Comparison of the Circumpapillary Structure-Function and Vasculature-Function Relationships at Different Glaucoma Stages Using Longitudinal Data.

Purpose: This study investigated the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) data using circumpapillary retinal nerve fiber layer thickness (cpRNFLT) measurements from optical coherence tomography (OCT), circumpapillary vessel density (cpVD) from OCT angiography (OCTA), and the corresponding visual field mean sensitivities at different glaucoma stages. Methods: A total of 107 eyes from 107 glaucoma patients with progressive visual field (VF) changes followed up for an average of 3.33 ± 1.39 years were enrolled, including early-to-moderate (51 eyes) and advanced (56 eyes) stages. The rates of longitudinal change in the VF mean deviation (MD), cpRNFLT, and cpVD were evaluated using linear mixed-effects models and compared between different glaucoma stages. Longitudinal global and regional S-F and V-F relationships were assessed by repeated measures correlation analysis by glaucoma stage. Results: No significant differences were found in the rates of VF MD and cpVD changes (P > 0.05) between the two glaucoma stage groups. CpRNFLT decreased more rapidly in the early-to-moderate stage group (P < 0.001) in which significant longitudinal global and regional correlations were found in both S-F and V-F relationships (all P < 0.05), except for the nasal sector. Significant global and regional correlations were only found in V-F relationship in advanced stage cases (all P < 0.05). Conclusions: Significant longitudinal V-F relationships exist globally and regionally regardless of glaucoma stage but no longitudinal S-F relationship is present in advanced glaucoma. Longitudinal follow-up of cpVD parameters may be useful for monitoring glaucomatous VF progression at all disease stages.

Progressive Macular Vessel Density Loss and Visual Field Progression in Open-angle Glaucoma Eyes with Central Visual Field Damage.

PURPOSE: To investigate the association between the longitudinal changes in both macular vessel density (mVD) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and visual field (VF) progression (including central VF progression) in open-angle glaucoma (OAG) patients with central visual field (CVF) damage at different glaucoma stages. DESIGN: Retrospective longitudinal study. PARTICIPANTS: This study enrolled 223 OAG eyes with CVF loss at baseline classified as early-to-moderate (133 eyes) or advanced (90 eyes) stage based on the VF mean deviation (MD) (-10 dB). METHODS: Serial mVDs at parafoveal and perifoveal sectors and mGCIPLT measurements were obtained using OCT angiography and OCT during a mean follow-up of 3.5 years. Visual field progression was determined using both the event- and trend-based analyses during follow-up. MAIN OUTCOME MEASURES: Linear mixed-effects models were used to compare the rates of change in each parameter between VF progressors and nonprogressors. Logistic regression analyses were performed to determine the risk factors for VF progression. RESULTS: In early-to-moderate stage, progressors showed significantly faster rates of change in the mGCIPLT (-1.02 vs. -0.47 µm/year), parafoveal (-1.12 vs. -0.40%/year), and perifoveal mVDs (-0.83 vs. -0.44%/year) than nonprogressors (all P < 0.05). In advanced stage cases, only the rates of change in mVDs (parafoveal: -1.47 vs. -0.44%/year; perifoveal: -1.04 vs. -0.27%/year; all P < 0.05) showed significant differences between the groups. By multivariable logistic regression analyses, the faster rate of mVD loss was a predictor of VF progression regardless of glaucoma stage, while the rate of mGCIPLT loss was significantly associated with VF progression only in early-to-moderate stage cases. CONCLUSIONS: Progressive mVD loss is significantly associated with VF progression (including central VF progression) in the OAG eyes with CVF loss regardless of the glaucoma stage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Utility of targeted mean total deviation trend analysis for detecting progressive visual field changes in early-to-moderate stage glaucoma.

OBJECTIVES: To evaluate the clinical utility of trend-based analysis of the targeted mean total deviation (TMTD) by comparing its rates of visual field (VF) change and sensitivities of detecting VF progression with those of the mean total deviation (mTD) in the global and hemifield VF area in early to-moderate glaucoma patients. METHODS: A single eye from 139 open-angle glaucoma patients with hemifield VF defects and a minimum two year follow-up were retrospectively evaluated. The TMTD was estimated by averaging the total deviation (TD) values after excluding VF points that had a threshold sensitivity of <0 dB in three baseline tests, and the mTD by averaging the entire VF TD values. The study patients were classified as VF progressors vs. non-progressors using both event- and trend-based analysis. The rates of change and ratios of progression detection were compared between TMTD and mTD. RESULTS: This study included 49 VF progressors and 90 non-progressors. Slopes for the global and VF-affected hemifield TMTD were significantly faster than those for the mTD in each subgroup and in the entire cohort (P < 0.001). Trend-based TMTD analysis detected VF progression in greater proportion than either trend-based mTD or event-based analysis (38.1% vs. 30.2% vs. 27.3%, respectively: VF affected hemifields). CONCLUSIONS: The rates of change in the TMTD are significantly faster than those for the mTD globally and in the VF-affected hemifields. Trend-based TMTD analysis shows greater sensitivity for detecting VF progression than trend-based mTD or event-based analysis in early-to-moderate glaucoma patients with hemifield VF loss.

Foveal avascular zone vessel density is associated with visual field progression in early-stage glaucoma eyes with central visual field damage.

We investigated the relationship between foveal avascular zone (FAZ)-related parameters, assessed by optical coherence tomography angiography (OCT-A), and visual field (VF) progression in early-stage open-angle glaucoma (OAG) eyes with central visual field (CVF) defects. Early-stage glaucoma eyes [VF mean deviation (MD) ≥ - 6 dB] with CVF defects were included. The rates of longitudinal change in FAZ-related parameters and structural parameters were evaluated and compared between VF progressors and non-progressors, using linear mixed effects models. Cox proportional hazards model and linear regression models were used to identify factors associated with VF progression, the VF MD reduction rate and the change rate of mean total deviation in central 12 VF points (MTD10). A total of 131 eyes were included and VF progression was detected in 32 eyes (24.4%) during 3.45 years of follow-up. The rates of reduction in vessel density in the 300 µm width annular region surrounding the FAZ (FD300) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) were significantly faster in progressors than in non-progressors. The faster VF MD or MTD10 reduction rates were associated with faster rates of FD300 loss and mGCIPLT reduction. The FD300 reduction rate is significantly associated with VF progression in early-stage OAG eyes with CVF defects. FD300 may be an adjunctive biomarker of VF progression in glaucomatous eyes with CVF defects.

Association of superficial macular vessel density with visual field progression in open-angle glaucoma with central visual field damage.

Identifying the clinical relevance of superficial versus deep layer macular vessel density (mVD) in glaucoma is important for monitoring glaucoma patients. Our current retrospective longitudinal study investigated the association of superficial and deep layer mVD parameters with glaucomatous visual field (VF) progression in mild to moderate open-angle glaucoma (OAG) eyes with central visual field (CVF) damage. Serial optical coherence tomography (OCT) angiography-derived mVD measurements were obtained in 182 mild to moderate OAG eyes (mean deviation ≥ -10 decibels). Forty-eight eyes (26.4%) showed VF progression during a mean follow-up of 3.5 years. The parafoveal and perifoveal mVDs of both superficial and deep layers showed significantly faster reduction rates in the VF progressors than in the non-progressors according to linear mixed effects models (P < 0.05). Cox and linear regression analyses showed that greater reduction rates of both the superficial layer parafoveal and perifoveal mVDs, but not their deep layer counterparts, were significant predictors of VF progression and faster VF loss (P < 0.05). In conclusion, faster rates of change in superficial but not deep layer mVD parameters are significantly associated with subsequent VF progression and faster VF deterioration in mild to moderate OAG eyes with CVF damage.

Associations Between the Macular Microvasculatures and Subclinical Atherosclerosis in Patients With Type 2 Diabetes: An Optical Coherence Tomography Angiography Study.

Objective: To investigate the associations between the macular microvasculature assessed by optical coherence tomography angiography (OCTA) and subclinical atherosclerosis in patients with type 2 diabetes. Methods: We included patients with type 2 diabetes who received comprehensive medical and ophthalmic evaluations, such as carotid ultrasonography and OCTA at a hospital-based diabetic clinic in a consecutive manner. Among them, 254 eyes with neither diabetic macular edema (DME) nor history of ophthalmic treatment from 254 patients were included. The presence of increased carotid intima-media thickness (IMT) (>1.0 mm) or carotid plaque was defined as subclinical atherosclerosis. OCTA characteristics focused on foveal avascular zone (FAZ) related parameters and parafoveal vessel density (VD) were compared in terms of subclinical atherosclerosis, and risk factors for subclinical atherosclerosis were identified using a multivariate logistic regression analysis. Results: Subclinical atherosclerosis was observed in 148 patients (58.3%). The subclinical atherosclerosis group were older (p < 0.001), had a greater portion of patients who were men (p = 0.001) and who had hypertension (p = 0.042), had longer diabetes duration (p = 0.014), and lower VD around FAZ (p = 0.010), and parafoveal VD (all p < 0.05). In the multivariate logistic regression analysis, older age (p ≤ 0.001), male sex (p ≤ 0.001), lower VD around FAZ (p = 0.043), lower parafoveal VD of both superficial capillary plexus (SCP) (p = 0.011), and deep capillary plexus (DCP) (p = 0.046) were significant factors for subclinical atherosclerosis. Conclusion: The decrease in VD around FAZ, and the VD loss in parafoveal area of both SCP and DCP were significantly associated with subclinical atherosclerosis in patients with type 2 diabetes, suggesting that common pathogenic mechanisms might predispose to diabetic micro- and macrovascular complications.

Effect of preoperative eyedrops on cytokine concentrations in aqueous humor of patients undergoing femtosecond laser-assisted cataract surgery.

PURPOSE: To compare the anti-inflammatory activity of preoperatively applied eyedrops, as determined by cytokine concentrations in aqueous humor collected during surgery in patients undergoing femtosecond laser-assisted cataract surgery. METHODS: A total of 120 patients undergoing femtosecond laser-assisted cataract surgery were randomly assigned to four groups of 30 patients each. Groups were administered 0.1% fluorometholone eyedrops, 0.45% ketorolac tromethamine eyedrops, both 0.1% fluorometholone and 0.45% ketorolac tromethamine eyedrops, or no eyedrops. Eyedrops were instilled 1 h, 20 min, and just before surgery. After anterior capsulotomy and nuclear fragmentation using a femtosecond laser, 0.1 cc aqueous humor was obtained using a needle and syringe. Cytokine and prostaglandin E2 (PGE2) concentrations were quantitatively determined. RESULTS: The 120 patients included 59 men and 61 women, of mean age 65.02 years. The mean interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations after treatment did not differ significantly in the four groups. The average interleukin-8 (IL-8) concentrations were significantly lower in the fluorometholone (4.80 pg/mL), ketorolac tromethamine (4.84 pg/mL), and fluorometholone + ketorolac tromethamine (4.68 pg/mL) groups than in the control group (6.83 pg/mL). Furthermore, the average PGE2 concentrations were significantly lower in the ketorolac tromethamine (270.04 pg/mL) and fluorometholone + ketorolac tromethamine (239.00 pg/mL) groups, but not in the fluorometholone (393.16 pg/mL) group, than in the control group (472.36 pg/mL). CONCLUSION: Preoperative fluorometholone instillation reduced IL-8, and ketorolac tromethamine instillation reduced IL-8 and PGE2, in aqueous humor of patients undergoing femtosecond laser surgery, with the combination of both eyedrops being more effective than either alone. TRIAL REGISTRATION: KCT0005717.

Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma with IgG4-related ophthalmic disease.

PURPOSE: To analyse the incidence and characteristics of ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD), and to compare with IgG4-negative OAML. METHODS: We enrolled 130 patients with pathology-confirmed OAML at a single tertiary medical centre. Patients were divided into IgG4-positive and IgG4-negative groups based on the pathologic criteria for IgG4-ROD. The data were reviewed and compared between the groups. RESULTS: IgG4-positive OAML was identified in 5.4% (7/130) of OAML and 13.5% (7/52) of non-conjunctival OAML. IgG4-positive group had a higher incidence of involvement of the lacrimal gland (7/7 vs. 18/123, p = .001), extraocular muscles (3/7 vs. 10/123, p = .022) and infraorbital nerve (2/7 vs. 0/123, p < .001), and had a lower incidence of involvement of the conjunctiva (0/7 vs. 84/123; p < .001) than IgG4-negative group. IgG4-positive group had higher T and N categories of the American Joint Committee on Cancer classification (T1:T2:T3:T4 ratio of 0:6:0:1 vs. 78:32:8:5, p < .001; and ≥N1 ratio of 2/7 vs. 7/123, p = .021). There were no differences in the response rate to initial treatment (5/6 vs. 39/41, p = .343) or the relapse rate (1/6 vs. 5/41, p = 1.000) between the groups. CONCLUSION: IgG4-positive OAML showed clinical features similar to IgG4-ROD, such as predominant disease involvement of the lacrimal gland, extraocular muscles, infraorbital nerve and lymph nodes, but not the conjunctiva. However, treatment outcomes were favourable with or without background IgG4-ROD. Physicians should be aware that IgG4-ROD might undergo a malignant transformation and that thorough treatment and surveillance of IgG4-ROD are important.

Changes in Peripapillary and Macular Vessel Densities and Their Relationship with Visual Field Progression after Trabeculectomy.

The aim of this study was to determine the factors associated with visual field (VF) deterioration after trabeculectomy, including the peripapillary vessel density (pVD) and macular vessel density (mVD) changes assessed by optical coherence tomography angiography (OCT-A). Primary open-angle glaucoma patients with more than two years of follow-up after trabeculectomy were included. pVD was calculated in a region defined as a 750 µm-wide elliptical annulus extending from the optic disc boundary. mVD was calculated in the parafoveal (1-3 mm) and perifoveal (3-6 mm) regions. VF deterioration was defined as the rate of mean deviation (MD) worse than -1.5 dB/year. The change rates of pVD and mVD were compared between the deteriorated VF and non-deteriorated VF groups. The factors associated with the rate of MD were determined by linear regression analyses. VF deterioration was noted in 14 (21.5%) of the 65 eyes that underwent trabeculectomy. The pVD (-2.26 ± 2.67 vs. -0.02 ± 1.74%/year, p ≤ 0.001) reduction rate was significantly greater in the deteriorated VF group than in the non-deteriorated VF group, while that of parafoveal (p = 0.267) and perifoveal (p = 0.350) VD did not show a significant difference. The linear regression analysis showed that the postoperative MD reduction rate was significantly associated with the rate of pVD reduction (p = 0.016), while other clinical parameters and preoperative vascular parameters did not show any association. Eyes with greater loss of peripapillary retinal circulation after trabeculectomy tended to exhibit VF deterioration. The assessment of peripapillary vascular status can be an adjunctive strategy to predict visual function after trabeculectomy.