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To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

We created three types of vessel models: vessel volume, surface, and line models from swept-source optical coherence tomography images and tested experimentally calculated three-dimensional (3D) biomarkers. The choroidal volume (CVolume), surface area (VSurface), and vessel length-associated index (VLI) were measured. The calculated 3D parameters were the mean choroidal thickness, choroidal vascularity index (CVI), vessel length density index (VLDI), vessel length to the stromal (VL–S) ratio, surface-to-volume ratio (S–V ratio), and vessel diameter index (VDI). Cluster analysis showed that the parameters were classified into two clusters: one was represented by the VVolume including the CVolume, VSurface, CVI, S–V ratio, VLI, VDI, and subfoveal choroidal thickness and the other by the VL–S ratio including the VLDI. Regarding the regional distribution, the VVolume, CVolume, VSurface, CVI, VLI, VL–S ratio, and VDI at the foveal center were higher than at the parafovea (P

Purpose To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. Methods Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. Results Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p Conclusion The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

BACKGROUND: To propose a modified method to investigate the flow void of polypoidal choroidal vasculopathy (PCV) choriocapillaris. METHODS: This paper involves a retrospective study. Included 30 PCV affect eyes, 30 old control eyes, 20 young control eyes, 15 affect eyes with anti-VEGF intravitreal injection treatment, and 8 fellow eyes of anti-VEGF intravitreal injection treatment group. After the choriocapillaris slab [10 µm thick starting 30 µm beneath to the retinal pigment epithelium (RPE)-fit reference] was extracted from macular optical coherence tomography angiography 6×6-mm scans, the flow void was segmented by the Phansalkar method. We analyzed the flow void sizes-frequency histogram in order to investigate the differences of flow void proportion between groups. Then we verified the differences between groups after anti-VEGF intravitreal injection treatment. RESULTS: On the difference curve between the PCV group and Old control group, there was a peak appeared at the flow void sizes range from 900 to 1,125 µm(2). The average number of flow void sizes from 900 to 1,125 µm(2) was significantly higher in the Old control group than that in the Young control group (P

Observation of choroidal thickness after anti-vascular endothelial growth factor (VEGF) therapy may be important for the ideal management of neovascular age-related macular degeneration (AMD). This study investigated changes in subfoveal choroidal thickness (SCT) during loading doses of intravitreal injections of brolucizumab in eyes with neovascular AMD.This study included 73 eyes of 72 patients with neovascular AMD at five university hospitals in Japan. All 73 eyes underwent three monthly 6.0 mg intravitreal injections of brolucizumab at baseline, 1 month, and 2 months. The SCT at 3 months was evaluated using optical coherence tomography.The 73 eyes were classified into the treatment-naïve group (43 eyes) and the switched group (30 eyes) that were switched from other anti-VEGF treatments. After three intravitreal injections of brolucizumab, SCT significantly decreased from 236.5 ± 98.8 µm at baseline to 200.4 ± 98.3 µm at 3 months (percent of baseline 84.7%, P 0.001) in the treatment-naïve group. In the switched group, SCT also significantly decreased from 229.0 ± 113.2 μm at baseline to 216.9 ± 110.2 μm at 3 months (percent of baseline 94.7%, P = 0.039), although the decrease was not as marked compared to that of the treatment-naïve group.Intravitreal injections of brolucizumab for neovascular AMD significantly reduced the SCT in both the treatment-naïve and switched groups. Brolucizumab may cause significant anatomic changes in the choroid, particularly in treatment-naïve AMD eyes, possibly more than that previously reported for other anti-VEGF agents.

To evaluate the morphological characteristics of the flow void (FV) in the fellow eyes of the unilateral polypoidal choroidal vasculopathy (PCV). 52 eyes of PCV fellow eyes (PCVF) and 57 age-matched normal controls were recruited in this prospective study. The number of FV was analyzed according to the size which from 6×6-mm swept source optical coherence tomography angiography scans. We used indocyanine green angiography images to determine whether choroidal vascular hyperpermeability (CVH) has occurred. For the PCVF, the incidence of CVH was 70% (35 of 50. Two of participants were allergic to the dye.) The number of FV significantly lower in all sizes (P = .002), 400 ~ 500µm2 (P = .002), 525 ~ 625µm2 (P = .002) and 650 ~ 750µm2 (P = .005). And the distribution significantly different in all sizes (P = .002), 400 ~ 500µm2 (P = .001), 525 ~ 625µm2 (P = .002) and 650 ~ 750µm2 (P = .001) compared to the controls. And showed no differences in the size from 775 to 1125µm2 between two groups. The area under the receiver operating characteristic curve of PCVF with CVH and controls was 0.93 (95% CI: 0.88 ~ 0.98) (P

Background To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD). Methods Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years. Results Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 μm at baseline, 151 ± 38 μm (P P P P Conclusion Long-term aflibercept injection can achieve visual improvement and reduce the thickness of the retina and choroid in nAMD. Morphological improvement of these tissues may not be sufficient to sustain earlier visual improvement over the long-term.

The choroid is a complex vascular tissue that is covered with the retinal pigment epithelium. Ultra high speed swept source optical coherence tomography (SS-OCT) provides us with high-resolution cube scan images of the choroid. Robust segmentation techniques are required to reconstruct choroidal volume using SS-OCT images. For automated segmentation, the delineation of the choroidal-scleral (C-S) boundary is key to accurate segmentation. Low contrast of the boundary, scleral canals formed by the vessel and the nerve, and the posterior stromal layer, may cause segmentation errors. Semantic segmentation is one of the applications of deep learning used to classify the parts of images related to the meanings of the subjects. We applied semantic segmentation to choroidal segmentation and measured the volume of the choroid. The measurement results were validated through comparison with those of other segmentation methods. As a result, semantic segmentation was able to segment the C-S boundary and choroidal volume adequately.

A patient with HELLP syndrome showed bilateral extensive serous retinal detachment. Choroidal thickening and ground glass appearance of choroidal vessels was noticed on the optical coherence tomography (OCT) images. Choroidal morphology on the OCT images may be useful as an adjunctive and noninvasive finding to establish a diagnosis of HELLP syndrome., Purpose: We report here, the morphological characteristics of the retina and choroid in a patient with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, who was not aware of her pregnancy before visiting our hospital. Methods: Case report. Results: The patient complained of visual disturbances in both eyes for a few days. Extensive serous retinal detachment and hyperreflective foci were observed in both eyes on spectral domain optical coherence tomography (SDOCT). Enhanced depth imaging technique using SDOCT revealed choroidal thickening and unclear choroidal vessel contour. Her blood pressure was 230/168 mmHg. Laboratory data showed hemolysis and liver dysfunction. Obstetrical examination disclosed her pregnancy. She was diagnosed as having HELLP syndrome. Because her general condition improved after prompt Cesarean delivery, the fundus lesions were rapidly resolved with choroidal thinning. Conclusion: The eyes in a patient with HELLP syndrome showed characteristic choroidal morphology. The choroidal morphology shown with SDOCT might be one of the pathognomonic signs for a diagnosis of HELLP syndrome.

Purpose To investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD). Methods This was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen. This study included a total of 105 eyes. Aqueous humor samples were collected from 25 eyes with PNV without polyps, 23 eyes with PCV, and 24 eyes with drusen-associated nAMD before intravitreal anti-vascular endothelial growth factor (VEGF) injection and cataract surgery in 33 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, C5a, VEGF, and macrophage chemoattractant protein 1 (MCP-1) using a bead-based immunoassay. Results C3a and MCP-1 levels were significantly higher in PCV (P = 0.032 and P = 0.039, respectively) and drusen-associated nAMD (P = 0.01 for both comparisons) than in controls, and no difference was seen in C3a and MCP-1 levels between PNV and controls (P = 0.747 and P = 0.294, respectively). VEGF levels were significantly higher in PNV (P = 0.016), PCV (P = 0.009), and drusen-associated nAMD (P = 0.043) than in controls. In PNV, the VEGF levels elevated without elevated C3a and MCP-1. Conclusions PNV, PCV, and drusen-associated nAMD had significantly distinct profiles of complement activation products and cytokines in the aqueous humor.

The complement system may be activated in the posterior segment of the eye with chorioretinal disease, which may be reflected to the concentration of anaphylatoxins in the aqueous humor. Little is known about the distribution of anaphylatoxins in the aqueous and vitreous humor. The aim of the present study was to investigate the distribution of anaphylatoxin concentration in the aqueous and vitreous humor of the eyes with idiopathic epiretinal membrane or idiopathic macular hole. This was an experimental, observational case series. This study included 43 eyes from 43 patients; 29 eyes with idiopathic epiretinal membrane, and 14 eyes with idiopathic macular hole. All 43 eyes underwent cataract surgery and vitrectomy. The aqueous and vitreous humor were collected at the surgery. The anaphylatoxin concentrations were measured by using a cytometric beads array, and the respective C3a, C4a, and C5a concentrations were 2.003 ± 0.679 (mean ± standard deviation) ng/ml, 1.389 ± 0.419 ng/ml, and 0.003 ± 0.004 ng/ml in the aqueous humor, and 1.236 ± 0.642 ng/ml, 1.250 ± 0.542 ng/ml, and 0.048 ± 0.069 ng/ml in the vitreous humor. The mean C3a concentration in the aqueous humor was significantly higher than in the vitreous humor in 43 eyes of iMH and iERM (P 0.001). The mean C4a concentration showed no significant difference between the aqueous humor and vitreous humor (P = 0.282), and the mean C5a in the aqueous humor was significantly lower than in the vitreous humor overall (P 0.001). The C3a concentration in the aqueous humor strongly correlated with that in the vitreous humor (R = 0.510, P 0.001). The concentrations of C4a and C5a in the aqueous humor moderately correlated with those in the vitreous humor (C4a; R = 0.356, P = 0.019, C5a; R = 0.464, P = 0.022). In conclusion, the anaphylatoxin concentrations measured by cytometric beads array in the aqueous humor may be associated with those measured in the vitreous humor.

Purpose To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). Methods Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. “Close” was defined as the portion within 1 degree from the border of any abnormal FAF, and “Distant” was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. Results We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF (“Distant”: p

Yukinori Sugano, Tetsuju Sekiryu, Minoru Furuta, Ryutaro Tomita, Hiroaki Shintake, Hiroki Maehara, Akira Ojima Department of Ophthalmology, Fukushima Medical University, Fukushima, Japan Purpose: To assess the reproducibility of quantitative morphometrical evaluation of the choriocapillaris imaged with swept-source optical coherence tomography angiography (SS-OCTA).Subjects and methods: This observational, cross-sectional case series included 35 eyes of healthy individuals and 32 eyes of 32 patients. Two images of the fovea were taken using SS-OCTA with 3×3 mm squares. Images of the choriocapillaris within 800×800 pixel squares centered at the fovea were analyzed morphometrically using open-source software “AngioTool” that applies a Gaussian recursive filter and multiscale Hessian enhancement. This program’s vessel thickness and intensity parameters can be changed to aid vessel detection. We measured the pairs of images per eye with different parameter sets and calculated the intraclass correlation (ICC) for the morphometrical results. After determining the parameters that produced high reproducibility, we evaluated regional variations in 800×800 pixel mm squares within the fovea.Results: The ICCs for vessel area, total vessel length, vessel diameter index, and mean lacunarity were over 0.9 using the parameters of “vessel thickness” 3–4 and intensity 15 in the group including all subjects. When measurements were performed using these same parameter values, the vessel density and mean vessel diameter index were 60.5% and 19.1±0.389, respectively. Vessel density, vessel length, vessel diameter index, and mean lacunarity did not change significantly within an 800×800 pixel square centered at the fovea except for the 200×200 pixel square at the foveal center.Conclusion: SS-OCTA images of the choriocapillaris can be measured with high reproducibility by morphometrical evaluation using open-source software with multiscale Hessian enhancement. Such automated morphometric analysis can provide an objective evaluation of the choriocapillaris. Keywords: choriocapillaris, swept-source optical coherence tomography angiography, morphometry, vessel density

PurposeAbnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.MethodsSixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as "within," "close," and "distant," based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.ResultsIn Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (pConclusionIn Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

PURPOSE To evaluate the subfoveal choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in patients with retinal angiomatous proliferation. METHODS Subfoveal choroidal thickness was retrospectively measured using enhanced depth imaging optical coherence tomography. RESULTS Thirty-two eyes of 26 patients (average age, 82 years) with newly diagnosed retinal angiomatous proliferation were examined. All eyes were treated with intravitreal ranibizumab and photodynamic therapy. In 14 eyes without recurrence over 6-month follow-up (average, 8.4 months), mean subfoveal choroidal thickness decreased from 198 μm at baseline to 169 μm (85.4%) at 3 months and to 173 μm (87.3%) at 6 months after treatment (P < 0.01 compared with baseline, respectively). In 18 eyes with recurrence over 3-month follow-up, mean subfoveal choroidal thickness decreased from 199 μm at baseline to 171 μm (85.9%) at 3 months after treatment and 176 μm (88.4%) even at recurrence (P < 0.01 compared with baseline, respectively). CONCLUSION Subfoveal choroidal thickness after intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation decreased to approximately 85% compared with baseline by 3 months after treatment, and the trend persisted in eyes with or without recurrence during follow-up. This may indicate that choroidal changes are not associated with recurrence in retinal angiomatous proliferation.

Purpose To investigate the longitudinal morphologic choroidal changes in eyes with acute zonal occult outer retinopathy. Methods In this retrospective observational case series, we studied 10 patients (11 eyes) with unilateral acute zonal occult outer retinopathy at the first visit who were followed more than 12 months by enhanced depth optical coherence tomography. The retinal and choroidal thicknesses (CTs) were measured at six sites in the macula. Results The integrity of the ellipsoid zone was lost 1,500 μm and 3,000 μm nasally in all 11 eyes at the first visit. Compared with the unaffected fellow eyes, the mean total retinal thickness at the first visit was significantly (P = 0.03) thinner 3,000 μm nasal to the fovea in the affected eyes. The mean CTs in the affected eyes did not differ from that in the unaffected eyes at any evaluation; the mean subfoveal CT in the affected eyes gradually decreased during the follow-up period. Compared with the first visit, the mean subfoveal CT decreased significantly (P = 0.011) at the foveal center and nasal, superior, and temporal to the fovea 12 months after disease onset. Conclusion The subfoveal CT in eyes with acute zonal occult outer retinopathy can decrease during follow-up.

Purpose: To investigate the relationship between subfoveal choroidal thickness and axial length in Japanese preschool children with hyperopic anisometropic amblyopia. Methods: Twenty-four children between the age of 3 and 6 years exhibiting hyperopic anisometropic amblyopia were examined. Differences in spherical equivalent between the two eyes were over 1.5 D in all children. Twenty-four eyes in 12 children without anisometropia and amblyopia were examined as age-matched normal controls. Subfoveal choroidal thickness was measured by using enhanced depth imaging optical coherence tomography. Axial length was measured with noncontact optical biometer. Results: The spherical equivalent ranged from +3.50 to +7.25 D in amblyopic eyes and from +0.75 to +3.50 D in fellow eyes. The subfoveal choroidal thickness was significantly greater in the amblyopic eyes than that in the fellow eyes (407.3 ± 54.2mm versus 357.7 ± 54.3mm, Paired t-test, p50.05). The axial length in the amblyopic eyes was significantly shorter than that in the fellow eyes (21.16 ± 0.64 mm versus 22.08 ± 0.72 mm, Paired t-test, p50.05). The mean choroidal thickness of the fellow eyes in hyperopic anisometropic amblyopia was greater than that in age matched normal children, although this difference did not reach statistical significance (326.0 ± 62.1mm, p = 0.07). The subfoveal choroidal thickness in amblyopic children was negatively correlated with their axial length (r =0.50, p50.01). Conclusion: The subfoveal choroidal thickness of amblyopic children abnormally increased and the thicker subfoveal choroid is mildly correlated with their shorter axial length. The anomalous subfoveal choroidal thicknesses in our amblyopic children may reflect a delay in emmetropization.

To evaluate meibomian gland loss after trabeculectomy with mitomycin C (MMC). This cross-sectional observational case study involved 55 eyes in 39 patients who had undergone trabeculectomy with MMC administered to the upper area of the eye. We used a mobile pen-shaped noncontact meibography system to access the morphology and determine loss of the meibomian glands. Meibomian gland loss was scored (meiboscore) from grade 0 (no loss of the meibomian glands) through grade 3 (loss of more than two-thirds of the total area) in the bleb-contacting and bleb-noncontacting upper eyelid areas in the primary position and in the lower eyelid. The tear film breakup time (BUT) was also measured. The median duration from trabeculectomy to examination was 7.4 years (interquartile range 3.1–14.2). The meiboscores of the bleb-contacting upper eyelid areas were significantly higher than those for the bleb-noncontacting upper eyelid areas (P

Purpose To create hybrid three-dimensional (3D) models of the choroidal vasculature from swept-source optical coherence tomography (SS-OCT) angiography images and to evaluate the model's characteristics. Methods This study used prospective, noncomparative case series, including 21 eyes of 21 healthy individuals. The 6 × 6-mm macular area was imaged repeatedly to obtain two cube image sets. Images from structural OCT (OCT-S) and OCT angiography (OCT-A) were exported. After vessel-like structures segmentation from the inverted black and white OCT-S images and the OCT-A images, both types of images were reconstructed in a 3D model. The volumes of the outer choroid and the choroidal vessels were measured after thresholding. The similarities of the segmented choroidal vessels (between OCT-S and OCT-A) and between repeatedly acquired images were measured. Results Mean vessel volume was 2.227 mm3 (29% of the outer choroidal volume) in OCT-S and 0.848 (11%) in OCT-A when measured after removal of the choriocapillaris equivalent volume. Three percent of the vessel volume in OCT-S and 8.4% of that in OCT-A overlapped. The Dice similarity coefficient of vessel volumes in repeated images from the same individual was 0.863 in OCT-S and 0.485 in OCT-A. The ratio of vessel volume to the outer choroidal volume was invariant in OCT-S but increased in OCT-A in the eyes with long axial length. Conclusions Hybrid 3D vascular models of the choroidal vasculature were reconstructed from OCT-S and OCT-A. The new models should prove useful for volumetric analysis of the choroid. Translational relevance Hybrid 3D models of the choroidal vasculature enable volumetric analysis and facilitate morphologic evaluation.

To evaluate subfoveal choroidal thickness changes in cases with recurrent polypoidal choroidal vasculopathy (PCV) after combination therapy with intravitreal ranibizumab and photodynamic therapy (PDT).Retrospective observational case series study.We measured subfoveal choroidal thickness in PCV using optical coherence tomography (OCT) before and after PDT. In recurrent cases, the choroidal thickness was measured at the time of the recurrence. In nonrecurrent cases, choroidal thickness was measured 1 year after PDT.Combination therapy was performed in 27 eyes (27 patients). Polypoidal lesions regressed within 3 months after initial treatment in all eyes. Retreatment was needed in 10 of 27 eyes (37.0%) after more than 3 months of follow-up. In recurrent cases, subfoveal choroid decreased from 188 μm at baseline to 157 μm 3 months after PDT (P.01); however, choroidal thickness increased to 179 μm with recurrence (P = .54 compared to baseline; average, 8.0 months). In nonrecurrent cases, subfoveal choroid decreased from 257 μm at baseline to 210 μm 3 months after PDT and 212 μm 1 year after PDT (P.01, respectively).Subfoveal choroidal thickness in PCV at the time of recurrence returned to the baseline level after choroidal thinning as a result of PDT treatment. Choroidal thickness changes after PDT examined using OCT may reflect disease activity in PCV.

Purpose: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. Procedures: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. Results: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). Conclusions: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.

Idiopathic macular telangiectasia (MacTel) is classified into aneurysmal telangiectasia (type 1), perifoveal telangiectasia (type 2) and occlusive telangiectasia (type 3). Most instances of telangiectasia in Western countries are type 2. This study reports clinical and demographic features of MacTel in Japanese patients. Newly diagnosed patients with MacTel were examined retrospectively. All patients underwent fluorescein angiography and optical coherence tomography. Thirty-four eyes of 27 patients with MacTel were included. Twenty eyes of 20 patients (74.1%) had type 1, ten eyes of five patients (18.5%) had type 2, and four eyes of two patients (7.4%) had type 3. Foveal capillary dilatation and microaneurysms were observed in all except for one eye of early stage type 2 MacTel. Optical coherence tomography revealed cystoid macular edema in type 1, temporal foveal thinning and a loss of boundary between the inner and outer segments of photoreceptors in type 2, and thinning of all retinal layers around the fovea in type 3. The most frequent among our patients was aneurysmal MacTel, whereas perifoveal MacTel was not common. Although the clinical characteristics were similar, the most common type was different from that in Western countries.

To retrospectively evaluate choroidal thickness 1 year after photodynamic therapy in eyes with central serous chorioretinopathy using optical coherence tomography.Central serous chorioretinopathy was diagnosed using fluorescein angiography, and indocyanine green angiography was used to evaluate choroidal vascular hyperpermeability. We measured the subfoveal choroidal thickness using enhanced depth imaging optical coherence tomography.Thirteen eyes (13 patients; average age, 56.8 years) with central serous chorioretinopathy were observed 1 year after half-dose photodynamic therapy with verteporfin. The mean subfoveal choroidal thickness decreased significantly from 397 ± 108 μm at baseline to 323 ± 120 μm at 1 month, 312 ± 117 μm at 3 months, 317 ± 117 μm at 6 months, and 321 ± 122 μm at 1 year (P0.01, for each comparison with baseline). However, the subfoveal choroid thickness significantly increased 2 days after photodynamic therapy to 441 ± 120 (P0.01) compared with baseline. Central serous chorioretinopathy did not recur in any patient. Indocyanine green angiography images at 3 months showed less choroidal vascular hyperpermeability compared with baseline.Half-dose photodynamic therapy for central serous chorioretinopathy resulted in thinner subfoveal choroidal thickness 1 month after treatment, decreased the choroidal vascular hyperpermeability, and maintained the remission for 1 year. Enhanced depth imaging optical coherence tomography was helpful for monitoring the pathophysiologic choroidal changes in central serous chorioretinopathy.

To evaluate the subfoveal choroidal thickness in Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography.Retrospective observational study. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography, in which the optical coherence tomography instrument was placed close enough to the eye to obtain an inverted image, which was averaged for 100 scans. All patients were diagnosed as having the ocular findings of VKH disease with or without extraocular disorders. The patients were followed during their initial treatment with corticosteroids.All 8 patients (16 eyes) with acute phase VKH disease presented with thickening of the choroid. The serous retinal detachment disappeared in 1 month after corticosteroid treatment. The mean choroidal thickness in 16 eyes decreased from 805 ± 173 μm at the first visit to 524 ± 151 μm at 3 days (P0.001) and 341 ± 70 μm by 2 weeks (P0.001).Patients with active VKH disease have markedly thickened choroids, possibly related not only to inflammatory infiltration but also to increased exudation. Both the choroidal thickness and the exudative retinal detachment decreased quickly with corticosteroid treatment. Enhanced depth imaging optical coherence tomography can be used to evaluate the choroidal involvement in VKH disease in the acute stages and may prove useful in the diagnosis and management of this disease noninvasively.

PURPOSE To evaluate the subfoveal choroidal thickness before and after treatment in papillitis type of Vogt-Koyanagi-Harada (VKH) disease and idiopathic optic neuritis (ON) using enhanced depth imaging spectral domain optical coherence tomography. METHODS A total of 11 eyes of 7 patients (average age 47.3 years old) with papillitis type of VKH disease and 11 eyes of 8 patients (average 36.4 years old) with idiopathic ON case were included. The subfoveal choroidal thickness before and 1 month after treatment was measured using enhanced depth imaging spectral domain optical coherence tomography technique. Diagnosis was defined using fluorescein and indocyanine green angiography for VKH disease and magnetic resonance imaging for ON. Either case was treated with systemic steroid therapy. RESULTS The mean subfoveal choroidal thickness before treatment in papillitis type of VKH disease was significantly thicker than in idiopathic ON case (527 ± 119 μm vs. 321 ± 86 μm, P < 0.01). Choroidal thickness in papillitis type of VKH disease decreased significantly to 313 ± 91 μm 1 month after treatment (P < 0.01, as compared with baseline), whereas choroidal thickness in idiopathic ON case remained about the same (319 ± 89 μm, P = 0.62, as compared with baseline). CONCLUSION Although papillitis type of VKH disease is often misdiagnosed as idiopathic ON case, the initial choroidal thickness and its change after treatment may be useful in the differential diagnosis and management.

To evaluate the retinal and choroidal thickness changes following intravitreal ranibizumab injection (IVR) for exudative age-related macular degeneration (AMD).Twenty-eight eyes of 28 patients (average age 72.2) with newly diagnosed AMD (typical AMD 24 and PCV 4) were retrospectively examined during a 1-year follow-up. All cases first received 3 consecutive monthly injections and thereafter pro re nata (PRN) retreatment. Central retinal thickness and subfoveal choroidal thickness were measured before and 1, 3, 6 and 12 months after initial treatment using optical coherence tomography.The average number of injections was 5.2 times. Mean central retinal thickness significantly decreased from 456 microm at baseline to 337 microm 1 month after IVR and 280 microm 1-year after initial IVR (respectively, p0.01). Mean subfoveal choroidal thickness was 225 microm (typical AMD was 227 microm at baseline) at baseline, 225 microm 6 months after initial IVR and 220 microm 1-year after initial IVR. There was no significant difference compared to baseline (p = 0.78 and 0.45).Although central retinal thickness of AMD decreased even 1-year after initial IVR, subfoveal choroidal thickness remained at 6 months and 1-year after initial IVR. Subfoveal choroidal thickness of AMD is less affected by IVR in the long term.

To evaluate changes in choroidal thickness adjacent to the area of laser application after photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV) using enhanced depth imaging spectral-domain optical coherence tomography. Masked observers measured the choroidal thickness at the subfovea and superior, inferior and temporal areas adjacent to the area of laser application before, 2 days, 1 week and 1 and 3 months after treatment. Thirty-seven patients with PCV treated with PDT with verteporfin were included. The mean subfoveal choroidal thickness decreased significantly (P

Purpose. To describe the findings of fundus autofluorescence (FAF) and optical coherence tomography (OCT) in patients with branch retinal vein occlusion (BRVO).Methods. In this institutional, retrospective, observational case series, FAF was evaluated in 65 eyes with BRVO in 64 consecutive patients and compared with visual acuity, OCT findings, and other clinical observations.Results. Five types of autofluorescence appeared during the course of BRVO: (1) petaloid-shaped hyperautofluorescence in the area of macular edema and (2) hyperautofluorescence coincident with yellow subretinal deposits. (3) Diffuse hyperautofluorescence appeared within the area of serous retinal detachment (SRD) and OCT showed precipitates on the undersurface of the retina in 5/5 of these eyes (100%). (4) The area of vein occlusion showed diffuse hyperautofluorescence after resolution of the retinal bleeding. (5) Hard exudates exhibited hyper- or hypoautofluorescence. OCT indicated that most of the hard exudates with hyperautofluorescence were located on the retinal pigment epithelium.Conclusions. Hyperautofluorescence associated with subretinal fluid or hard exudate appeared in the subretinal space. This type of hyperautofluorescence may be attributed to blood cell or macrophages. FAF and OCT are noninvasive modalities that provide additional information regarding macular edema due to BRVO.

PURPOSE: To evaluate the macular choroidal and scleral changes in tilted disc syndrome (TDS) with staphyloma using optical coherence tomography (OCT) to determine the mechanism of serous retinal detachment (SRD) formation. METHODS: All eyes underwent fluorescein (FA) and indocyanine green angiography (ICGA) in this retrospective, observational study. Enhanced-depth imaging (EDI) OCT and prototype high-penetration (HP) OCT were used to examine the choroid and sclera, respectively, at the upper and lower optical areas and the subfovea on vertical OCT sections. RESULTS: Twenty-four eyes with TDS with inferior staphyloma were included. FA showed the macular area with the superior edge of staphyloma had a granular hyperfluorescent pattern and ICGA showed belt-like hypofluorescence. OCT showed SRDs in seven eyes. The mean EDI-OCT choroidal thicknesses in 19 eyes were: upper area, 211 ± 79 μm; subfovea, 153 ± 70 μm; and lower area, 158 ± 42 μm. The mean subfoveal and lower choroid were significantly (P < 0.01 for both) thinner than the upper area. The mean HP-OCT scleral thicknesses in 14 eyes were: upper area, 414 ± 36 μm; subfovea, 493 ± 40 μm; and lower area, 398 ± 83 μm. The subfoveal sclera was significantly (P < 0.01) thicker than the others. CONCLUSIONS: The subfoveal choroid was relatively thin and the subfoveal sclera thickened in TDS with a staphyloma edge at the macula. The area with retinal pigment epithelial (RPE) atrophy was hyperfluorescent on FA; choriocapillaris occlusion was hypofluorescent on ICGA. Characteristic anatomic subfoveal scleral alterations might lead to a thinner choroid and inhibit chorioscleral outflow; a secondary RPE disorder subsequently could cause SRDs.

Purpose: To evaluate the subfoveal choroidal thickness in the fellow eyes of patients with CSC, a disease often associated with choroidal vascular hyperpermeability even in eyes without subretinal fluid. Methods: In this observational cross-sectional study, we measured the bilateral subfoveal choroidal thickness in patients with unilateral CSC using enhanced depth imaging spectral-domain optical coherence tomography. Areas of choroidal vascular hyperpermeability were visualized with indocyanine green angiography. Results: Sixty-six consecutive Japanese patients (50 men, 16 women; mean age, 52.8 years) with unilateral CSC were examined. The subfoveal choroid in symptomatic eyes was significantly thicker than that in fellow eye (414 ± 109 μm vs. 350 ± 116 μm, P < 0.001, respectively). The subfoveal choroid of eyes with choroidal vascular hyperpermeability was 410 ± 92 μm, which differed significantly (P < 0.001) from the choroid (239 ± 59 μm) of fellow eyes without choroidal vascular hyperpermeability. Conclusion: The subfoveal choroid in the fellow eyes of patients with CSC was thicker in the eyes with choroidal vascular hyperpermeability. Enhanced depth imaging spectral-domain optical coherence tomography can assess the effects of choroidal vascular hyperpermeability by measuring the choroidal thickness noninvasively.

Purpose To investigate functional abnormalities in eyes with central serous chorioretinopathy (CSC). Design Observational case series. Methods Sixteen eyes with CSC were enrolled. Autofluorescence densitometry was performed to measure the optical density of the photopigments. Serial fundus autofluorescence (FAF) images were obtained by Heidelberg Retina Angiogram 2. We calculated the autofluorescence optical density difference from the FAF images. To compare the distribution pattern of autofluorescence optical density difference to the findings of outer retina, spectral-domain optical coherence tomography (SD-OCT) was performed in the acute phase and after resolution of CSC. Results The autofluorescence optical density difference decreased at the serous retinal detachment (SRD) in all 16 eyes. After resolution, the photoreceptor inner and outer segment junction (IS/OS) was irregular in 13 eyes and defective in 3 eyes on SD-OCT. The autofluorescence optical density difference did not improve in any eyes. Five eyes were reexamined 3 month after resolution. In 4 of the 5 eyes, SD-OCT showed that the IS/OS was well delineated and 1 eye defective. The autofluorescence optical density difference improved in 2 of the 4 eyes, but not in the other 2 eyes. In the 1 eye without well-delineated IS/OS, the autofluorescence optical density difference did not improve. Conclusion In eyes with CSC, the photopigment density decreased at the SRD. The density remained decreased immediately after resolution and showed delayed recovery. The photopigments decreased even in eyes with morphologic recovery of the outer retina.

Purpose To evaluate the subfoveal choroidal thickness after treatment of central serous chorioretinopathy (CSC) visualized by enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT) and indocyanine green angiography (ICGA). Design Retrospective, comparative series. Participants Twenty patients (20 eyes). Methods The subfoveal choroidal thickness and height of the serous retinal detachment before and after treatment was measured using EDI OCT. Areas of choroidal vascular hyperpermeability were visualized with ICGA. Eyes with classic CSC were treated with laser photocoagulation (LP), whereas eyes with chronic CSC, which are not amenable to LP, were treated with half-dose verteporfin photodynamic therapy (PDT). Main Outcome Measures Change in choroidal thickness and height of the serous retinal detachment after treatment. Results There were 12 eyes in the LP group and 8 eyes in the PDT group. The serous subretinal fluid resolved in both groups after treatment. In the LP group, the mean choroidal thickness was 345±127 μm at baseline and 340±124 μm at 4 weeks, a difference that was not significant ( P = 0.2). The mean choroidal thickness in the PDT group increased significantly from 389±106 μm at baseline to 462±124 μm ( P = 0.008) by 2 days after treatment, and then reduced rapidly to 360±100 μm ( P = 0.001) at 1 week and 330±103 μm ( P Conclusions The subretinal fluid resolved in both disease groups; however, the choroidal thickness and hyperpermeability seen during ICGA was reduced after PDT. These findings suggest that PDT reduces the choroidal vascular hyperpermeability seen in CSC and may work by a different mechanism than LP. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Mariko Kano, Tetsuju Sekiryu, Yukinori Sugano, Yasuharu Oguchi, Akira Ojima, Kanako Itagaki, Masaaki Saito Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Japan Purpose: To evaluate the efficacy of monthly injections of aflibercept and ranibizumab on foveal structure after three months, for the treatment of occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD).Methods: We retrospectively studied 103 eyes with treatment-naïve neovascular AMD with occult and no classic CNV. Seventy-four of 103 eyes were treated with ranibizumab (intravitreal ranibizumab injection [IVR] group); 29 eyes were treated with aflibercept (intravitreal aflibercept injection [IAI] group). The best-corrected visual acuity and the retinal and choroidal structure at the fovea were evaluated using optical coherence tomography.Results: The total foveal thickness, the height of serous retinal detachments, and subfoveal choroidal thickness were compared with baseline, and the incidence of retinal pigment epithelial elevation significantly decreased in the IAI group compared with the IVR group. In contrast, the thickness of the sensory retina at the fovea significantly decreased in the IVR group when compared with the IAI group. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity improved more significantly in the IVR group (-0.085±0.164) than in the IAI group (-0.020±0.125) at 3months (P=0.017).Conclusion: After intravitreal injection, aflibercept more rapidly reduced subretinal fluid and subfoveal choroidal thickness. In contrast, ranibizumab decreased the sensory retinal thickness compared with aflibercept. The responses of the retinal and choroidal tissue to these anti-VEGF agents may be different during the induction phase for eyes with occult CNV secondary to neovascular AMD. Keywords: neovascular age-related macular degeneration, occult, ranibizumab, aflibercept, retinal thickness, outer nuclear layer

PURPOSE. We evaluated retrospectively the morphologic choroidal and scleral characteristics in eyes with pathologic myopia using high-penetration optical coherence tomography (HP-OCT) or swept-source OCT (SS-OCT). METHODS. The subfoveal choroidal and scleral thicknesses were measured using the prototype HP-OCT with a 1060 nm light source. We also measured the scleral thickness 3 mm superior, inferior, nasal, and temporal to the fovea on the horizontal and vertical OCT sections. The axial length (AL) in all eyes was measured using optical biometry. RESULTS. We examined 58 eyes of 35 patients (7 men and 28 women, mean age 65.5 years) with an AL exceeding 26.5 mm. The mean AL was 29.0 6 1.4 mm. The full-thickness choroid and sclera were visualized in all eyes. The mean subfoveal choroidal and scleral thicknesses were 52 6 38 and 335 6 130 lm, respectively. The mean scleral thicknesses 3 mm superior, inferior, nasal, and temporal to the fovea were 266 6 78 (n ¼ 57), 259 6 72 (n ¼ 56), 324 6 109 (n ¼ 39), and 253 6 79 (n ¼ 58) lm, respectively. The subfoveal sclera was thicker than 3 mm outside the fovea (P < 0.05, for each comparison). CONCLUSIONS. The full-thickness choroid and sclera in all eyes with pathologic myopia were visualized using a prototype HPOCT. The subfoveal sclera was thicker than 3 mm outside the fovea. HP-OCT is a useful tool for morphologic analyses of pathologic myopia. (Invest Ophthalmol Vis Sci. 2012;53:3834– 3838) DOI:10.1167/iovs.12-9811

To evaluate the morphologic retinal and choroidal changes after verteporfin photodynamic therapy (PDT) with and without ranibizumab for polypoidal choroidal vasculopathy using spectral-domain optical coherence tomography.Retrospective, comparative series.The enhanced depth imaging optical coherence tomography technique was used in this retrospective, comparative series to measure the subfoveal retinal and choroidal thicknesses before and after treatment.Twenty-seven eyes with polypoidal choroidal vasculopathy were examined retrospectively. Sixteen eyes were treated with PDT monotherapy (PDT group). Eleven eyes were treated with PDT after intravitreal ranibizumab injection (ranibizumab plus PDT group). The polypoidal lesions regressed in all cases at 3 months. The mean retinal thickness, including the retinal detachment, increased from 401 ± 157 μm before treatment to 506 ± 182 μm 2 days after PDT (P.001) and decreased to 365 ± 116 μm by 1 week after treatment (P=.03) and 265 ± 127 μm by 6 months after treatment (P.001). The mean choroidal thickness increased from 269 ± 107 μm before treatment to 336 ± 96 μm 2 days after PDT treatment (P.001 compared with baseline) and decreased to 262 ± 96 μm by 1 week after treatment (P=.24) and 229 ± 104 μm by 6 months (P.001). Although the choroidal thickness showed a similar trend with both therapies, the retinal thickness in the ranibizumab plus PDT group remained thinner than that in the PDT group until 6 months after treatment.PDT was associated with decreased retinal and choroidal thicknesses. Combination therapy reduced the transient exudation after PDT in some cases, and monthly intravitreal ranibizumab injections maintained retinal thinning and seemed to improve vision better than PDT monotherapy.