compared to those of the non-DITC cases. RESULTS: The incidence of DITC for all cases was 0.6% (9 of 1,525 eyes). Overall, there were 242 eyes with a retinal detachment (RD), and 8 of the 9 eyes with DITC had an RD with an incidence of 3.3% (8 of 242 RD eyes). Seven of these 8 eyes had a total RD, 4 also had a choroidal detachment, 4 eyes were also myopic (>-8.0 dpt, high myopia), and 6 of the 8 eyes were hypotonic (<8 mm Hg). The DITC cases had larger RDs (p<0.0001), a higher incidence of choroidal detachment (p<0.0001), higher myopia (p=0.0204) and hypotony (p=0.0003) than the non-DITC eyes with an RD. CONCLUSIONS: A large RD, a choroidal detachment, high myopia and hypotony are significant risk factors for DITC. We recommend that MIVS should be performed cautiously for eyes with these risk factors.

Successful surgical outcomes after 23-, 25- and 27-gauge vitrectomy without scleral encircling for giant retinal tear.

PURPOSE: Retinal detachment due to giant retinal tears (GRTs), tears larger than 90°, is rare and difficult to treat. Here, we show and compare surgical results of 23-, 25- and 27-gauge (G) micro-incision vitrectomy surgery (MIVS) for GRT. STUDY DESIGN: Retrospective and interventional case series. METHODS: Retrospective review of 41 eyes of 38 patients with GRT who underwent MIVS. Surgical outcomes after MIVS, including reattachment rates and postoperative complications, were compared between instrument gauges. All patients were followed for at least 6 months postoperatively. RESULTS: MIVS with 23G, 25G and 27G instruments was performed in 7, 19 and 15 eyes, respectively. Silicone oil (SO) was used in 34 of 41 eyes (83%) with a mean removal time of 43.8 days after first surgery. Best-corrected visual acuity (BCVA) was recovered or maintained in 39 eyes (95%). Reattachment was attained after initial surgery in 38 of 41 eyes (93%) (23G: 6/7 [86%]; 25G: 17/19 [89%]; 27G: 15/15 [100%]). Final reattachment was eventually achieved in all eyes (two eyes needed support from scleral encircling). Postoperative complications occurred in 16 eyes (39%) (23G: 3/7 [43%]; 25G: 8/19 [42%]; 27G: 5/15 [33%]), including macular pucker, cystoid macular edema, macular hole, subretinal perfluorocarbon liquid, retinal folds, vitreous hemorrhage and redetachment. There were no significant differences between the three groups in rate of high myopia, GRT size, operation time, phacovitrectomy rate, SO usage rate, initial reattachment rate, final reattachment rate, preoperative BCVA, final BCVA or rate of postoperative complications. CONCLUSION: Despite occasional postoperative complications, primary MIVS, regardless of gauge size, appears to be a safe and feasible option for GRT surgery.

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.

Quantitative analysis of the macula with optical coherence tomography angiography in normal Japanese subjects: The Taiwa Study.

This study evaluated age-related changes in the superficial and deep retinal capillary plexus (SCP and DCP, respectively) and in the foveal avascular zone (FAZ). SCP and DCP perfusion density (PD) were measured in optical coherence tomography angiography (OCTA) macular scans of 145 eyes of 145 healthy Japanese subjects, and findings were compared with SCP FAZ and clinical data. We found that age was negatively correlated with SCP and DCP PD (r = -0.17, P = 0.04 and r = -0.20, P = 0.02, respectively) and positively correlated with FAZ area (r = 0.18, P = 0.03). SCP and DCP PD were correlated with each other (r = 0.67, P < 0.001). FAZ area was negatively correlated with SCP PD, DCP PD and central macular thickness (CMT) (r = -0.18, P = 0.03; r = -0.25, P < 0.01; and r = -0.39, P < 0.001, respectively). FAZ was larger and CMT was lower (P = 0.01 and P < 0.001, respectively) in women than men. SCP and DCP PD were positively correlated with estimated glomerular filtration rate (r = 0.17, P = 0.03 and r = 0.24, P < 0.01, respectively). Multiple regression analysis confirmed that age independently affected DCP PD and FAZ (P = 0.02 and P < 0.01, respectively) and that CMT independently affected FAZ area (P < 0.001). Thus, normal subjects showed age-related decreases in macular PD and renal function. FAZ and CMT were related, suggesting that age-related changes in macular thickness also affect capillary vasculature.

Color visual acuity in preperimetric glaucoma and open-angle glaucoma.

PURPOSE: To investigate the clinical significance of color visual acuity (CVA) in preperimetric glaucoma (PPG) and open-angle glaucoma (OAG). METHODS: A total of 123 eyes of 73 subjects (22 normal eyes, 14 PPG eyes, and 87 OAG eyes; mean age: 44.9 ± 10.1 years, age range: 21-64 years) were enrolled. CVA was tested for red, green-yellow, blue-green and blue-purple with a newly developed test. RESULTS: There was no statistical difference in clinical background factors, including age, sex, intraocular pressure, or spherical equivalent between the three groups. Red VA and blue-green VA were significantly worse in the OAG eyes than in the normal eyes (P = 0.008 and P = 0.015, respectively), although green-yellow VA and blue-purple VA were not significantly worse. Furthermore, red VA and blue-green VA were significantly correlated with MD in a group of eyes with either PPG or OAG (r = -0.23, P = 0.023; r = -0.25, P = 0.012, respectively), but green-yellow VA and blue-purple VA were not. CONCLUSION: Red VA and blue-green VA were detectably worse in eyes with OAG, in close association with the degree of functional loss. This suggests that measuring CVA with the new color test described here may be a promising supplement to existing methods of detecting glaucoma and evaluating its severity.

Surgical results of internal limiting membrane flap inversion and internal limiting membrane peeling for macular hole.

PURPOSE: The internal limiting membrane (ILM) is a normal part of the retina, and the outcomes of ILM removal have not been fully investigated. ILM flap inversion is a recently developed technique that increases the success rate of macular hole (MH) surgery. Thus, we compared the anatomical closure rate and visual outcome in patients undergoing microincision vitrectomy surgery (MIVS) with ILM flap inversion or conventional ILM peeling for the treatment of MH. METHODS: The medical records of 90 eyes with MH were reviewed retrospectively. The patients were classified into two groups based on MIVS procedure (group 1: ILM flap inversion, 46 eyes; group 2: ILM peeling, 44 eyes). RESULTS: Preoperative characteristics were similar in the two groups, and there were no significant differences in 1 month- or 6 month-postoperative VA between the groups (P = 0.25 and P = 0.42, respectively). However, the surgical success rate was significantly higher in group 1 than group 2 (P = 0.04; 46/46: 100% and 41/44: 93%, respectively). Multiple regression analysis revealed that axial length and MH diameter were independent factors predicting 6-month postoperative BCVA in group 2 (P = 0.001 and P = 0.03, respectively), and that MH diameter was an independent factor predicting 6-month postoperative VA in group 1 (P = 0.03). Logistic regression analysis revealed that axial length (OR = 2.11; P = 0.02; area under the curve: 0.94; cut off score: 28.4 mm) was an independent factor indicating surgical failure in group 2. CONCLUSION: Our results suggest that MIVS with ILM flap inversion might be best suited to treat MH, particularly in patients with high myopia.

Levels of Anti-Retinal Antibodies in Retinal Detachment and Proliferative Vitreoretinopathy.

PURPOSE: The purpose of the study is to investigate the correlation between intraocular anti-retinal antibodies and clinical measurements in patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS: Aqueous humor and vitreous samples were collected from patients with RRD, PVR, and from control subjects with macular hole. The levels of total protein (TP), IgG, and anti-retinal antibodies were determined with a bicinchoninic acid assay, enzyme-linked immunosorbent assay, and dot blot, respectively. Correlations between these measurements were assessed using Pearson's correlation test. Analysis of variance followed by a post-hoc test or the Student t-test was used to compare differences between groups. RESULTS: The levels of anti-retinal antibodies and IgG were correlated with each other (P < 0.010). The IgG concentration was higher in patients with PVR than in controls in both the aqueous humor (P < 0.001) and the vitreous (P < 0.001), but not in patients with RRD. Conversely, TP levels and anti-retinal antibodies in both ocular fluids from RRD and PVR patients did not significantly differ from the controls. In a subgroup analysis, vitreal anti-retinal antibody levels were correlated with average macular thickness in the re-attached macula following surgery for macula-off RRD/PVR (P = 0.012). Furthermore, patients with post-operative cystoid macular edema had a higher level of vitreal anti-retinal antibodies than those without (P = 0.009). CONCLUSIONS: Intravitreal anti-retinal antibodies were increased in the eyes with maculopathy after surgical intervention for RRD/PVR.