Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa.

Transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into retinal disease animal models has yielded promising results, and several clinical trials on iPSC-derived retinal pigment epithelial cell transplantation have confirmed its safety. In this study, we performed allogeneic iPSC-derived retinal organoid sheet transplantation in two subjects with advanced retinitis pigmentosa (jRCTa050200027). The primary endpoint was the survival and safety of the transplanted retinal organoid sheets in the first year post-transplantation. The secondary endpoints were the safety of the transplantation procedure and visual function evaluation. The grafts survived in a stable condition for 2 years, and the retinal thickness increased at the transplant site without serious adverse events in both subjects. Changes in visual function were less progressive than those of the untreated eye during the follow-up. Allogeneic iPSC-derived retinal organoid sheet transplantation is a potential therapeutic approach, and the treatment's safety and efficacy for visual function should be investigated further.

Ten-year outcomes of cataract surgery for glaucoma management in patients with primary angle-closure disease.

PURPOSE: To investigate the long-term outcomes of cataract surgery for glaucoma management in patients with primary angle-closure disease (PACD). STUDY DESIGN: Retrospective case series. METHODS: We reviewed the medical records of 87 eyes of 87 patients with PACD who underwent uncomplicated cataract surgery alone at the Kobe City Medical Center General Hospital. Only patients with a minimum follow-up of 10 years were included. The patients were divided into PACD spectrum categories: primary angle-closure glaucoma (PACG), primary-angle closure (PAC), and primary angle-closure suspect (PACS). The treatment outcomes were compared among the 3 groups. Intraocular pressure (IOP), number of glaucoma eye drops, requirement of additional glaucoma treatment, visual field progression, and progression to glaucoma during the follow-up period were evaluated. RESULTS: Among the 87 patients, 39 had PACG; 26, PAC; and 22, PACS. Ten years after surgery, the IOP had significantly decreased from baseline in all 3 groups. The rate of requirement of additional glaucoma treatment during the follow-up period was significantly higher in the PACG group than in the other groups. Almost half of the patients with PACG required additional glaucoma treatment; of those patients, six (15.4%) underwent glaucoma surgery. Three patients (11.5%) with PAC required additional glaucoma medication. Visual field progression was observed in 28.1% of the patients with PACG. In 1 patient with PAC, the condition progressed to PACG, but there was no such progression in any of the patients with PACS. CONCLUSIONS: We confirmed that cataract surgery had a long-term (> 10 years) effect on IOP reduction in eyes with PACD. Early intervention with cataract surgery may be preferable for glaucoma management in patients with PACD.

One-year outcomes and predictable factors for microhook ab interno trabeculotomy.

AIM: To investigate the one-year outcomes and factors that influence the results of microhook ab interno trabeculotomy (µLOT). METHODS: The medical records of consecutive patients with open angle glaucoma who underwent µLOT (including combination of µLOT and cataract surgery) between February 2018 and July 2019 were retrospectively reviewed. Surgical success was defined as the following: an intraocular pressure (IOP)≤21 mm Hg or IOP≤preoperative IOP with a reduced number of glaucoma eye drops, without additional glaucoma surgery, and assessed using Kaplan-Meier survival analysis. A multivariate Cox proportional-hazards regression model was used to investigate the factors associated with surgical failure. RESULTS: The 59 eyes of 59 patients comprising 28 eyes with primary open angle glaucoma (POAG) and 31 with secondary open angle glaucoma (SOAG) were included. The mean IOP and number of glaucoma eye drops significantly decreased from 25.3±7.2 mm Hg and 3.9±1.1, preoperatively to 16.1±4.4 mm Hg (P<0.01) and 2.1±1.8 (P<0.01), respectively, 12mo postoperatively, with a cumulative success rate of 63.1%. The one-year success rate was significantly higher in POAG eyes than in SOAG eyes (80.0% vs 48.0%; P=0.011, log-rank test). Multivariate analyses revealed SOAG [P=0.017, adjusted hazard ratio (aHR): 3.468, 95%CI: 1.246-9.654] and the postoperative IOP spike (IOP>25 mm Hg within 2wk post-surgery; P<0.001, aHR: 5.382, 95%CI: 2.113-13.707) as independent factors associated with surgical failure. CONCLUSION: The µLOT is a good treatment option for POAG eyes. However, the postoperative course should be carefully followed in cases with postoperative IOP spike.

Evaluation of Transplanted Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in Exudative Age-Related Macular Degeneration.

PURPOSE: To report the results after 4 years of follow-up in a previously presented first case of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet autologous transplantation using multimodal imaging. DESIGN: Follow-up of a single case. PARTICIPANT: A patient with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: Transplantation of an autologous iPSC-derived RPE cell sheet after removal of choroidal neovascularization (CNV) in September 2014. MAIN OUTCOME MEASURES: The function of the graft was assessed 4 years after surgery by color fundus photography, spectral-domain (SD) OCT, fluorescein angiography, indocyanine green angiography, and an adaptive optics (AO) retinal camera. RESULTS: At the 4-year follow-up, the transplanted autologous iPSC-derived RPE sheet had survived beneath the retina with slight expansion of the pigmented area and no adverse events. The outer nuclear layer above and adjacent to the graft showed acceptable thickness and an organized structure. Fluorescein angiography and SD OCT suggested the presence of vessel-like structures confined to the grafted area associated with the remaining trunk vessel of preoperative polypoidal choroidal vasculopathy but with no exudative changes. Visual acuity has been stable with no additional injections of anti-vascular endothelial growth factor agent. The choroidal volume at the graft site is relatively preserved when compared with the volume outside this site without RPE after removal of the CNV. Indocyanine green angiography revealed a preserved choriocapillaris around the iPSC-derived RPE sheet. Dark cell-like structures with a predominantly hexagonal arrangement were observed by AO imaging in an area located near the margin of the graft sheet. The average intercell distance was found to be stable over time. CONCLUSIONS: Thus far, the grafted iPSC-derived RPE sheet has survived for 4 years and seems to support photoreceptors and choroidal vessels. The morphologic characteristics of the RPE are observed at the transplant site.

A case of bilateral vasculitis associated with pineal germinoma.

PURPOSE: To report a rare case of bilateral periphlebitis associated with a pineal germinoma. OBSERVATIONS: A 17-year-old male teenager presented at a local clinic complaining of blurred vision in both eyes. The treating physician identified bilateral uveitis, and prescribed the patient with a local steroid treatment. However, the inflammatory findings did not improve with the treatment, and the patient was referred to our hospital for further examination. At the first visit, his best-corrected visual acuities were 0.3 for the right eye and 0.06 for the left eye; we found no inflammation in the anterior ocular segment, but observed bilateral retinal periphlebitis and a proliferative membrane from the papilla to the macula in the ocular fundus. In addition, we found a tractional serous retinal detachment in the macula. We suspected tuberculous uveitis clinically and initiated treatment with an antituberculous drug. However, the condition of the patient did not improve. Two months after our initial examination, left optic neuritis appeared, and we initiated a steroid pulse therapy. Although the periphlebitis remained, the left optic nerve findings and the visual acuity of both eyes improved. Thus, we reduced the oral steroid dose gradually. However, two months after initiating the dose reduction, the patient suffered a consciousness disturbance, and we detected a pineal tumor by magnetic resonance imaging (MRI). The patient was diagnosed as having a germ cell tumor by pathological examination and underwent radiation and chemotherapy. We noted marked improvements in both the periphlebitis findings and in the visual acuity following the treatment for the pineal tumor. CONCLUSIONS AND IMPORTANCE: Cases of pineal tumor accompanied with retinal periphlebitis have been reported rarely. Because juvenile retinal vasculitis cases of unknown cause can be associated with pineal germinomas, we recommend brain MRI examinations for such cases.

Efficacy of additional topical betamethasone in persistent cystoid macular oedema after carbonic anhydrase inhibitor treatments in retinitis pigmentosa.

OBJECTIVE: We investigated the efficacy of additional topical betamethasone in persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors (CAIs) therapy. METHODS AND ANALYSIS: This retrospective cohort study included 16 eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously administered CAI for at least 3 months to treat CMO secondary to RP and lacking an effective reduction (≥11%) of central foveal thickness (CFT). We administered topical 0.1% betamethasone daily in each affected eye following a preceding course of the CAI medication as a first treatment. CMO was diagnosed using spectral-domain optical coherence tomography. CFT was regarded as the average of vertical and horizontal foveal thickness. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained from patient medical records. We compared the CFT and BCVA between baseline and the average of 1-3, 5-7, 10-14 and 16-20 months period. RESULTS: In treatments with brinzolamide in 14 eyes, dorzolamide in 2 eyes and bromfenac in 2 eyes, CFT effectively decreased in 12 of 16 eyes (81%). CFT decreased significantly in 1-3 months (326±102 µm; n=16; P=0.029) and 5-7 months (297±102 µm; n=12; P=0.022) compared with baseline but not within 10-14 months (271±96 µm; n=9; P=0.485) or 16-20 months (281±134 µm; n=9; P=0.289). There were no significant intergroup differences in BCVA throughout the study. Betamethasone treatment was stopped in three patients because of IOP elevation. CONCLUSION: Our data suggested that additional betamethasone might improve treatments for persistent CMO. Topical steroids could be an alternative option for managing persistent CMO in RP.

Unique circumferential peripheral keratitis in relapsing polychondritis: A case report.

RATIONALE: Relapsing polychondritis (RP) is a rare collagen disease characterized by inflammation and destruction of cartilage throughout the body. The paper details the clinical course of a case of RP with unique circumferential peripheral keratitis. PATIENT CONCERNS: A 54-year-old Japanese woman was referred to the hospital presenting with auricular and ocular pain. DIAGNOSES: Based on the auricle biopsy results and the three presenting symptoms (bilateral auricular chondritis, inflammatory arthritis and ocular inflammation), her condition was diagnosed as RP. INTERVENTIONS: The three presenting symptoms gradually improved with prednisolone (PSL), methylprednisolone and cyclophosphamide combination therapy, followed by PSL, methotrexate and infliximab combination therapy. However, one month after the initial visit, despite ongoing treatment, a unique circumferential peripheral keratitis suddenly occurred, in which the corneal infiltration gradually clumped together and shrank at the peripheral area. The eye and ear pain showed exacerbations and remissions on reducing the dosage of steroid drugs. The general condition was improved on altering systemic therapy to PSL, methotrexate and tocilizumab. OUTCOMES: Keratitis gradually disappeared within 10 months of the initial visit. LESSONS: This is the first report of a case of RP causing unique circumferential peripheral keratitis. This keratitis occurred despite use of focal and systemic steroids and showed improvement with general recovery. This may indicate that stabilization of general condition is important for recovery from keratitis in RP.

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal vasculopathy: 12-month LAPTOP study results.

PURPOSE: To compare the effect of photodynamic therapy (PDT) and intravitreal ranibizumab in patients with polypoidal choroidal vasculopathy (PCV). DESIGN: Randomized clinical trial. SETTING: Multicenter. STUDY POPULATION: Total of 93 patients with treatment-naïve PCV. INTERVENTION: Patients were randomized to 2 arms. Patients in the PDT arm underwent a single session of PDT with verteporfin, and patients in the ranibizumab arm received 3 monthly ranibizumab injections at baseline. Additional treatment was performed as needed in each arm. MAIN OUTCOME MEASURES: Primary outcome measurement was the proportion of patients gaining or losing more than 0.2 logarithm of minimal angle of resolution (logMAR) units from baseline. Mean change of logMAR and central retinal thickness (CRT) were also evaluated. RESULTS: In the PDT arm (n = 47), 17.0% achieved visual acuity gain, 55.3% had no change, and 27.7% experienced visual acuity loss. The results were 30.4%, 60.9%, and 8.7%, respectively, in the ranibizumab arm (n = 46), significantly better than the PDT arm (P = .039). In the PDT arm, mean CRT improved (366.8 ± 113.6 µm to 289.1 ± 202.3 µm, P < .001), but logMAR was unchanged (0.57 ± 0.31 to 0.62 ± 0.40). The ranibizumab arm demonstrated improvement in both CRT (418.9 ± 168.6 µm to 311.2 ± 146.9 µm, P < .001) and logMAR (0.48 ± 0.27 to 0.39 ± 0.26, P = .003). Mean change of logMAR was also greater in the ranibizumab arm (P = .011). CONCLUSION: Intravitreal injection of ranibizumab is more effective than PDT for treatment-naïve PCV.

Visual outcome of photodynamic therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy over 5 years of follow-up.

PURPOSE: To evaluate the long-term effects of photodynamic therapy (PDT) on typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This was a multicenter prospective study of 139 eyes from 136 patients (tAMD: 74 eyes; PCV: 65 eyes) who underwent PDT as the initial treatment. The change in best-corrected visual acuity (BCVA), predictive factors for the BCVA at 60 months, frequency of recurrence, and mean recurrence period were analyzed. RESULTS: The pre-PDT BCVA and greatest linear dimension (GLD) did not differ between the two groups. The mean BCVA (logMAR) was significantly improved at 6 months post-initial PDT (post-PDT) in the PCV group (-0.11, P = 0.0091). However, at 60 months post-PDT, the mean BCVA was significantly worse than baseline in the tAMD (+0.21, P = 0.0035) and PCV (+0.21, P = 0.0076) groups. Pre-PDT BCVA, age, and GLD were the factors significantly associated with the BCVA at 60 months post-PDT. Although the frequency of recurrence did not significantly differ between the two phenotype groups, the mean recurrence period was significantly longer in the PCV group than in the tAMD group (15.7 vs. 8.6 months, P = 0.0020). CONCLUSIONS: PDT may not have benefits for visual acuity in cases of tAMD and PCV over 5 years of follow-up.

Cigarette smoking, oxidative stress, the anti-oxidant response through Nrf2 signaling, and Age-related Macular Degeneration.

Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. Cigarette smoking is the strongest epidemiologic risk factor, yet we do not understand how smoking contributes to AMD. Smoking related oxidative damage during the early phases of AMD may play an important role. This review explores how cigarette smoking and oxidative stress to the retinal pigmented epithelium (RPE) might contribute to AMD, and how the transcription factor Nrf2 can activate a cytoprotective response.

Nrf2 is a critical modulator of the innate immune response in a model of uveitis.

Uveitis is an inflammatory condition that can lead to blindness. It is therefore important to understand the pathophysiology against which to develop targeted therapy. Herein, we tested whether the oxidant-responsive transcription factor Nrf2 is involved in regulating the innate immune response and oxidative damage in the LPS uveitis model. As shown by dihydroethidium staining, intraperitoneally injected LPS increased reactive oxygen species in the retina and iris-ciliary body of Nrf2+/+ and Nrf2-/- mice. After LPS injection, ICAM-1, IL-6, TNF-alpha, COX-2, iNOS, and MCP-1 mRNAs were increased more in the retina and iris-ciliary body of Nrf2-/- than in those of Nrf2+/+ mice. NQO-1 and GCLM, two Nrf2-responsive antioxidant enzymes, had reduced expression in Nrf2+/+ retinas after LPS injection, but no change in expression in Nrf2-/- mice. The number of FITC-Con A-labeled leukocytes adherent to the retinal vascular endothelium increased after LPS treatment in both Nrf2+/+ and Nrf2-/- mice compared to control injections, with more adherent leukocytes in Nrf2-/- than in Nrf2+/+ mice. Pretreatment with the Nrf2 activator 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)imidazole increased antioxidant gene expression in the retina, reduced inflammatory mediator expression, and reduced leukocyte adherence to retinal vasculature after LPS treatment in Nrf2+/+ mice, but had no effect on Nrf2-/- mice. Treatment targeting the Nrf2 pathway may be a new therapy for uveitis.

Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice.

The purpose of this study was to determine whether mice exposed to chronic cigarette smoke develop features of early age-related macular degeneration (AMD). Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in 2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes by transmission electron microscopy. The contralateral eye was fixed in 2% paraformaldehyde and examined for oxidative injury to the retinal pigmented epithelium (RPE) by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) immunolabeling and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had immunolabeling for 8-OHdG in 85+/-3.7% of RPE cells counted compared to 9.5+/-3.9% in controls (p<0.00001). Bruch membrane was thicker in mice exposed to smoke (1086+/-332 nm) than those raised in air (543+/-132 nm; p = 0.0069). The two most pronounced ultrastructural changes (severity grading scale from 0-3) seen were a loss of basal infoldings (mean difference in grade = 1.98; p<0.0001), and an increase in intracellular vacuoles (mean difference in grade = 1.7; p<0.0001). Ultrastructural changes to Bruch membrane in cigarette-smoke exposed mice were smaller in magnitude but consistently demonstrated significantly higher grade injury in cigarette-exposed mice, including basal laminar deposits (mean difference in grade = 0.54; p<0.0001), increased outer collagenous layer deposits (mean difference in grade = 0.59; p = 0.002), and increased basal laminar deposit continuity (mean difference in grade = 0.4; p<0.0001). TUNEL assay showed a higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 8.0+/-1.1%) than room air (average 0+/-0%; p = 0.043). Mice exposed to chronic cigarette smoke develop evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model could be useful for studying the mechanism of smoke induced changes during early AMD.

Angle widening and alteration of ciliary process configuration after cataract surgery for primary angle closure.

PURPOSE: To evaluate quantitatively, by means of ultrasound biomicroscopy (UBM), changes in the anterior segment configuration, including the ciliary processes, induced by cataract surgery in eyes with primary angle closure. DESIGN: Retrospective interventional case series. PARTICIPANTS: Thirty-one eyes of 31 patients with primary angle closure or primary angle-closure glaucoma were treated with cataract surgery. Before cataract surgery, 10 eyes had been treated with laser peripheral iridotomy, and 1 with laser peripheral iridoplasty. METHODS: Configuration of the anterior chamber was examined by means of UBM before and at 3 months after cataract surgery. MAIN OUTCOME MEASURES: Using UBM, anterior chamber depth (ACD), angle opening distance at points 500 mum from the scleral spur (AOD500), and trabecular-ciliary process distance (TCPD) were measured. RESULTS: Not only ACD and AOD500, but also TCPD, increased significantly after cataract surgery, compared with measurements obtained before surgery (P<0.001). Postoperative AOD500 was correlated significantly with postoperative TCPD (r = 0.72, P<0.001) and with the amount of change of TCPD caused by cataract surgery (Delta TCPD) (r = 0.52, P<0.01). CONCLUSIONS: Cataract surgery attenuated anterior positioning of the ciliary processes in eyes with primary angle closure, concomitant with significant widening of the angle. Cataract surgery resulted in not only complete dissolution of lens volume and pupillary block, but also attenuation of the anterior positioning of the ciliary processes, all of which contributed to postoperative widening of the angle in eyes with primary angle closure.

Triamcinolone acetonide with vitrectomy for treatment of macular edema associated with branch retinal vein occlusion.

PURPOSE: To review the efficacy of a combination of triamcinolone acetonide (TA) injection and pars plana vitrectomy (PPV) for the treatment of macular edema associated with branch retinal vein occlusion (BRVO). METHODS: Seventeen eyes with macular edema associated with BRVO underwent PPV with an intraoperative injection of TA (10 mg) into the vitreous cavity. Residual or recurrent macular edema was treated with postoperative sub-Tenon capsule injections of TA (20 mg). RESULTS: With PPV and an intraoperative injection of TA, 82% of eyes showed rapid reduction of macular edema; foveal thickness decreased from 507 +/- 115 microm preoperatively to 261 +/- 123 microm 2 months after surgery (P = 0.0041). However, 59% of eyes showed recurrence of macular edema during the follow-up period. Twelve eyes with residual or recurrent macular edema received sub-Tenon capsule injections of TA; of these eyes, 9 showed substantial reduction of macular edema. Foveal thickness decreased from 381 +/- 102 microm to 256 +/- 56 microm (P = 0.0076) 2 weeks after postoperative injections of TA. At the final visit, visual acuity (logMAR) improved from 0.74 +/- 0.40 preoperatively to 0.40 +/- 0.34 (P = 0.010). CONCLUSION: An intraoperative injection of TA in combination with PPV has the potential to facilitate the absorption of macular edema associated with BRVO. In addition, residual or recurrent macular edema can be treated with additional sub-Tenon capsule injections of TA.

Cataract surgery for residual angle closure after peripheral laser iridotomy.

PURPOSE: To investigate the frequency of residual angle closure after resolution of pupillary blocking by laser peripheral iridotomy and the effects of subsequent cataract surgery to resolve angle closure completely. DESIGN: Retrospective, consecutive, interventional study. PARTICIPANTS: Among 70 eyes treated with laser iridotomy, 13 with residual angle closure were treated with cataract surgery. METHODS: The provocative test of angle closure by prone position in a dark room for 1 hour was performed; increases in tension of > or =8 mmHg, 6 or 7 mmHg, and < or =5 mmHg were considered to be positive, suspected positive, and negative, respectively. Configuration of the anterior chamber was examined using ultrasound biomicroscopy (UBM). MAIN OUTCOME MEASURES: Intraocular pressure (IOP), response to the dark room prone position test, and morphologic analysis by UBM were evaluated before and 3 months after cataract surgery. RESULTS: Residual angle closure after iridotomy was seen in 27 (38.6%) of 70 eyes; this was confirmed functionally by the dark room prone position test and morphologically by UBM. Eyes with IOP of > or =20 mmHg or with a glaucomatous visual field defect before iridotomy had a significantly higher incidence of residual angle closure after iridotomy than eyes without these findings (P<0.05). In all the eyes with residual angle closure after iridotomy, the response to the prone position test became negative after cataract surgery, with significant lowering of IOP (P<0.01). CONCLUSIONS: Residual angle closure after iridotomy was common, especially in eyes with primary angle closure and poorly controlled IOP or glaucomatous optic neuropathy. Cataract surgery was effective to resolve completely the residual angle closure after iridotomy and lower IOP.

Retinal cystoid spaces in acute Vogt-Koyanagi-Harada syndrome.

PURPOSE: Exudative retinal detachment in acute Vogt-Koyanagi-Harada syndrome often is associated with subfoveal yellowish round structures. This report describes the incidence and clinical characteristics of these structures. DESIGN: Interventional case series. METHODS: We reviewed the fundus photographs and medical records of 35 eyes of 19 Japanese patients with bilateral diffuse choroiditis at the onset of acute Vogt-Koyanagi-Harada syndrome. RESULTS: All eyes showed subretinal fluid in the posterior pole. In addition, yellowish round structures were seen in 15 eyes (43%). Most of the yellowish structures were subfoveal in location and ranged in size from less than 1 disk diameter to 3 disk diameters. In 6 eyes with these structures, optical coherence tomography showed liquid accumulation in the retina or thin walls, which seemed to separate the cystoid spaces from the subretinal fluid. Late-phase fluorescein angiography showed pooling of dye within these structures as well as within the subretinal fluid. Immediately after corticosteroid administration was initiated, these structures began to be less obvious, and they disappeared completely within several days; there was a concomitant reduction in the subretinal fluid. At the initial visit, visual acuity in eyes with these yellowish structures was slightly less than that in eyes without them, but no differences in visual acuity were found during the period of follow-up. CONCLUSION: Subfoveal yellowish round structures may be a common feature in acute Vogt-Koyanagi-Harada syndrome. However, they appear to have only a minor (if any) effect on visual prognosis.