T cell immunoregulation in active ocular toxoplasmosis.

Toxoplasma gondii infection is an important cause of infectious ocular disease. The physiopathology of retinochoroidal lesions associated with this infection is not completely understood. The present study was undertaken to investigate cytokine production by T cells from individuals with active toxoplasmic retinochoroiditis (TR) comparing with controls. Eighteen patients with active TR and 15 healthy controls (6 controls IgG+ to Toxoplasma and 9 negative controls) were included in the study. Peripheral blood mononuclear cells were incubated in the presence or absence of T. gondii antigen (STAg), and stained against CD4, CD8, TNF, IL-10 and IFN-γ. Baseline expression of cytokines was higher in TR/IgG+ patients in comparison with controls. Cytokine expression was not increased by STAg in vitro stimulation in controls. After stimulation, TR/IgG+ patients' lymphocytes increased cytokine as compared to cultures from both controls. While T cells were the main source of IL-10, but also IFN-γ and TNF, other lymphocyte populations were relevant source of inflammatory cytokines. Interestingly, it was observed a negative correlation between ocular lesion size and IL-10 expression by CD4+ lymphocytes. This study showed that T cells are the main lymphocyte populations expressing IL-10 in patients with TR. Moreover, expression of IL-10 plays a protective role in active TR.

Multimodal Imaging Assisting the Early Diagnosis of Cat-Scratch Neuroretinitis.

To describe how a multifocal fundus imaging system assisted the early diagnosis of cat scratch neuroretinitis in a case of a 27-year-old male with unilateral visual loss, neuroretinitis, and a peripapillary angiomatous lesion. Multimodal fundus imaging analysis was an essential contributor to the clinical diagnosis of cat scratch neuroretinitis during the early stage of the disease.

High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids.

PURPOSE: To analyse the rate of clinical recurrences in Brazilian patients with Vogt-Koyanagi-Harada (VKH) disease after early high-dose corticosteroid treatment. METHODS: Retrospective study including patients treated with early high-dose corticosteroids (prednisone, 1-1.5 mg/kg/day, or 3-day 1 g methylprednisolone pulsetherapy) within 1 month from disease onset followed by slow taper (at least 6 months). Patients with a minimum 12-month follow-up were subdivided based on the presence of disease recurrence or persistence after 6 months from initial presentation into: acute-resolved (AR, no recurrences), chronic-recurrent (CR), and chronic-recurrent with subretinal fibrosis (SRF). Recurrences were defined as the presence of clinical and/or fluorescein angiography findings. RESULTS: Twenty-nine patients (58 eyes) with a median follow-up of 65 months were included. Six (21 %), 11 (38 %) and 12 (41 %) patients were allocated to AR, CR, and SRF groups respectively. Though having received treatment within 1 month of onset, median time to initial treatment differed among groups (11, 15, and 25 days, in AR, CR, and SRF groups respectively). Intensity of immunosuppression, cataract development, and longer time to achieve logMAR visual acuity ≤0.8 differed significantly among the groups, being more severe in SRF group. HLA-DRB1*0405 allele followed the same trend, though not reaching significance (0.5 in AR group, 0.6 in CR, and 0.8 in SRF). CONCLUSION: VKH disease in Brazilian patients evolved to chronic-recurrent disease in 79 % of cases; 38 % developed subretinal fibrosis, in spite of similar initial treatment regimens. Time to initiate treatment influenced outcomes.

Multilayered pigment epithelial detachment in neovascular age-related macular degeneration.

PURPOSE: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. RESULTS: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. CONCLUSION: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a "pre-choroidal cleft," separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium.

Choroidal bulging in patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage.

BACKGROUND: Detection of choroidal inflammation in Vogt-Koyanagi-Harada (VKH) disease is still a challenge. Progression to sunset glow fundus has been observed despite apparent good clinical control of inflammation. Indocyanine green angiography (ICGA) permits choroid inflammation detection, though it is invasive, time consuming, and costly. The purpose of the present study is to report a sign indicative of probable inflammation on enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT): a localized increase in choroidal thickness with bulging of the outer retina ('choroidal bulging') in patients with VKH disease in the non-acute uveitic stage. FINDINGS: This is a retrospective observational study. The choroidal bulging was a particular finding observed in four eyes of three patients with VKH disease in the non-acute uveitic stage (median disease duration 55.3 ± 40.3 months, range 10 to 108). This study is part of an ongoing longitudinal study in patients with VKH disease carried out in the Uveitis Service, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. In all eyes, the choroidal bulging was identified in the presence of anterior chamber cells and/or on fundus angiographic (fluorescein and indocyanine green) findings, indicative of disease activity. Changes in the thickness of the choroidal bulging accompanied the variation in the clinical and angiographic signs of inflammation. CONCLUSION: The choroidal bulging is a particular finding detected on EDI-OCT that may indicate ongoing inflammation in the posterior segment of the eye. This EDI-OCT feature may assist in the treatment-monitoring of patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage.

Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study): 1-year results.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on area of fluorescein leakage from active new vessels (NVs) and on best-corrected visual acuity in patients with actively leaking NV associated with diabetic retinopathy unresponsive to panretinal photocoagulation. METHODS: A prospective open-label study of diabetic patients with actively leaking NV refractory to panretinal photocoagulation and best-corrected visual acuity worse than 20/40. Ophthalmic evaluation, including fluorescein angiography, was performed at baseline and at Weeks 1, 6, 12, 24, and 48 after intravitreal bevacizumab (1.5 mg/0.06 mL) injection. After Week 12, patients could receive additional intravitreal bevacizumab injections pro re nata, per the discretion of the treating ophthalmologist. Main outcome measures include change from baseline (at each study visit) in total area of fluorescein leakage from active NV and change from baseline in best-corrected visual acuity. RESULTS: Fifteen consecutive patients were included, and 12 completed the study. Mean ± SEM fluorescein leakage was 27.7 ± 6.2 mm at baseline and was significantly lower at all visits post injection; at Week 6, no leakage was observed (P = 0.0001). The mean ± SEM logarithm of minimum angle of resolution best-corrected visual acuity improved from 0.90 ± 0.11 at baseline to 0.70 ± 0.12 at Week 48 (P = 0.0449). Throughout the 48-week study period, patients received a mean of 2.16 injections. CONCLUSION: With 1-year follow-up, treatment with intravitreal bevacizumab was associated with reduced fluorescein leakage from persistent NV and improved visual acuity in patients with diabetic retinopathy unresponsive to panretinal photocoagulation.

Influence of the eye-tracking-based follow-up function in retinal nerve fiber layer thickness using fourier-domain optical coherence tomography.

PURPOSE: To evaluate the eye-tracking-based follow-up (EBF) function in the reproducibility of the peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained with Fourier-domain optical coherence tomography (Fd-OCT). METHODS: Thirty healthy subjects were imaged on an Fd-OCT device at the same visit by two examiners. Peripapillary circular scans in "high-speed" (HS) mode with the "automatic real time" (ART) set at 16 and in "high-resolution" (HR) mode with the ART off were obtained without and with the EBF function activated. RESULTS: Mean (± SD) global RNFL thickness was 105.1 (± 9.5) µm on HS mode and 105.4 (± 9.6) µm on HR mode. Interobserver analysis for global RNFL thickness revealed an intraclass correlation coefficient (ICC) greater than or equal to 0.96 for all but the HR mode without the use of EBF function (ICC = 0.73). Intraobserver analysis for global RNFL thickness revealed an ICC greater than 0.98 for all but the HR mode without the use of EBF function (ICC = 0.86). The interobserver and intraobserver analyses revealed the lowest ICC values for the temporal region on both HS and HR modes. Higher ICC values were obtained with the HS mode and when the EBF function was activated, particularly when using the HR mode. CONCLUSIONS: The EBF function had no influence in the reproducibility of the global peripapillary RNFL thickness measurements in healthy subjects on HS mode with ART on. However, reproducibility of the global RNFL thickness measurements on HR mode as well as of the temporal and temporal superior regions in both HS and HR modes was greater with the EBF function.

Spectral optical coherence tomography findings in patients with ocular toxoplasmosis and active satellite lesions (MINAS Report 1).

PURPOSE: To characterize the active retinochoroiditis lesion observed in patients with the classic clinical presentation of ocular toxoplasmosis (OT) utilizing spectral optical coherence tomography (SOCT). METHODS: Twenty-four patients with OT and satellite lesions underwent standardized ophthalmologic examination and multimodal fundus imaging. The SOCT findings observed at presentation were described. RESULTS: The mean age of the fourteen (58.3%) women and ten (41.7%) men was 27.6 years. The mean LogMAR ETDRS best-corrected visual acuity was 0.58 (Snellen equivalent, 20/80(+1) ). On SOCT evaluation, the posterior hyaloid was diffusely thickened in 23 (95.8%) of 24 eyes, increased hyper-reflective signals in the vitreous were observed in 18 (75.0%), and vitreal spherical hyper-reflective depositions were observed in 12 (50.0%) eyes. In all patients, at the active OT lesion site, the inner retinal layers were abnormally hyper-reflective with full-thickness disorganization of the retinal reflective layers (smudge effect); associated choriocapillaris/choroidal optical shadowing was observed in 22 (91.7%) eyes. The retina was thickened in 22 (91.7%) eyes, the retinal pigment epithelium-Bruch membrane reflective complex was focally increased or contained focal splits in 16 (66.7%) eyes and the choroid appeared thickened in 17 (70.8%) eyes. Disorganization of the outer retinal highly reflective layers adjacent to the active OT lesion was observed in all eyes. CONCLUSION: Full-thickness disorganization of the retinal reflective layers, generally associated with some degree of posterior optical shadowing, was observed in the active OT lesion in all patients. The posterior hyaloid was often thickened and, adjacent to the OT lesion, the outer retina was consistently altered.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study.

BACKGROUND: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. METHODS: Twenty-eight patients (51 eyes) with long-standing (≥6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. RESULTS: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). CONCLUSION: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Optical coherence tomographic imaging of sub-retinal pigment epithelium lipid.

OBJECTIVE To describe an optical coherence tomographic finding of layered hyperreflective bands beneath the retinal pigment epithelium (RPE), the so-called onion sign believed to represent lipid within a vascularized pigment epithelial detachment. METHODS This retrospective observational case series involved reviewing clinical histories of patients with the onion sign. Imaging studies analyzed included spectral-domain optical coherence tomography, color and red-free photographs, near infrared reflectance, fundus autofluorescence, and blue-light fundus autofluorescence. RESULTS A total of 22 eyes of 20 patients with sub-RPE hyperreflective bands were identified. There were 15 women and 5 men with a mean patient age of 76 years (range, 60-92 years). Snellen best-corrected visual acuities ranged from 20/25 to counting fingers, with a median of 20/80. Two patients had bilateral involvement, and 3 of 17 eyes had multifocal onion signs in the same eye. All eyes had neovascular age-related macular degeneration, with type 1 (sub-RPE) neovascularization. In all patients, the onion sign correlated with areas of yellow-gray exudates seen clinically that appeared bright on red-free and near infrared reflectance imaging. No specific fundus autofluorescence or blue-light fundus autofluorescence pattern was identified. CONCLUSIONS The onion sign refers to layered hyperreflective bands in the sub-RPE space usually associated with chronic exudation from type 1 neovascularization in patients with age-related macular degeneration. With an associated bright near infrared reflectance, these bands may correspond to lipid, collagen, or fibrin. Because the onion sign colocalizes to areas of exudation that are known to consist of lipoprotein, we propose that this finding may represent layers of precipitated lipid in the sub-RPE space. To our knowledge, this is the first report of lipid detected in the sub-RPE space on clinical examination.

Electroretinographic findings associated with panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab treatment for high-risk proliferative diabetic retinopathy.

To evaluate changes in electroretinographic (ERG) findings after panretinal photocoagulation (PRP) compared to PRP plus intravitreal injection of ranibizumab (IVR) in eyes with high-risk proliferative diabetic retinopathy (PDR). Patients with high-risk PDR and no prior laser treatment were assigned randomly to receive PRP (PRP group; n = 9) or PRP plus IVR (PRPplus group; n = 11). PRP was administered in two sessions (weeks 0 and 2), and IVR was administered at the end of the first laser session (week 0) in the PRPplus group. Standardized ophthalmic evaluations including (ETDRS) best-corrected visual acuity (BCVA), and fluorescein angiography to measure area of fluorescein leakage (FLA), were performed at baseline and at weeks 16 (±2), 32 (±2) and 48 (±2). ERG was measured according to ISCEV standards at baseline and at week 48 (±2). At 48 weeks, 2,400-3,000 laser spots had been placed in eyes in the PRP group, while only 1,400-1,800 spots had been placed in the PRPplus group. Compared to baseline, there was a statistically significant (P < 0.05) FLA reduction observed at all study visits in both groups, with the reduction observed in the PRPplus group significantly larger than that in the PRP group at week 48. ROD b-wave amplitude was significantly reduced to 46 ± 5% (P < 0.05) of baseline in the PRP group and 64 ± 6% (P < 0.05) in the PRPplus group. This reduction was significantly larger in the PRP group than in the PRPplus group (P = 0.024; t Test). Similar results were observed for the dark-adapted Combined Response (CR) b-wave amplitude, with a reduction at 48 weeks compared to baseline of 45 ± 4% in the PRP group and 62 ± 5% in the PRPplus group; the reduction in CR b-wave amplitude was significantly larger in the PRP group than in the PRPplus group (P = 0.0094). CR a-wave, oscillatory potentials, cone single flash, and 30 Hz flicker responses showed statistically significant within-group reductions, but no differences in between-group analyses. These results suggest that treating high-risk PDR with PRP plus IVR is effective for PDR control, and permits the use of less extensive PRP which, in turn, induces less retinal functional loss, in particular for rod-driven post-receptoral responses, than treatment with PRP alone.

Multimodal fundus imaging in choroidal osteoma.

PURPOSE: To describe the morphologic features of calcified and decalcified choroidal osteomas using multimodal imaging and correlate these findings with a previous histopathologic study. DESIGN: Retrospective observational case series. METHODS: Three patients with choroidal osteoma underwent complete ophthalmologic examination, fundus photography, and multimodal fundus imaging, including Fourier-domain optical coherence tomography (FD-OCT) and blue-light fundus autofluorescence (bAF). RESULTS: FD-OCT imaging of calcified tumors revealed a distinctive latticework pattern of reflectivity resembling the spongy bone structure seen histopathologically. On bAF the fluorescence was relatively well preserved overlying calcified tumors. In decalcified areas 2 patterns of reflectivity were identified: the first consisted of areas of relative hyperreflectivity with a lamellar appearance while the second was characterized by heterogeneous, hyperreflective, mound-like irregular areas associated with some posterior optical shadowing. Decalcified tumor areas had reduced overall fluorescence on bAF. CONCLUSION: FD-OCT demonstrated different reflectivity patterns in both calcified and decalcified portions of the choroidal osteoma, which may correspond to different stages of tumor evolution. A distinctive latticework pattern of reflectivity similar to spongy bone was seen in calcified tumors. These observations improve our knowledge of the in vivo structure of choroidal osteomas and may have implications for the diagnosis and management of this tumor.

Panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab for high-risk proliferative diabetic retinopathy.

PURPOSE: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal injection of 0.5 mg of ranibizumab (IVR) in patients with high-risk proliferative diabetic retinopathy (PDR). METHODS: Prospective study included patients with high-risk PDR and no prior laser treatment randomly assigned to receive PRP (PRP group) or PRP plus IVR (PRPplus group). PRP was administered in two sessions (weeks 0 and 2), and IVR was administered at the end of the first laser session in the PRPplus group. Standardized ophthalmic evaluations including best-corrected visual acuity (BCVA) measured according to the methods used in the Early Treatment Diabetic Retinopathy Study (BCVA), fluorescein angiography to measure area of fluorescein leakage (FLA) and optical coherence tomography (OCT) for the assessment of central subfield macular thickness (CSMT), were performed at baseline and at weeks 16 (± 2), 32 (± 2) and 48 (± 2). RESULTS: Twenty-nine of 40 patients (n = 29 eyes) completed the 48-week study follow-up period. At baseline, mean ± SE FLA (mm(2)) was 9.0 ± 1.3 and 11.7 ± 1.3 (p = 0.1502); BCVA (logMAR) was 0.31 ± 0.05 and 0.27 ± 0.06 (p = 0.6645); and CSMT (µm) was 216.3 ± 10.7 and 249.4 ± 36.1 (p = 0.3925), in the PRP and PRPplus groups, respectively. There was a significant (p < 0.05) FLA reduction at all study visits in both groups, with the reduction observed in the PRPplus group significantly larger than that in the PRP group at week 48 (PRP = 2.9 ± 1.3 mm(2) ; PRPplus = 5.8 ± 1.3 mm(2) ; p = 0.0291). Best-corrected visual acuity worsening was observed at 16, 32 and 48 weeks after treatment in the PRP group (p < 0.05), while no significant BCVA changes were observed in the PRPplus group. A significant CSMT increase was observed in the PRP group at all study visits, while a significant decrease in CSMT was observed in the PRPplus group at week 16, and no significant difference in CSMT from baseline was observed at weeks 32 and 48. CONCLUSIONS: Intravitreal ranibizumab after PRP was associated with a larger reduction in FLA at week 48 compared with PRP alone in eyes with high-risk PDR, and the adjunctive use of IVR appears to protect against the modest visual acuity loss and macular swelling observed in eyes treated with PRP alone.

Ocular findings in a patient with Castleman's disease before and after treatment with immunosuppression and plasmapheresis.

A 12-year-old girl with a 3-month history of epistaxis and Castleman's disease presented with blurred vision in both eyes for 2 weeks. Indirect ophthalmoscopy revealed a blurred optic disc margin, venous engorgement and tortuosity, intraretinal hemorrhages and cotton wool spots, and serous detachment of the neurosensory retina in the posterior pole of each eye. Fluorescein angiography and laboratory tests revealed abnormalities consistent with the clinical examination. Six months following institution of immunosuppressive treatment, cryoglobulin levels decreased and visual acuity and funduscopic abnormalities were markedly improved. However, a few microaneurysms, retinal hemorrhages, and venous engorgement and tortuosity persisted. One month after the cessation of immunosuppressive treatment, symptoms related to the hyperviscosity syndrome recurred and the patient was treated with one session of plasmapheresis. One month after the plasmapheresis, the patient's symptoms resolved, laboratory values were normal, visual acuity was 20/15 in both eyes, and the funduscopic examination of each eye was unremarkable.

Multimodal fundus imaging in Best vitelliform macular dystrophy.

BACKGROUND: Best vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects. METHODS: Comparative study including seven patients with BVMD (14 eyes) and seven age-matched healthy subjects (14 eyes). All participants were submitted to complete ophthalmological examination, fundus photography, and standardized multimodal fundus imaging protocol including Fourier-domain optical coherence tomography (Fd-OCT) combined with near-infrared reflectance and blue-light fundus autofluorescence (FAF). RESULTS: In two eyes in the "subclinical" stage, Fd-OCT revealed thickening of the middle highly reflective layer (HRL) localized between the photoreceptors' inner/outer segments junction (inner-HRL) and RPE/Bruch's membrane reflective complex (outer-HRL) throughout the macula. In one eye in the "vitelliform" stage, a homogeneous hyper-reflective material on Fd-OCT was observed between the middle-HRL and outer-HRL; this material presented increased fluorescence on FAF. The outer nuclear layer (ONL) was thinned in the central macula and subretinal fluid was not identified in these earlier disease stages. In patients of "pseudohypopyon" (two eyes), "vitelliruptive" (eight eyes) and "atrophic" (one eye) stages, Fd-OCT revealed a variety of changes in the middle- and inner-HRLs and thinning of ONL. These changes were found to be associated with the level of visual acuity observed. Thickening of the middle-HRL was observed beyond the limits of the clinically evident macular lesion in all eyes. CONCLUSIONS: Multimodal fundus imaging demonstrated thickening of the reflective layer corresponding to the photoreceptors' outer segments throughout the macula with no subretinal fluid accumulation as the earliest detectable feature in BVMD. Changes detected in the photoreceptors' reflective layers (middle- and inner- HRLs) and ONL thinning seemed to be progressive with direct implications for the level of visual acuity impairment observed among the different stages of the disease.