Takahiro Horii

Association Between Hyperreflective Foci in the Outer Retina, Status of Photoreceptor Layer, and Visual Acuity in Diabetic Macular Edema

PURPOSE To determine if hyperreflective foci in the outer retina are associated with photoreceptor integrity and the logarithm of minimal angle of resolution (logMAR) visual acuity (VA) in patients with diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. METHODS Patients (n=76; 108 eyes) with clinically relevant macular edema and no serous retinal detachment were analyzed retrospectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained for all patients. We investigated the relationship between the hyperreflective foci in the outer retinal layers of the external limiting membrane (ELM) at the fovea and the photoreceptor integrity and VA. RESULTS SD-OCT showed that 58 eyes (53.7%) had hyperreflective foci in the outer retinal layers, and 107 eyes (99.1%) had hyperreflective foci in the inner retinal layers. The logMAR VA was significantly (P<.0001) worse in eyes with hyperreflective foci in the outer retinal layers than in eyes without them (0.463±0.382 vs 0.127±0.206, respectively). Disruption of the ELM line on OCT was significantly (P<.0001, for both comparisons) associated with both hyperreflective foci in the outer retinal layers and poor logMAR VA. Disruption of the junction of the inner and outer segment line (IS/OS) also was related to hyperreflective foci in the outer retinal layers and poor logMAR VA (P<.0001 for both comparisons). CONCLUSIONS The presence of hyperreflective foci in the outer retina is closely associated with a disrupted ELM and IS/OS line on SD-OCT images and decreased VA in DME.

Optical Coherence Tomographic Reflectivity of Photoreceptors beneath Cystoid Spaces in Diabetic Macular Edema

PURPOSE To investigate the relationship between the cystoid spaces in the outer plexiform layer (OPL) and the characteristics of the photoreceptors beneath the cystoid spaces in patients with diabetic macular edema (DME). METHODS In this observational cross-sectional study, 123 eyes of 96 consecutive patients with clinically significant macular edema were retrospectively reviewed. The characteristics of the photoreceptors on optical coherence tomography (OCT) images represented by the external limiting membrane (ELM) and the junction between inner and outer segments (IS/OS), and their association with the overlying cystoid spaces were investigated. RESULTS The areas beneath the cystoid spaces in the OPL had a longer transverse length of disrupted or faint IS/OS and disrupted ELM lines than those without cystoid spaces (P < 0.001, P < 0.001, and P = 0.009). The IS/OS lines beneath the cystoid spaces had higher reflectivity than those in areas without cystoid spaces (P < 0.001). Enlarged cystoid spaces extending from the inner nuclear layer to the OPL were associated with disrupted IS/OS or ELM but not faint IS/OS (P < 0.001, P < 0.001, and P = 0.467). The transverse length of disrupted IS/OS at the fovea was correlated with the logarithm of the minimum angle of resolution (logMAR) more than the association between foveal thickness and logMAR (r = 0.49, P < 0.001 vs. r = 0.28, P = 0.002). The ELM descended to the RPE more frequently in eyes with single-lobulated fluorescein pooling in the foveal avascular zone than those with multi-lobulated pooling (P < 0.001). CONCLUSIONS OCT showed that the cystoid spaces in the OPL were accompanied by photoreceptor damage beneath the cystoid spaces in DME.

Optical Coherence Tomographic Evaluation of Foveal Hard Exudates in Patients with Diabetic Maculopathy Accompanying Macular Detachment

OBJECTIVE To study morphologic changes of serous retinal detachment (SRD) and hyperreflective dots, which have been reported to be precursors of hard exudates, detectable in SRD using optical coherence tomography (OCT) to assess whether or not the OCT findings are correlated with the subfoveal deposition of hard exudates in patients with diabetic macular edema (DME) accompanied by SRD. DESIGN Retrospective chart review. PARTICIPANTS Twenty-eight eyes of 19 patients with DME accompanied by SRD. METHODS We imaged SRD and the hyperreflective dots in SRD using spectral domain OCT (SD-OCT). The number and distribution of the hyperreflective dots in SRD were evaluated before the initial treatment at our hospital for DME accompanied by SRD. Based on a difference in the SD-OCT findings, the study eyes were divided into 2 groups: eyes with a few dots and those with many dots. We studied the clinical course of these 2 groups to assess whether or not the findings of SRD and hyperreflective dots on the SD-OCT images were correlated with deposition of hard exudates in the subfoveal space during follow-up. MAIN OUTCOME MEASURES Correlation of the SD-OCT findings of SRD and hyperreflective dots with deposition of hard exudates in the subfovea of patients with DME accompanied by SRD. RESULTS Subfoveal deposition of hard exudates was seen in 11 of the 28 eyes at the final examination. Before initial treatment at our hospital, 14 eyes had a few hyperreflective dots SRD and 14 eyes had many hyperreflective dots. Whereas no deposition of hard exudates in the subfoveal space was seen in the former eyes, it was seen in 11 of the latter 14 eyes (P < 0.0001). In addition, using SD-OCT, we found discontinuity of the outer border of detached neurosensory retina in 9 of the 28 eyes. Of these 9 eyes, 1 was in the group with few hyperreflective dots and eight were in the group with many hyperreflective dots (P = .0046). CONCLUSIONS In patients with DME accompanied by SRD, SD-OCT revealed that hyperreflective dots may be associated with the subfoveal deposition of hard exudates during follow-up.

Foveal cystoid spaces are associated with enlarged foveal avascular zone and microaneurysms in diabetic macular edema.

OBJECTIVE To study the association between pathomorphology at the foveal center delineated by spectral domain optical coherence tomography (SD-OCT) and vascular changes around the fovea in fluorescein angiography (FA) in patients with diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS Consecutive series of 86 eyes from 72 patients with clinically significant macular edema (CSME) on which SD-OCT and FA were performed on the same day. METHODS Fluorescein angiography using HRA2 (Heidelberg Engineering, Heidelberg, Germany) and SD-OCT images using Spectralis OCT (Heidelberg Engineering) were obtained for all patients. Microaneurysms (MAs) in the perifoveal capillary network (PCN) and foveal avascular zone (FAZ) in the FA images were quantified. The pathomorphology at the foveal center was evaluated in OCT images. We then investigated the association between pathologic perifoveal capillaries in FA and the neuroglial morphology in OCT. MAIN OUTCOME MEASURES The relationship between pathologic changes in perifoveal capillaries in FA and foveal pathomorphology in OCT. RESULTS According to the foveal morphology in OCT images, 44 eyes presented foveal cystoid spaces (cystoid macular edema [CME]), 25 eyes had serous retinal detachment (SRD) at the foveal center, and 17 eyes had foveal thickening without cystoid spaces or retinal detachment (retinal swelling). After 3 eyes with ischemic maculopathy were excluded, the relationship was evaluated. The number of MAs in the PCN was significantly greater in eyes with CME (3.20 ± 1.76) than in eyes with SRD (0.40 ± 1.04; P < 0.01) or retinal swelling (0.47 ± 0.72; P < 0.01). In addition, the FAZ in the eyes with CME (0.553 ± 0.323 mm(2)) was significantly larger than that of the eyes with SRD (0.302 ± 0.245 mm(2); P < 0.01) or retinal swelling (0.268 ± 0.142 mm(2); P < 0.01). These associations were found in eyes with thickened posterior hyaloid membranes. CONCLUSIONS The eyes with cystoid spaces at the foveal center delineated by OCT had more MAs in the PCN and larger FAZ in FA images.

Optical Coherence Tomographic Characteristics of Microaneurysms in Diabetic Retinopathy

PURPOSE To characterize microaneurysms in diabetic retinopathy (DR) depicted by spectral-domain optical coherence tomography (SD-OCT). DESIGN Retrospective, observational case series. METHODS We surveyed a consecutive series of 76 eyes from 60 patients with DR (22 mild nonproliferative diabetic retinopathy [NPDR]; 43 moderate NPDR; 9 severe NPDR; 2 proliferative diabetic retinopathy [PDR]) who underwent Spectralis OCT, fluorescein angiography (FA), and color fundus photography on the same day. The microaneurysms on OCT were oval and well demarcated at the points where those on color fundus photographs and FA were delineated. The characteristics of microaneurysms were evaluated. RESULTS Based on the status of the capsular structure shown in the sectional images of OCT (called ring sign), we classified 147 microaneurysms depicted by all of SD-OCT, FA, and color fundus photographs in 76 eyes: 28 with complete ring sign, 54 with incomplete one, and 65 with no structure. Microaneurysms with no ring sign had hyperreflective spots in the lumen and were accompanied by nearby cystoid spaces more frequently than other types (P = .033 and P = .007). Thirteen of 75 microaneurysms with nearby cystoid spaces protruded into the cystoid spaces, and 11 of those 13 microaneurysms presented with no ring sign. Microaneurysms resided mainly in the inner nuclear layer (INL) (80.3%), and 65 of such microaneurysms (55.1%) were accompanied by nearby cystoid spaces. CONCLUSIONS SD-OCT delineated the capsular structure, hyperreflective spots, and location of microaneurysms, and microaneurysms with the ring sign were positively correlated with nearby cystoid spaces and protrusion into the cystoid spaces.

Relationship between Fluorescein Pooling and Optical Coherence Tomographic Reflectivity of Cystoid Spaces in Diabetic Macular Edema

OBJECTIVE To study the characteristics of the reflectivity of the cystoid spaces and serous retinal detachment (SRD) on spectral-domain optical coherence tomography (SD-OCT) and the correlation with fluorescein findings in diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS Consecutive 134 eyes of 114 patients with clinically significant macular edema for whom SD-OCT and fluorescein angiography (FA) were performed on the same day. METHODS Fluorescein angiography using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany) and OCT images using Spectralis OCT (Heidelberg Engineering) were obtained. The reflectivity of the cystoid spaces and SRD on the OCT images was evaluated qualitatively and quantitatively and compared with the fluorescein pooling intensity on FA images. MAIN OUTCOME MEASURES The relationship between the fluorescein pooling and the reflectivity characteristics of the cystoid spaces on SD-OCT images. RESULTS A total of 141 cystoid spaces in 101 eyes were delineated on OCT images, and 138 spaces (97.9%) had fluorescein pooling. Fifty-five cystoid spaces (39.9%) with marked fluorescein pooling intensity had lower reflectivity on OCT images than those with modest pooling (12.1±10.4 vs. 22.0±15.4, P < 0.001). The heterogeneity of the reflectivity of the cystoid spaces on the OCT images was associated significantly (P < 0.001) with modest fluorescein pooling. The hyperreflective foci in the cystoid spaces were correlated significantly with modest fluorescein pooling and higher or heterogeneous reflectivity on OCT images (P < 0.001, P < 0.001, and P=0.005, respectively). In addition, the cystoid spaces with microaneurysms had higher or heterogeneous reflectivity on OCT images more frequently than those without microaneurysms (P < 0.001 and P=0.019, respectively). The reflectivity levels in the SRD were significantly (P=0.005) lower than in the cystoid spaces, and only 1 eye (3.3%) had heterogeneous reflectivity on OCT images. CONCLUSIONS The results provided a novel interpretation of fluorescein pooling and OCT characteristics of cystoid spaces and SRD in DME and suggested several mechanisms by which the blood-retinal barrier is disrupted and concomitant edematous changes develop.

Macular Migration toward the Optic Disc after Inner Limiting Membrane Peeling for Diabetic Macular Edema

PURPOSE To investigate the papillofoveal distance and its association with retinal thickness on optical coherence tomography (OCT) images after vitrectomy for diabetic macular edema (DME). METHODS In this retrospective case series, 72 eyes of 57 consecutive patients who underwent vitrectomy for DME were included. Retinal images dissecting the fovea horizontally were obtained using OCT before and after vitrectomy. After identification of the disc margin and the presumed foveal center, the papillofoveal distance was measured on the OCT images. The association of the distance with retinal thickness and peeling of the inner limiting membrane (ILM) was evaluated. RESULTS The papillofoveal distance was significantly shorter after vitrectomy (3956.1 ± 299.0 μm vs. 3759.6 ± 331.3 μm; P < 0.001), and the shortening was correlated negatively with the total and inner retinal thickness in the temporal subfield (r = -0.29, P = 0.012 and r = -0.34, P = 0.004, respectively). Shortening of the papillofoveal distance was greater in 54 eyes in which ILM peeling was performed compared with 18 eyes in which ILM peeling was not performed (234.7 ± 159.3 μm vs. -9.7 ± 83.5 μm; P < 0.001). No differences were seen in the papillofoveal distance and retinal thickness before and after surgery between eyes with and without preoperative epiretinal membrane or posterior vitreous detachment. The total and inner thicknesses in the temporal subfield were thinner postoperatively in eyes that underwent ILM peeling than those without ILM peeling (P < 0.001 and P < 0.001). CONCLUSIONS The papillofoveal distance on OCT images was shortened and the retina in the temporal subfield was thinner in eyes that underwent ILM peeling to treat DME.

Hyperreflective Foci In Outer Retina Predictive Of Photoreceptor Damage And Poor Vision After Vitrectomy For Diabetic Macular Edema

Purpose: To investigate the correlation between visual outcomes and preoperative hyperreflective foci in the outer retinal layers seen on spectral domain optical coherence tomography images in eyes that underwent vitrectomy for diabetic macular edema. Methods: We retrospectively reviewed 32 consecutive eyes that underwent vitrectomy for diabetic macular edema. Ten eyes had accumulated or many hyperreflective foci in the outer retinal layers preoperatively; 22 eyes did not have the pathology. The logarithm of the minimum angle of resolution and the junction between inner and outer segments were studied in the groups. Results: Logarithm of the minimum angle of resolution was significantly better in eyes without hyperreflective foci than in those with hyperreflective foci at 3 months and 6 months, and the last visit (P = 0.029, 0.010, and <0.001, respectively) compared with no differences at the baseline. Visual improvement was greater in eyes with no hyperreflective foci at the same time points. Seven eyes with hyperreflective foci had no junction between inner and outer segments at the final visit, whereas only 4 eyes with no foci had no junction between inner and outer segments (P = 0.004). However, the foveal thickness did not differ between the groups at any time. Conclusion: Preoperative hyperreflective foci in the outer retinal layers detected by spectral domain optical coherence tomography might predict the photoreceptor damage and a poorer prognosis after vitrectomy for diabetic macular edema.

Association between perifoveal hyperfluorescence and serous retinal detachment in diabetic macular edema.

OBJECTIVE To study the association between the fluorescence levels on fluorescein angiography images and the characteristics on spectral-domain optical coherence tomography (SD OCT) images in diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS One hundred sixty-seven consecutive eyes of 116 patients with diabetic retinopathy for whom FA and SD OCT were performed on the same day. METHODS Fluorescein angiography using the Heidelberg Retina Angiograph 2 and OCT images using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were obtained. The leakage of fluorescein dye in each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid was quantified and defined as fluorescence levels, which were compared with the retinal thickness and foveal pathomorphologic features evaluated by SD OCT. MAIN OUTCOME MEASURES The relationship between fluorescence levels and the foveal pathomorphologic features on SD OCT images. RESULTS One hundred twelve (67%) eyes with center-involved DME had significantly higher fluorescence levels in all subfields of the ETDRS grid than 55 (33%) eyes without DME. Fluorescence levels were correlated modestly with the retinal thickness in individual subfields in eyes with center-involved DME. Thirty-seven eyes with foveal serous retinal detachment (SRD) had greater retinal thickness in all subfields and higher levels of fluorescence in most subfields, except the superior subfield of the inner ring. After adjusting for the central retinal thickness using multivariate analyses, eyes with SRD had significantly (P = 0.0085) higher fluorescence levels in the nasal subfield of the inner ring and the superior, nasal, and inferior subfields of the outer ring (P = 0.0117, P = 0.0020, and P = 0.0017, respectively). However, the fluorescence levels in any subfields of the inner or outer ring did not differ significantly between eyes with and without foveal cystoid spaces. CONCLUSIONS The correlation between the fluorescence levels and retinal thickness suggests that the vascular hyperpermeability in the perifovea contributes to the pathogenesis of foveal SRD in DME.

Qualitative and Quantitative Characteristics of Near-Infrared Autofluorescence in Diabetic Macular Edema

OBJECTIVE To study the characteristics of near-infrared autofluorescence (NIR-AF) imaging and its association with spectral-domain optical coherence tomography (SD-OCT) findings and logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) in diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS One hundred twenty-one consecutive eyes of 87 patients with center-involved DME for whom NIR-AF and SD-OCT images of sufficient quality were obtained. METHODS The NIR-AF images were acquired using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany), and sectional retinal images were obtained using Spectralis OCT (Heidelberg Engineering). The presence of a mosaic pattern and cystoid signs were determined qualitatively. We quantified the average fluorescence intensity in the central 1-mm subfield. The characteristics of the NIR-AF images were compared with the OCT findings and logMAR VA. MAIN OUTCOME MEASURES Qualitative and quantitative characteristics of the NIR-AF images and their association with SD-OCT findings and logMAR VA. RESULTS Fifty-seven eyes with a mosaic pattern in the NIR-AF macular images had worse logMAR VA (0.355±0.239 vs. 0.212±0.235; P = 0.001), a thicker central subfield (CSF) (530±143 μm vs. 438±105 μm; P <0.001), and disrupted external limiting membrane (ELM; P <0.001) compared with 64 eyes without these findings. Forty-one eyes with a cystoid sign in the NIR-AF images had worse logMAR VA (0.393±0.233 vs. 0.221±0.234; P <0.001) and a thicker CSF (557±155 μm vs. 443±100 μm; P <0.001) than those without them; there were no significant differences in the ELM status. The relative fluorescence intensity in the central subfield in the NIR-AF images was correlated negatively with the CSF thickness and logMAR VA (R = 0.492, P <0.001 and R = 0.377, P <0.001, respectively). Eyes with foveal serous retinal detachment had lower levels of relative fluorescence intensity than those without it (0.751±0.191 vs. 0.877±0.154; P = 0.007); there was no association with the presence of foveal cystoid spaces, disrupted ELM, or hyperreflective foci in the outer retinal layers. CONCLUSIONS Novel qualitative and quantitative NIR-AF characteristics in the macula indicated the clinical relevance and suggested the pathogenesis in DME.