Greater Central Subfield Thickness Research Articles

Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVERESTII Study.

The EVERESTII study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6years after initiation of the EVERESTII study. This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVERESTII study. The long-term outcomes were assessed during a recall visit at about 6years from commencement of EVERESTII. The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year6 (- 179.9 vs - 74.2µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year6 include BCVA (year2), CST (year2), presence of SRF/IRF at year2, and number of anti-VEGF treatments (years2-6). Factors associated with presence of SRF/IRF at year6 include combination arm (OR 0.45, p = 0.033), BCVA (year2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year2) (OR 2.59, p = 0.042). At 6years following the EVERESTII study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. ClinicalTrials.gov identifier, NCT01846273.

Central subfield thickness predicts visual acuity outcomes in plaque-irradiated eyes with choroidal melanoma.

To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. Single-center retrospective study. Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 μm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.

OCT Grading System of Macular Infarction Predicts Vision in Participants With Central Retinal or Hemiretinal Vein Occlusion: A Secondary Analysis of SCORE2

To determine whether macular infarction measured as hyper-reflectivity of the middle and inner retinal layers predicts long-term visual acuity outcomes in participants with central retinal vein occlusion (CRVO) or hemi-retinal vein occlusion (HRVO). Clinical cohort study using post hoc secondary analysis of phase 3 clinical trial data. This post hoc secondary analysis of the phase 3 Study of COmparative Treatments for REtinal Vein Occlusions 2 (SCORE2) clinical trial included 310 of the 362 participants with macular edema secondary to CRVO/HRVO who were randomized to injections of aflibercept or bevacizumab. Month 01 (M01) optical coherence tomography (OCT) images were analyzed using the following grading scheme: no infarction (grade 0), only middle retinal infarction (grade 1), diffuse middle and patchy inner retinal infarction (grade 2), and diffuse middle and inner retinal infarction (grade 3). Visual acuity letter score (VALS), central subfield thickness (CST), and number of anti-vascular endothelial growth factor (anti-VEGF) injections were correlated with the infarction severity grade at month 01. More severe macular infarction, with both middle and inner retinal layer hyper-reflectivity (ie, grades 2 and 3), was associated with worse M00 VALS and was predictive of VALS at M01 to M60 (P < .001). More severe infarction was associated with greater CST at presentation; however, after the first anti-VEGF injection, CST decreased and was similar across all grades at all time points (P > .05) with similar number of injections. Participants with more severe macular infarction at M01, as graded with OCT, exhibited worse visual outcomes despite significantly improved macular edema from month 6 to 5 years. This suggests that macular infarction may drive visual acuity after retinal fluid is treated with anti-VEGF.

Visual, Anatomic Outcomes, and Natural History of Retinal Nerve Fiber Layer Schisis in Patients Undergoing Epiretinal Membrane Surgery

To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERMs) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice. Retrospective case-control study. Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013 to2021. Patients were grouped by the presence or absence of sRNFL before surgery. Preoperative and postoperative data were collected regarding visual acuity (VA), changes in central subfield thickness (CST) over time, and presence of cystoid macular edema. Frequency of sRNFL in patients undergoing idiopathic ERM surgery. Overall, 48 (53.9%) of 89 patients presented with sRNFL. Schisis of the retinal nerve fiber layer patients presented with significantly decreased VA compared with those without (58.63 ± 12.48 vs. 67.68 ± 7.84 ETDRS letters, P < 0.001, respectively). At the final follow-up after ERM removal, there was no significant difference in final VA in patients with sRNFL compared with those without (71.16 ± 2.93 vs. 74.11 ± 2.76, P=0.467). At presentation, patients with sRNFL had greater CST than those without (454 ± 10.01 vs. 436 ± 0.23, P= 0.23). This difference persisted at the 90-day follow-up after ERM removal (402 ± 8.08 vs. 375 ± 10.19 μm, P= 0.043). The resolution of sRNFL was reported at postoperative week 1 in 30 (96.7%) of 31 cases. Schisis of the retinal nerve fiber layer is a microstructural feature in > 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively. Proprietary or commercial disclosure may be found after the references.

Characteristics of major and macular branch retinal vein occlusion

We compared the aqueous profiles, baseline characteristics, and clinical outcomes of 54 eyes with macular edema secondary to major branch retinal vein occlusion (BRVO) and macular BRVO. We also identified the characteristics of poor responders to anti-vascular endothelial growth factor (VEGF) injections. Aqueous inflammatory cytokine and VEGF concentrations were significantly higher in major BRVO. In optical coherence tomography, major BRVO had a higher proportion with subretinal fluid, disorganization of retinal inner layers, and ellipsoid zone disruption. Comparing the clinical outcomes, major BRVO required more intravitreal anti-VEGF injections and had a poorer visual prognosis in the first 12 months. A significantly higher proportion of patients with major BRVO required additional treatments after 6 months compared to macular BRVO. Patients who responded poorly to anti-VEGF had higher aqueous VEGF levels and central subfield thickness (CST) at baseline. In conclusion, major BRVO patients required more and longer treatments, and had worse visual prognoses. BRVO that responds poorly to anti-VEGF had greater CST and higher aqueous VEGF levels at baseline.

Aqueous humor analyses of diabetic macular edema patients with subretinal fluid

We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF.

En face image-based classification of diabetic macular edema using swept source optical coherence tomography

This retrospective study was performed to classify diabetic macular edema (DME) based on the localization and area of the fluid and to investigate the relationship of the classification with visual acuity (VA). The fluid was visualized using en face optical coherence tomography (OCT) images constructed using swept-source OCT. A total of 128 eyes with DME were included. The retina was segmented into: Segment 1, mainly comprising the inner nuclear layer and outer plexiform layer, including Henle’s fiber layer; and Segment 2, mainly comprising the outer nuclear layer. DME was classified as: foveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 24), parafoveal cystoid space at Segment 1 and no fluid at Segment 2 (n = 25), parafoveal cystoid space at Segment 1 and diffuse fluid at Segment 2 (n = 16), diffuse fluid at both segments (n = 37), and diffuse fluid at both segments with subretinal fluid (n = 26). Eyes with diffuse fluid at Segment 2 showed significantly poorer VA, higher ellipsoid zone disruption rates, and greater central subfield thickness than did those without fluid at Segment 2 (P < 0.001 for all). These results indicate the importance of the localization and area of the fluid for VA in DME.

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders.

Purpose:A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting.Methods:A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up).Results:Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 μm from 409.4 ± 85.8 μm to 290.0 ± 64.5 μm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039).Conclusion:Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.

Central Macular Thickness in a Healthy Mexican Population Using Huvitz Optical Coherence Tomography.

ObjectiveTo determine normal macular thickness values in a healthy Mexican population and its variation by age and gender using Huvitz spectral-domain optical coherence tomography (HOCT-1F).MethodsThis cross-sectional study included 211 consecutive eyes from clinically normal subjects (66 men, 145 women) between October 2018 and December 2018, with best-corrected visual acuities better than 20/30. One eye was selected for the macular scan using the Huvitz OCT (Huvitz OCT-1F, HOCT-1F, Huvitz Co., Ltd., Republic of Korea) with an automated segmentation algorithm. Three vertical and horizontal scans, centered on the fovea with an area of 9 mm, and a color 45° fundus photograph were obtained using Huvitz OCT-1F. Macular measurements were presented as means with standard deviations values for each of the nine regions defined by the Early Treatment Diabetic Retinopathy Study (ETDRS).ResultsThe mean age was 34.3±11.9 years. Using the ETDRS map, the mean central subfield thickness (CST) was 227.4±18.9 µm. Male gender was associated with greater CST (P<0.001) compared to females. There was no association between mean macular CST (r2=0.011; P=0.11) and age. Macular thickness was thicker in the inner ring than in the outer ring, and there were no significant differences in mean CST among age groups (P=0.70).ConclusionNormal macular thickness values using the Huvitz OCT in a Mexican healthy population aged from 18–70 years were thinner in the foveal macular region than values reported in other populations. Female patients had a thinner CST, and age was not correlated with macular thickness.

Sex Differences in Presentation, Treatment Patterns, and Clinical Outcomes in Central Retinal Vein Occlusion.

To evaluate the impact of sex differences on the presenting features, treatment patterns, and clinical outcomes in patients with central retinal vein occlusions (CRVO). This retrospective, longitudinal cohort study included 476 patients diagnosed with CRVO over a 7-year period. Charts were reviewed and clinical data were abstracted. The average age at CRVO onset was lower in males (63.8 years vs. 66.1 years; P = .048). More males (104/224, 54%) had an ischemic CRVO compared to females (113/252, 45%) at 12 months (P = .05). Males with CRVO had a greater central subfield thickness at the baseline (546.7 ± 306.8 μm vs. 438.4 ± 252.9 μm; P = .003) and final visits (343 ± 179.5 μm vs. 304.6 ± 176.2 μm; P = .005). Foveal avascular zone enlargement was more likely in males (39/102, 38% vs. 29/116, 25%; P = .04). Sex differences exist in presenting features of patients with CRVO. Further inquiry may help provide individualized recommendations for management of CRVO. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:279-285.].

Defining Cystoid Macular Degeneration in Diabetic Macular Edema: An OCT-Based Single-center Study

Objectives:To describe cystoid macular degeneration (CMD), which has no clear definition in diabetic macular edema (DME), and examine its features in optical coherence tomography (OCT) and fundus fluorescein angiography (FFA).Materials and Methods:This study was conducted using OCT images of patients who were followed in Gazi University between November 2011 and March 2015. A total of 259 eyes (187 patients) found to have cystic changes on OCT were included. Macular ischemia, peripheral ischemia, and type of edema were identified on FFA. Vitreomacular interface abnormalities, foveal contour integrity, internal reflectivity of the cysts, and outer retinal layer defects were analyzed from OCT images. The horizontal and vertical diameters of the largest cyst within 1000 μm of the foveal center were measured for the definition of CMD. Cut-offs for these values were determined by receiver operating characteristic curve analysis. Cystoid macular edema (CME) and CMD groups were created and their characteristics were analyzed.Results:The horizontal and vertical diameters of the largest cyst were moderately positively correlated with visual acuity (rs=0.349, r=0.419, respectively). Eyes with horizontal diameter of the largest cyst ≥450 μm were classified as CMD; in this group, sensitivity in the prediction of visual acuity ≤20/60 was 58%. Eyes with horizontal diameter of the largest cyst <450 μm were classified as CME; in this group, specificity in the prediction of visual acuity >20/60 was 73%. For the threshold of 300 μm determined for vertical diameter of the largest cyst, sensitivity was 62% and specificity was 69%. The CME and CMD groups were formed according to these cut-off values. Compared to the CME group, the CMD group had greater central subfield thickness and higher prevalence of outer retinal damage, severe disruption of foveal contour, macular ischemia, and diffuse/mixed type edema.Conclusion:In eyes with DME, CMD can be defined as the largest cyst within 1000 μm of the foveal center having a horizontal diameter of ≥450 μm and vertical diameter ≥300 μm, especially if associated with macular ischemia, outer retinal damage, loss of foveal contour, and diffuse/mixed type edema.

The Relationship Between Macular Cyst Formation and Ischemia in Diabetic Macular Edema

Objectives:To evaluate the relationship between cyst characteristics and macular and peripheral ischemia in diabetic macular edema (DME).Materials and Methods:We retrospectively reviewed eyes with DME and included those with clinically significant macular edema as defined by ETDRS (Early Treatment Diabetic Retinopathy Study) and cystoid spaces in optical coherence tomography scans in this study. Central subfield thickness (CSFT), horizontal and vertical diameters of the largest cyst, cyst area, and the remaining retinal thickness outside the cyst were determined. The presence and number of hyperreflective foci in the cyst wall and the internal reflectivity of the cyst were analyzed. Outer retinal damage was graded. Fluorescein angiography was used to determine the areas of macular and peripheral ischemia, which were graded as mild or severe. Correlations between macular and peripheral ischemia and cyst-related measurements and structural changes in the retina were evaluated.Results:This retrospective study included 250 eyes of 186 patients with DME. Mean CSFT was significantly greater in eyes with macular ischemia (510.4±144.7 μm) compared to eyes without macular ischemia (452.1±114.6 μm) (p=0.001). Horizontal and vertical diameter of the largest cyst increased with the presence and severity of macular ischemia (p=0.045 and p=0.016, respectively). Remaining retinal thickness increased with the presence and severity of peripheral ischemia (p=0.009). There was a statistically significant relationship between the number of the hyperreflective foci in the cyst wall and internal reflectivity of the cyst (p=0.007). Patients with greater CSFT had a 1.04-times higher odds of having macular ischemia and 0.25-times higher odds of having outer retinal damage.Conclusion:The likelihood of macular ischemia increases with larger cyst diameter, CSFT, and extent of outer retinal damage. Thickness of the noncystic area is increased in the presence of peripheral ischemia.

Baseline Ocular Characteristics of Patients Undergoing Initiation of Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema.

Patients with diabetic macular edema (DME) have variable anatomic and visual responses to anti-vascular endothelial growth (VEGF) treatments based on their presenting visual acuity (VA). The aim of study is to report the baseline ocular and imaging characteristics of patients presenting with DME who were treatment-naïve and who initiated anti-VEGF in routine clinical practice. Single-center, cross-sectional study of 638 patients. Subjects were divided into two VA groups: Early Treatment Diabetic Retinopathy Study (ETDRS) less than 70 and ETDRS greater than 70 and ocular variables were compared between groups. Average central subfield thickness (CST) was 363.5 μm, cube volume was 11.7 mm3, and cube average thickness (CAT) was 326.1 μm. Additionally, 21.5% had subretinal fluid (SRF), and 50.5% had hard exudates on presentation. Eyes with ETDRS less than 70 had greater CAT (338.5 μm3 vs. 313.2 μm3; P < .001), greater cube volume (12.2 mm3 vs. 11.3 mm3; P < .001), greater CST (383.5 μm vs. 350.0 μm; P < .001), and SRF (25.5% vs. 17.3%; P = .012). Furthermore, 7.64% had glaucoma, 1.3% had dry age-related macular degeneration, 4.5% of patients were vitrectomized, and 28.7% were pseudophakic. Regarding diabetic stage, 37% had proliferative diabetic retinopathy (PDR) and 63% presented with nonproliferative diabetic retinopathy. Patients presenting with ETDRS less than 70 were more likely to have a history of vitrectomy (7.1% vs. 1.9%, P = .002) and presence of PDR (42.3% vs. 31.4%, P = .004). The results describe a population of patients from a routine clinical practice not entirely represented in clinical trials, with key differences in ocular characteristics seen between VA groups. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:69-75.].