Unusual non-nanophthalmic uveal effusion syndrome with histologically normal scleral architecture: a case report.

BACKGROUND: To report an unusual case of non-nanophthalmic uveal effusion syndrome (UES) with histologically normal sclera but responsive to scleral resection. CASE PRESENTATION: A73-year-old man presented with a bullous retinal detachment without ciliochoroidal detachment on funduscopic examination of the right eye. The axial length of both eyes was normal. Extensive investigations for possible causes of exudative retinal detachment were performed with unremarkable results except for choroidal hyperpermeability on indocyanine green angiography (ICGA). Ultrasound biomicroscopy (UBM) revealed scleral thickening with peripheral choroidal elevation leading to the diagnosis of UES. Partial thickness sclerectomy and sclerotomy was performed resulting in complete retinal reattachment, reduction of choroidal hyperpermeability on ICGA and improvement of visual acuity. However, histological studies of the excised sclera revealed no scleral architectural changes or abnormal deposits. CONCLUSIONS: The diagnosis of UES in non-nanophthalmic eyes is challenging. Thorough systemic and ocular investigations are critical to rule out other etiologies. UBM can be helpful to evaluate scleral thickness and anterior choroid in equivocal cases. Our case was unique in that, although the sclera was thick, no abnormal microscopic scleral architecture could be identified. Misdiagnosis may lead to different surgical procedures such as vitrectomy resulting in unfavorable outcomes.

PROGRESSION OF MACULAR ATROPHY IN EYES WITH TYPE 1 NEOVASCULARIZATION AND AGE-RELATED MACULAR DEGENERATION RECEIVING LONG-TERM INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: An Optical Coherence Tomographic Angiography Analysis.

PURPOSE: To evaluate the size and location of macular atrophy in eyes with Type-1 neovascularization (NV) and age-related macular degeneration receiving chronic intravitreal anti-vascular endothelial growth factor therapy. METHODS: A retrospective review of a case series of 27 eyes with Type-1 NV and retinal pigment epithelial detachment (PED) having a minimum of 12 months follow-up was performed. Demographic information and visual acuity at baseline and the final follow-up were collected. Spectral-domain optical coherence tomography (OCT) and near-infrared reflectance were analyzed at 6-month intervals to detect and measure macular atrophy. Location and area (in square millimeter) of macular atrophy were measured using Heidelberg software tools. Also, OCT angiography was used to colocalize the area of Type-1 NV flow versus the location of atrophy. RESULTS: Twenty-seven eyes of 27 patients were included in this analysis. The median visual acuity was 20/50, mean age was 82.7 years, and mean number of injections was 29.5. A larger percentage of eyes (59.3%) developed atrophy predominantly eccentric to the PED versus predominantly overlying the PED (11.1%) when measured with spectral-domain OCT and near-infrared imaging. At the final follow-up, there was a larger area of atrophy surrounding the fibrovascular PED (mean, 3.326 mm) than overlying it (mean, 0.542 mm), and this was statistically significant (P = 0.0118). En-face OCT images were overlaid with OCT angiography in 11 eyes, and a predominantly eccentric pattern of atrophy was identified in 9 of 11 eyes. Using this method, the mean area of atrophy predominantly overlying the Type-1 NV was 1.652 mm (range of 0-10.464 mm), whereas the area of atrophy predominantly eccentric to the neovascular complex was 4.345 mm (range of 0.705-13.758 mm), and this was statistically significant (P = 0.0465). The average rate of atrophy progression was 1.04 mm/year (SD 0.938). CONCLUSION: With long-term anti-vascular endothelial growth factor therapy for eyes with Type-1 NV secondary to age-related macular degeneration, macular atrophy tends to develop predominantly eccentric to the PED and the neovascular flow imaged on OCT angiography. With chronic vascular endothelial growth factor suppression, Type-1 NV may evolve into a multilayered PED that may confer a protective effect to the overlying retinal pigment epithelium and outer retina.

BIOMARKERS OF NEOVASCULAR ACTIVITY IN AGE-RELATED MACULAR DEGENERATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the qualitative and quantitative features of choroidal neovascular (NV) membranes in age-related macular degeneration using optical coherence tomography angiography in patients with active and quiescent NV lesions before and after treatment with anti-vascular endothelial growth factor. METHODS: Macular optical coherence tomography angiography images were obtained using RTVue XR Avanti with AngioVue. Morphologic features and quantitative measurements of the NV lesion were analyzed using en face projection images. The NV lesion was subdivided into inner segment and outer fringe for further fractal dimension analysis. RESULTS: In a series of 31 eyes, 11 eyes with active NV lesions at baseline and after consecutive follow-up after treatment with anti-vascular endothelial growth factor therapy and 20 eyes with quiescent NV lesions were included in this study. Morphologically, all the quiescent NV lesions versus 63.6% of the active NV lesions demonstrated a prominent central vessel and active leasions demonstrated a greater rate of small vessels branching (82%) and peripheral arcades (82%) than quiescent lesions (30% and 40% respectively) and this was statistically significant. The lesion area and vessel density was not statistically significantly different after treatment or versus quiescent lesions although the latter lesions were reduced in area. Lesion pattern complexity measured by the fractal dimension was statistically significantly lower in the inner part of the lesion after treatment and statistically significantly lower in the total lesion of the quiescent NV compared with the active NV. CONCLUSION: Optical coherence tomography angiography is a new, noninvasive imaging modality that can be used to perform qualitative and quantitative analyses of NV lesions. In the future, OCT angiography may provide biomarkers of activity and guide the evaluation and treatment and monitoring of neovascularization in age-related macular degeneration.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

REGRESSION OF TYPE 2 NEOVASCULARIZATION INTO A TYPE 1 PATTERN AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To study eyes with Type 2 (subretinal) neovascularization (NV) secondary to neovascular age-related macular degeneration (nAMD) that shows lesion regression into a Type 1 (subretinal pigment epithelium) pattern after treatment with intravitreal anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Retrospective consecutive case series. Patients showing regression of Type 2 neovascularization into a Type 1 pattern after envelopment by retinal pigment epithelium were included in this analysis. A review of the clinical records and multimodal imaging of these cases was performed at baseline, 1, 3, 6, and 12 months. Demographic data, best-corrected visual acuity (BCVA), color fundus photography, fundus autofluorescence (FAF), fluorescein angiography, near-infrared reflectance (NIR), and structural spectral-domain optical coherence tomography (SD-OCT) were reviewed and analyzed. When available, optical coherence tomography angiography images were analyzed as well. RESULTS: Ten eyes of 9 patients (6 males) diagnosed with treatment-naive pure Type 2 neovascularization secondary to nAMD were included. The mean age was 80.7 years (SD ± 4.30). Mean best-corrected visual acuity expressed in logMAR (Snellen) was 0.45 ± 0.20 (20/55) at baseline and significantly improved to 0.22 ± 0.13 (20/32) at 3-month follow-up (P-value: 0.007). At baseline, color photographs and fundus autofluorescence showed a pigment ring around the neovascular lesion in 6 eyes. A hyperreflective ring was visible on NIR in all eyes at 3-month follow-up. Color photographs showed a tessellated fundus appearance in 9 of the 10 eyes. Serial structural spectral-domain optical coherence tomography scans showed the gradual regression of the Type 2 lesions into a Type 1 pattern with envelopment by the retinal pigment epithelium. En face and cross-sectional optical coherence tomography angiography showed baseline subretinal flow patterns which, after treatment, exhibited reduced flow beneath an intact hyperreflective retinal pigment epithelium (RPE) band. CONCLUSION: Pure Type 2 lesions are infrequent in nAMD, often leading to poor visual outcomes related to subretinal fibrosis. We describe an alternate regression pattern occurring in eyes with early Type 2 lesions treated with intravitreal anti-vascular endothelial growth factor therapy in which the neovascular tissue is enveloped by retinal pigment epithelium producing a Type 1 pattern. These eyes appear to have better visual outcomes than typically seen with Type 2 lesions related to reduced outer retinal damage.

CHOROIDAL CHANGES ASSOCIATED WITH SEROUS MACULAR DETACHMENT IN EYES WITH STAPHYLOMA, DOME-SHAPED MACULA OR TILTED DISK SYNDROME.

PURPOSE: To study the relationship of choroidal abnormalities with serous retinal detachment (SRD) in eyes with staphyloma, dome-shaped macula, or tilted disk syndrome. METHODS: Group 1, 28 eyes of 20 patients with staphyloma/dome-shaped macula/tilted disk syndrome associated with SRD was compared with Group 2, 30 eyes of 20 patients, with staphyloma/dome-shaped macula/tilted disk syndrome but without SRD. Radial and en-face optical coherence tomography and choroidal analysis were performed. RESULTS: Group 1 had a thicker mean subfoveal choroidal thickness (161 µm vs. 92 µm, P < 0.05) and a greater variation in choroidal thickness (112 µm vs. 76 µm, P > 0.05) compared with eyes of Group 2. Focal abrupt changes in choroidal thickness were more commonly seen in Group 1 versus eyes in Group 2 (90% vs. 30%, P < 0.05) and this area of abrupt change was located within or at the edge of the SRD in 64% of eyes. Large choroidal vessels (pachyvessels) (82% located within the area of SRD) were always associated with the presence of SRD. CONCLUSION: An abrupt transition in choroidal thickness may be involved in the pathogenesis of SRD. In some cases, a radial scan pattern may better demonstrate mild SRD, choroidal contours and the focal choroidal variations than horizontal or vertical raster scan patterns.

AN UPDATED STAGING SYSTEM OF TYPE 3 NEOVASCULARIZATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To comprehensively investigate spectral domain optical coherence tomography features associated with Type 3 neovascularization and determine the prevalence of each feature and to develop an updated staging system for Type 3 neovascularization based on spectral domain optical coherence tomography findings. METHODS: The authors retrospectively analyzed 34 eyes with new-onset Type 3 neovascularization. Spectral domain optical coherence tomography images at onset of Type 3 neovascularization, immediately after the first injection, and at the final quiescent visit were analyzed for the presence of specific optical coherence tomography features. In addition, when available, optical coherence tomography images from the visit before onset were studied. RESULTS: Among 18 eyes with preonset optical coherence tomography, 77.8% had preexisting intraretinal hyperreflective foci (precursor lesion). In the same group of eyes, 44.4% and 27.8% exhibited outer plexiform layer disruption and outer plexiform layer downward deflection, respectively. At the onset of detectable Type 3 neovascularization, all 34 eyes demonstrated a hyperreflective focus with cystoid macular edema and 85.3% exhibited disruption of the retinal pigment epithelium. Serous pigment epithelial detachment and subretinal fluid were present in 67.6% and 23.5% of eyes at onset, respectively. The rate of cystoid macular edema decreased from 100% to 17.6% after a single injection. At the final quiescent visit, focal atrophy at the site of Type 3 lesions, as evidenced by outer retinal and retinal pigment epithelium disruption developed in 88.2% and 52.9% of eyes, respectively. CONCLUSION: An updated staging system of Type 3 lesions was developed based on spectral domain optical coherence tomography findings. A precursor stage consists of a punctate hyperreflective focus in the outer retina. The subtle detection of associated outer plexiform layer disruption and downward deflection may indicate that this precursor lesion is more likely to progress to an active Type 3 neovascular lesion. Stage 1 consists of a larger intraretinal hyperreflective lesion associated with cystoid macular edema but without outer retinal disruption. Stage 2 is notable for outer retinal disruption that occurs with retinal pigment epithelium disruption in most of the cases. Stage 3 is defined by an intraretinal hyperreflective lesion that extends through the retinal pigment epithelium to vascularize a drusenoid pigment epithelial detachment creating a serous component of the pigment epithelial detachment.

Stability of Bevacizumab Divided in Multiple Doses for Intravitreal Injection.

OBJECTIVE: To investigate the stability of bevacizumab in multiple doses divided from a single-use vial for intravitreal injection after storage at 4°C for up to six months and under drug transfer condition in tropical climate. MATERIAL AND METHOD: Five syringes (0.1 mL, 2.5 mg) of bevacizumab were withdrawn each from five new bevacizumab single-use vials (4 mL, 100 mg) under sterile technique. The concentration of bevacizumab in each syringe was measured at two dilutions (2 x 10(6) and 4 x 10(6) fold) using enzyme-linked immunosorbent assay at baseline and after storage at 4°C for 1-, 3-, and 6-month. Each assay was performed at least twice. To simulate the drug transfer condition, bevacizumab was placed in a brown plastic bag and put in another transfer plastic bag with an ice cube for 30 minutes prior to the assay at 1-, 3-, and 6-month. RESULTS: The concentrations of bevacizumab (mean ± standard deviation) at baseline, 1-, 3-, and 6-month were 26.24 ± 1.95, 25.43 ± 3.80, 27.87 ± 2.81, and 24.25 ± 2.00 mg/mL, respectively. The lowest lower limit of 95% confidence interval for the mean concentration was 23.32 mg/mL at 6-month storage, which was 89% of the mean baseline concentration and considered to be non-inferior to the baseline concentration. CONCLUSION: Bevacizumab in a single-use vial could be divided into multiple small doses for intravitreal injection with sufficient stability when refrigerated at 4°C for up to six months and under the drug transfer condition in tropical climate.

Enhanced depth imaging spectral-domain optical coherence tomography of the choroid in Thai population.

OBJECTIVE: To examine subfoveal choroidal thickness (SFCT) in Thai population using enhanced depth imaging spectral- domain optical coherence tomography (EDI-OCT) and to study its correlation with foveal retinal pigment epithelium thickness (FRPE), central neurosensory retinal thickness (CNRT), age, and refraction. MATERIAL AND METHOD: Four hundred eighty eyes from 240 subjects without glaucoma, retinal, or choroidal diseases underwent scanning of the retina and choroid using EDI-OCT SFCT FRPE, and CNRT measurements were based on the 1:1 micron images and wereperformed by two independent observers. The reliability ofmeasurements between the observers was evaluated by intraclass correlation coefficient (ICC). The correlations of SFCT with FRPE, CNRT, age, and refractive error were analyzed RESULTS: The mean age of the subjects was 36.22 years (range 20-81years). The means (95% reference intervals) of SFCT, CNRT andFRPE were 294.02 µm (137.14-450.90 µm), 174.22 µm (141.82-206.62 µm), and 41.94 µm (34.65-49.23 µm), respectively. SFCT and CNRThad excellent reliability between the two observers [ICC = 0.947 (95% CI, 0.918-0.963) and 0.929 (95% CI, 0.906-0.945), respectively], while FRPE showed good reliability [ICC = 0. 729 (95% CI, 0.637-0.793)]. SFCT had a low positive correlation with FRPE (r = 0.179, p<0. 0001) but not with CNRT (p = 0.317). SFCT showed a positive correlation with refraction (r = 0.338, p<0.0001) and a negative correlation with age (r = -0.166, p<0.0001). Regression analysis suggested that the SFCT decreased by 12.23 pm per one decade oflife and by 11.42 pm per one diopter of myopia. CONCLUSION: Normal values of SFCT in Thai population were obtained SFCT significantly decreased with older age and higher myopia. SFCT was associated with FRPE, reflecting the same vascular supply of the choroid and retinal pigment epithelium. When measured with our technique based on the 1:1 micron images, the reliability ofSFCT measurement was very high despite highly morphologic inter-individual variations.

Klebsiella pneumoniae Endophthalmitis with Subretinal Abscess: A Case Series and Review of the Literature.

This study assessed prognostic factors and the role of vitrectomy in patients with subretinal abscesses secondary to K. pneumoniae endophthalmitis. We reviewed published studies, including three cases from our cohort. Among 50 eyes, 26 had poor visual outcomes (final visual acuity <20/800, eyeball removal, or phthisis bulbi). Poor outcomes correlated with delayed ocular symptom-to-diagnosis time, initial visual acuity <20/800, severe vitritis, and macular involvement of abscesses (p < 0.001, p = 0.008, p < 0.001, and p = 0.033, respectively). Vitrectomy had a trend towards reducing eyeball removal and phthisis bulbi rates compared with non-vitrectomy (10.8% vs 30.8%, p = 0.181). However, the final visual acuity was not different and the rate of retinal detachment tended to be higher in vitrectomized eyes (45.9% vs 15.4%, p = 0.095). The study suggested that vitrectomy and drainage of K. pneumoniae subretinal abscesses could be avoided in patients with a mild degree of vitritis.

Effect of fenestrated sterile drape and face mask on bacterial dispersion toward the periocular area during intravitreal injection.

This experimental crossover study was performed to investigate whether fenestrated surgical drapes (covering the nose and mouth but with an opening over the periorbital area) with or without patients' surgical face masks increase periorbital bacterial dispersion during simulated intravitreal injection conditions. Each of the 16 healthy volunteers performed 14 scenarios involving different mask and drape conditions in both silent and speaking situations. In each scenario, the subject lay down flat on the back with a blood agar plate being held at the inferior orbital rim perpendicular to the face to capture airflow from breathing/speaking. Another blood agar plate placed 50 cm away from the subject served as an experimental control. A total of 224 experiments were performed. Speaking situations significantly showed more colony forming units (CFUs) compared with their controls (P = 0.014). There were no significant differences in CFUs between wearing vs not wearing the masks (P = 0.887 for speaking and P = 0.219 for silent) and using vs not using the drapes (P = 0.941 for speaking and P = 0.687 for silent). Reusable and disposable drapes were also not significantly different (P = 1.00 for speaking and P = 0.625 for silent). Streptococcus spp., the oropharyngeal microbiota, were only cultivated from speaking scenarios. While refraining from speaking (for both practitioners and patients) is the mainstay of reducing bacterial dispersion and risks of post-injection endophthalmitis, the use of fenestrated surgical drapes or patients' face masks did not significantly affect the amount of bacterial dispersion toward the periorbital area.

Optical Coherence Tomography Angiography Biomarkers in Thai Patients With Diabetic Nephropathy: A Diabetic Eye and Kidney Diseases (DEK-D) Study.

Purpose: To identify optical coherence tomography angiography (OCTA) biomarkers to predict the diabetic nephropathy (DN) and their associations with 24-hour urine albumin levels in diabetic patients. Methods: This cross-sectional, observational study examined 186 eyes from 93 individuals subdivided into three groups according to 24-hour urine albumin levels: no DN, early DN, and late DN. Vessel density (VD), fractal dimension, foveal avascular zone area, intercapillary area, central retinal thickness, and subfoveal choroidal thickness were measured from OCTA images to determine their association with the DN stages. Results: VD values of the superficial capillary plexus, deep capillary plexus, and whole retina were significantly lower in the early DN group compared to the no DN group (adjusted P = 0.042, 0.016, and 0.008, respectively). VD values for the deep capillary plexus and whole retina were significantly decreased in the late DN group compared to the no DN group (adjusted P = 0.025 and 0.021, respectively). Mean fractal dimension, intercapillary area, foveal avascular zone area, central retinal thickness, and subfoveal choroidal thickness were not statistically different among the three groups. Conclusions: VD may be a useful parameter for the early non-invasive screening of DN. Further studies in larger populations are needed to establish a cutoff value for detection. Translational Relevance: This study investigated the association of each retinal vasculature measurement by OCTA and diabetic nephropathy status which could serve as an alternative way to screen for albuminuria.

Myopic macular schisis: Insights into distinct morphological subtypes and novel biomechanical hypothesis.

PURPOSE: To analyze the features of myopic macular schisis (MMS) in different retinal layers and to explore the role of Müller cells in the pathophysiology of such condition. METHODS: Spectral-domain optical coherence tomography (SD-OCT) images of myopic eyes with staphyloma and macular schisis were reviewed. The morphological features of MMS were analyzed and correlated with their geographical location in the parafoveal and perifoveal region. A biomechanical model was adopted to explain MMS morphological differences. The effect of the different schisis subtypes with best corrected visual acuity (BCVA) was also explored. RESULTS: A total of 36 eyes from 26 patients were included in this study. MMS was classified into inner, middle and outer retinal subtypes. The prevalence of middle retinal schisis was significantly lower in the parafovea, within a central 3 mm-diameter circle (p < 0.001) centered at the fovea . The prevalence of inner retinal schisis was significantly higher outside the central 3-mm diameter circle, in the perifoveal region (p < 0.001). No significant differences were noted in the prevalence of outer retinal schisis for these two locations (p = 0.475). The presence of middle retinal schisis within the central 3-mm diameter circle showed a weak association with lower BCVA (p = 0.058). The presence of outer retinal schisis within the central 3-mm diameter circle was significantly related with lower BCVA (p = 0.024). CONCLUSION: Three major forms of MMS are distinguished: inner, middle and outer retinal schisis. This classification may have clinical importance as only the outer grade of schisis was associated with vision loss.

Subretinal gnathostomiasis: A successful focal laser photocoagulation for a living parasite.

PURPOSE: To report a case of subretinal gnathostomiasis presenting with progressive subretinal tracts of a living parasite and successfully treated with focal laser photocoagulation. METHOD: Observational case report. PATIENT: A 29-year-old Thai male complained of blurred vision and floaters in his left eye for two weeks. An ocular examination showed multiple, whitish, subretinal tracks at the superotemporal retina. After 5 days of oral albendazole, a moving parasite was confirmed by multimodal retinal imaging. An immunoblotting analysis was positive for Gnathostoma species. RESULT: The patient was treated by laser photocoagulation with frequency-doubled Nd:YAG laser around and over the parasite. Oral albendozole was continued and naproxen was prescribed for four weeks. His vision improved to 20/20 and the inflammation subsided completely within three months. The patient has been followed for five years without local and systemic complications. CONCLUSIONS: Focal laser photocoagulation without systemic steroids could be a successful treatment for active subretinal gnathostomiasis with a satisfactory safety profile in a long-term follow-up.

Optical Coherence Tomography Features for Identifying Posttreatment Complete Polypoidal Regression in Polypoidal Choroidal Vasculopathy.

PURPOSE: To determine accuracy and relative risk (RR) of posttreatment optical coherence tomography (OCT) features in identifying complete or incomplete polypoidal regression in polypoidal choroidal vasculopathy (PCV). DESIGN: Validity analysis. METHODS: Treatment-naive PCV eyes undergoing OCT and indocyanine green angiography (ICGA) at baseline and posttreatment were included. Two graders confirmed diagnosis and identified posttreatment complete or incomplete regression on ICGA. Two other graders classified OCT characteristics of pigment epithelial detachment (PED) (polypoidal lesion) based on 5 prespecified features: "A," no PED; "B," PED with internal homogeneous reflectivity with predominant "BUN" (blended retinal pigment epithelium with underlying structure) sign; "C," PED with internal homogeneous reflectivity with minimal "BUN"; "D," heterogeneous PED; and "E," PED with hyporeflectivity. RESULTS: Among 130 polypoidal lesions (65 pretreatment and 65 posttreatment) of 39 PCV eyes (39 patients; 54% female; mean age±SD: 64.6±8.2), all pretreatment lesions showed feature D on OCT. Posttreatment lesions with complete regression (31 lesions) showed OCT features A, B, C, D, and E in 32%, 45%, 13%, 10%, and 0%, respectively. Posttreatment lesions with incomplete regression (34 lesions) showed OCT features A, B, C, D, and E in 0%, 6%, 15%, 79%, and 0%, respectively. Presence of either feature A or B had highest accuracy (86%; 95% confidence interval: 75%-93%); 77% sensitivity; 94% specificity; RR 5.0 (3.5-7.1, P<0.001) for complete regression. Presence of feature D had highest accuracy (85%; 95% confidence interval: 74%-92%); 79% sensitivity; 90% specificity; RR 4.6 (3.0-6.9, P<0.001) for incomplete regression. CONCLUSIONS: Without ICGA, OCT features could provide high accuracy in identifying posttreatment complete or incomplete polypoidal regression in PCV.

Long-term visual and anatomic outcomes of patients with peripapillary pachychoroid syndrome.

BACKGROUND/AIMS: To analyse the long-term anatomic and visual outcomes of patients with peripapillary pachychoroid syndrome (PPS), a recently described entity in the pachychoroid disease spectrum. METHODS: This study retrospectively included patients from several retina centres worldwide. Visual acuity (VA), retinal thickness and choroidal thickness at baseline, 6 months and final follow-up were assessed. Temporal trends in VA and anatomic characteristics were evaluated. Visual and anatomic outcomes in eyes that were observed versus those that were treated were analysed. RESULTS: Fifty-six eyes of 35 patients were included with mean follow-up of 27±17 months. Median VA was 20/36 at baseline and remained stable through follow-up (p=0.77). Retinal thickness significantly decreased subfoveally (p=0.012), 1.5 mm nasal to the fovea (p=0.002) and 3.0 mm nasal to the fovea (p=0.0035) corresponding to areas of increased thickening at baseline. Choroidal thickness significantly decreased subfoveally (p=0.0030) and 1.5 mm nasal to the fovea (p=0.0030). Forty-three eyes were treated with modalities including antivascular endothelial growth factor injection, photodynamic therapy, and others. VA remained stable in treated eyes over follow-up (p=0.67). An isolated peripapillary fluid pocket in the outer nuclear layer was characteristic of PPS. CONCLUSION: Patients with PPS experienced decreased retinal oedema and decreased choroidal thickening throughout the course of disease. While some patients experienced visual decline, the overall visual outcome was relatively favourable and independent of trends in retinal or choroidal thickening.

Non-Neovascular Pachychoroid Disease Mimicking Exudative Age-Related Macular Degeneration.

PURPOSE: To describe a case of pachychoroid disease most compatible with central serous chorioretinopathy (CSC) presented with a large relapsing retinal pigment epithelial detachment (PED) associated with only a small amount of subretinal fluid (SRF) in the background of macular drusen in an elderly patient mimicking neovascular age-related macular degeneration (AMD). METHODS: This was a review of 32 months of the clinical course and findings on multimodal imaging including fundus photography, optical coherence tomography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography angiography (OCTA). RESULTS: A large relapsing PED sometimes with small amount of SRF at its apex was found in the background of macular drusen in the right eye of a 63-year-old Thai woman. The relapses of the PED showed an apparent association with recent steroid exposure. Multimodal imaging demonstrated the characteristics of pachychoroid diseases with pachyvessels and choroidal hyperpermeability. The PED and SRF responded well to anti-vascular endothelial growth factor (anti-VEGF) therapy, especially aflibercept, but could also be spontaneously resolved without anti-VEGF. No evidence of choroidal neovascularization or polyps could be identified by serial FFA, ICGA, and OCTA even when the retinal pigment epithelium was completely flat with no obscuration by PED. CONCLUSIONS: A large PED with little SRF could present signs of CSC. This clinical presentation could be confused with neovascular AMD, and multimodal retinal imaging was crucial to guide correct diagnosis and management.

Recent advances in wide field and ultrawide field optical coherence tomography angiography in retinochoroidal pathologies.

Introduction: With the advent of wide field (WF) and ultra-wide field (UWF) imaging in color fundus photography and fluorescein angiography (FA), the importance of an expanded field-of-view (FOV) has been illustrated for early detection of several chorioretinal disorders. The need to bring similar utility to optical coherence tomography angiography (OCTA) is imperative.Areas covered: For this review, we explored all research items with WF or UWF on Pubmed Central and Google Scholar. Software-based methods included algorithms for motion correction, artifact reduction, image pre-processing, post-processing and montage protocols while hardware methods included swept-source OCTA, faster scanning sources, hardware-based motion tracking and image registration, scanning sources with faster speeds and lower resolution. For various disorders such as diabetic retinopathy, uveitis, vascular disorders, among others, the increased FOV showed demonstrably increased detection rates and diagnostic yield.Expert opinion: Increased FOV in OCTA imaging is a meaningful and impactful step in ophthalmic imaging. Overcoming the hardware-based limitations can potentially yield higher FOV without loss of important details. In addition to improvements in the hardware and available equipment, better software tools and image processing algorithms may greatly enhance the utility of UWF OCTA in care of patients with various retinochoroidal diseases.

In-Person Verification of Deep Learning Algorithm for Diabetic Retinopathy Screening Using Different Techniques Across Fundus Image Devices.

Purpose: To evaluate the clinical performance of an automated diabetic retinopathy (DR) screening model to detect referable cases at Siriraj Hospital, Bangkok, Thailand. Methods: A retrospective review of two sets of fundus photographs (Eidon and Nidek) was undertaken. The images were classified by DR staging prior to the development of a DR screening model. In a prospective cross-sectional enrollment of patients with diabetes, automated detection of referable DR was compared with the results of the gold standard, a dilated fundus examination. Results: The study analyzed 2533 Nidek fundus images and 1989 Eidon images. The sensitivities calculated for the Nidek and Eidon images were 0.93 and 0.88 and the specificities were 0.91 and 0.85, respectively. In a clinical verification phase using 982 Nidek and 674 Eidon photographs, the calculated sensitivities and specificities were 0.86 and 0.92 for Nidek along with 0.92 and 0.84 for Eidon, respectively. The 60°-field images from the Eidon yielded a more desirable performance in differentiating referable DR than did the corresponding images from the Nidek. Conclusions: A conventional fundus examination requires intense healthcare resources. It is time consuming and possibly leads to unavoidable human errors. The deep learning algorithm for the detection of referable DR exhibited a favorable performance and is a promising alternative for DR screening. However, variations in the color and pixels of photographs can cause differences in sensitivity and specificity. The image angle and poor quality of fundus photographs were the main limitations of the automated method. Translational Relevance: The deep learning algorithm, developed from basic research of image processing, was applied to detect referable DR in a real-word clinical care setting.

Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P < 0.025), which is consistently significant across several linkage statistics. The most suggestive marker D3S1565 (Zlr > 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.