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Abstract Objective To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges. Methods This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination. Results Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively. Conclusion Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM.

Purpose: To determine the clinical and imaging biomarkers of the response to half-dose photodynamic therapy (HD-PDT) in patients with central serous chorioretinopathy (CSC) Methods: Clinical records and baseline ophthalmic images of 67 chronic CSC patients who underwent HD-PDT were assessed. In addition to demographic data, optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) images were analyzed for specific biomarkers. The patients were categorized to early responder and late responder based on the time needed for complete resolution of subretinal fluid after PDT (less than 1 month vs. more than 1 month). The baseline clinical and imaging biomarkers were compared between the two groups. Results: Seventy-three eyes of 67 patients were included in the study. The mean response time to PDT was 1.63 ± 1.48 months with 82.2% (60/73) of eyes categorized as early responder. The mean response time to PDT in delayed-response group was 4.15±1.51 months. In multivariate analysis, delayed response to PDT was associated with lacking history of systemic corticosteroid consumption, lacking history of pretreatment with eplerenone or acetazolamide before PDT and presence of hyperreflective foci in baseline OCT images (all p values < 0.05). There was no association between final visual outcome and late response to PDT. Conclusion: The presence of inflammatory biomarkers such as hyperreflective foci in baseline OCT images might be indicative of resistance to PDT. Moreover, the effect of pretreatment with mineralocorticoid antagonist on the response to PDT in chronic CSC should be explored in future prospective studies.

Abstract Purpose: To compare the outcomes of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). Methods: In this retrospective comparative study, medical records of eyes with chronic CSC who underwent half-dose PDT were reviewed. A retina specialist performed FA-guided half-dose PDT, and the other performed ICGA-guided treatment. The success of applying PDT in the resolution of subretinal fluid was compared between the FA- and ICGA-guided methods. Results: Eighty-two eyes of 73 patients (41 eyes in each group) received half-dose PDT. After half-dose PDT, a significant improvement in the best-corrected visual acuity (BCVA) was found at the time of the last follow-up in both groups (both P < 0.001), with no significant intergroup difference. Central subfield and subfoveal choroidal thicknesses decreased significantly in both groups at the last follow-up (all P < 0.05), with no significant differences between the groups. Subretinal fluid (SRF) resolved in all eyes, and no persistent SRF was detected during the follow-up period. Conclusion: FA-guided and ICG-guided half-dose PDT may have similar efficacy for the treatment of chronic CSC.

Abstract Background Mutations in ABHD12 (OMIM: 613,599) are associated with polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) syndrome (OMIM: 612674), which is a rare autosomal recessive neurodegenerative disease. PHARC syndrome is easily misdiagnosed as other neurologic disorders, such as retinitis pigmentosa, Charcot-Marie-Tooth disease, and Refsum disease, due to phenotype variability and slow progression. This paper presents a novel mutation in ABHD12 in two affected siblings with PHARC syndrome phenotypes. In addition, we summarize genotype-phenotype information of the previously reported patients with ABHD12 mutation. Methods Following a thorough medical evaluation, whole-exome sequencing was done on the proband to look for potential genetic causes. This was followed by confirmation of identified variant in the proband and segregation analysis in the family by Sanger sequencing. The variants were interpreted based on the American College of Medical Genetics and Genomics (ACMG) guidelines. Results A novel pathogenic homozygous frameshift variant, NM_001042472.3:c.601dup, p.(Val201GlyfsTer4), was identified in exon 6 of ABHD12 (ACMG criteria: PVS1 and PM2, PM1, PM4, PP3, and PP4). Through Sanger sequencing, we showed that this variant is co-segregated with the disease in the family. Further medical evaluations confirmed the compatibility of the patients’ phenotype with PHARC syndrome. Conclusions Our findings expand the spectrum of mutations in the ABHD12 and emphasize the significance of multidisciplinary diagnostic collaboration among clinicians and geneticists to solve the differential diagnosis of related disorders. Moreover, a summary based on mutations found so far in the ABHD12 gene did not suggest a clear genotype-phenotype correlation for PHARC syndrome.

Abstract This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.

Ethylene diamine tetra acetic acid (EDTA) is a chelating component that is able to diminish oxidative reactivity and can be a potential neuroprotective drug in various ocular diseases. For assessing the safety of intravitreal EDTA, 10 rabbits were allocated and divided into 5 groups. Right eyes of the animals received intravitreal EDTA (112.5, 225, 450, 900 and 1800 µg /0.1 ml). Fellow eyes were considered as controls. Clinical examinations and electroretinography (ERG) were performed at the baseline and on day 28. The enucleated eyes were subjected to hematoxylin and eosin (H&E) staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Clinical examinations, H&E staining and TUNEL assay were unremarkable. The ERG test did not exhibit any significant alteration compared to the baseline values, except for a significant decrease in just one measurement of the eyes injected with 225 µg EDTA. The mean scores of GFAP immune reactivity in the eyes injected with 112.5 and 225 µg EDTA indicated a non-significant reaction. The scores in higher doses were significant. We suggest intravitreal EDTA with a dose threshold of

Abstract The purpose of this study was to introduce a new machine learning approach for differentiation of a pachychoroid from a healthy choroid based on enhanced depth-optical coherence tomography (EDI-OCT) imaging. This study included EDI-OCT images of 103 eyes from 82 patients with central serous chorioretinopathy or pachychoroid pigment epitheliopathy, and 103 eyes from 103 age- and sex-matched healthy subjects. Choroidal features including choroidal thickness (CT), choroidal area (CA), Haller layer thickness (HT), Sattler-choriocapillaris thickness (SCT), and the choroidal vascular index (CVI) were extracted. The Haller ratio (HR) was obtained by dividing HT by CT. Multivariate TwoStep cluster analysis was performed with a preset number of two clusters based on a combination of different choroidal features. Clinical criteria were developed based on the results of the cluster analysis, and two independent skilled retina specialists graded a separate testing dataset based on the new clinical criteria. TwoStep cluster analysis achieved a sensitivity of 1.000 (95-CI: 0.938–1.000) and a specificity of 0.986 (95-CI: 0.919–1.000) in the differentiation of pachy- and healthy choroid. The best result for identification of pachychoroid was obtained for a combination of CT, HR, and CVI, with a correct classification rate of 0.993 (95-CI: 0.980–1.000). Based on the relative variable importance (RVI), the cluster analysis prioritized the choroidal features as follows: HR (RVI: 1.0), CVI (RVI: 0.87), CT (RVI: 0.70), CA (RVI: 0.59), and SCT (RVI: 0.27). After performing a receiver operating characteristic curve analysis on the cluster membership variable, a cutoff point of 389 µm and 0.79 was determined for CT and HR, respectively. Based on these clinical criteria, a sensitivity of 0.793 (95-CI: 0.611–0.904) and a specificity of 0.786 (95-CI: 0.600–0.900) and 0.821 (95-CI: 0.638–0.924) were achieved for each grader. Cohen's kappa of inter-rater reliability was 0.895. Based on an unsupervised machine learning approach, a combination of the Haller ratio and choroidal thickness is the most valuable factor in the differentiation of pachy- and healthy choroids in a clinical setting.

Abstract Purpose: To assess the changes in optic nerve head and macular microvascular networks after acute intraocular pressure (IOP) rise in healthy eyes versus the eyes of diabetic patients. Methods: In this prospective, interventional, comparative study, 24 eyes of 24 adults including 12 eyes of healthy nondiabetic subjects and 12 eyes with mild or moderate non-proliferative diabetic retinopathy (NPDR) were enrolled. IOP elevation was induced by a suction cup attached to the conjunctiva. IOP and optical coherence tomography angiographic (OCTA) images of the optic disc and macula were obtained before and immediately after the IOP rise. Results: Baseline and post-suction IOPs were not significantly different between the two groups (all P > 0.05). The mean IOP elevation was 13.93 ± 3.41 mmHg among all eyes and was statistically significant as compared to the baseline in both groups (both P < 0.05). After IOP elevation, healthy eyes demonstrated a reduction in the vessel density in the whole image deep and superficial capillary plexuses and parafoveal deep capillary plexus (DCP) (all P < 0.05). In diabetic retinopathy, foveal vessel density at DCP decreased significantly following IOP rise (P = 0.003). In both groups, inside disc vessel density decreased significantly after IOP rise (both P < 0.05), however, no significant change was observed in peripapillary vessel density (both P > 0.05). Conclusion: Acute rise of IOP may induce different levels of microvascular changes in healthy and diabetic eyes. Optic disc microvasculature originating from the posterior ciliary artery may be more susceptible to IOP elevation than that of retinal microvasculature.

Abstract The purpose of current study was to evaluate different optical coherence tomography angiography (OCTA) metrics in eyes with diabetic retinopathy with and without diabetic macular edema (DME). In this retrospective study, macular OCTA images of eyes with non-proliferative or proliferative diabetic retinopathy were evaluated. Vascular density, vascular complexity and non-perfusion densities were compared between eyes with and without DME. One-hundred-thirty-eight eyes of 92 diabetic patients including 49 eyes with DME were included. In multivariate analysis, the presence of DME was positively associated with geometric perfusion deficit (GPD) in superficial capillary plexus (SCP), capillary non-perfusion (CNP) of SCP, and GPD in deep capillary plexus (DCP) (all P

Abstract Intravitreal methotrexate (MTX) has been proven to be an effective treatment for various intraocular diseases. In this article, a comprehensive review was performed on intravitreal applications of methotrexate. Different aspects of the administration of intravitreal MTX for various clinical conditions such as intraocular tumors, proliferative vitreoretinopathy, diabetic retinopathy, age-related macular degeneration, and uveitis were reviewed and the adverse effects of intravitreal injection of MTX were discussed. The most common indications are intraocular lymphoma and uveitis. Other applications remain challenging and more studies are needed to establish the role of intravitreal MTX in the management of ocular diseases.

Abstract Candida spp. is the most common cause of endogenous fungal endophthalmitis. The diagnosis of this rare disease is based on clinical findings supported by positive blood culture. Recently, it has been shown that optical coherence tomography (OCT) characteristic findings are beneficial in making a correct diagnosis of fungal infection in cases with endogenous endophthalmitis. The current photo-essay aims to highlight the role of OCT in diagnosis of Candida endogenous endophthalmitis where OCT imaging of one of the retinal lesions disclosed a pre-retinal hyper reflective lesion with overlying punctate vitreous opacities. We propose “inverted snowing-cloud” sign for this OCT pattern considering the resemblance of the vitreous opacities to snowflakes.

We performed a comprehensive search of the published literature in PubMed and Google Scholar to identify types, prevalence, etiology, clinical impact, and current methods for correction of various artifacts in optical coherence tomography angiography (OCTA) images. We found that the prevalence of OCTA image artifacts is fairly high. Artifacts associated with eye motion, misidentification of retinal layers, projections, and low optical coherence tomography signal are the most prevalent types. Artifacts in OCTA images are the major limitations of this diagnostic modality in clinical practice and identification of these artifacts and measures to mitigate them are essential for correct diagnosis and follow-up of patients.

Abstract The purpose of this study was to introduce a new deep learning (DL) model for segmentation of the fovea avascular zone (FAZ) in en face optical coherence tomography angiography (OCTA) and compare the results with those of the device’s built-in software and manual measurements in healthy subjects and diabetic patients. In this retrospective study, FAZ borders were delineated in the inner retinal slab of 3 × 3 enface OCTA images of 131 eyes of 88 diabetic patients and 32 eyes of 18 healthy subjects. To train a deep convolutional neural network (CNN) model, 126 enface OCTA images (104 eyes with diabetic retinopathy and 22 normal eyes) were used as training/validation dataset. Then, the accuracy of the model was evaluated using a dataset consisting of OCTA images of 10 normal eyes and 27 eyes with diabetic retinopathy. The CNN model was based on Detectron2, an open-source modular object detection library. In addition, automated FAZ measurements were conducted using the device’s built-in commercial software, and manual FAZ delineation was performed using ImageJ software. Bland–Altman analysis was used to show 95% limit of agreement (95% LoA) between different methods. The mean dice similarity coefficient of the DL model was 0.94 ± 0.04 in the testing dataset. There was excellent agreement between automated, DL model and manual measurements of FAZ in healthy subjects (95% LoA of − 0.005 to 0.026 mm2 between automated and manual measurement and 0.000 to 0.009 mm2 between DL and manual FAZ area). In diabetic eyes, the agreement between DL and manual measurements was excellent (95% LoA of − 0.063 to 0.095), however, there was a poor agreement between the automated and manual method (95% LoA of − 0.186 to 0.331). The presence of diabetic macular edema and intraretinal cysts at the fovea were associated with erroneous FAZ measurements by the device’s built-in software. In conclusion, the DL model showed an excellent accuracy in detection of FAZ border in enfaces OCTA images of both diabetic patients and healthy subjects. The DL and manual measurements outperformed the automated measurements of the built-in software.

Purpose: To compare the area of the foveal avascular zone (FAZ) in the superficial and deep retinal layers using two different spectral-domain optical coherence tomography angiography (OCTA) devices. Methods: A cross-sectional comparative study was conducted to obtain macular OCTA images from healthy subjects using Optovue RTVue XR Avanti (Optovue, Inc, Fremont, CA) and Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany). Two independent trained graders measured the FAZ area using automated slab segmentation. The FAZ area in the superficial and deep retinal layers were compared. Results: Twenty-three eyes of 23 subjects were included. The graders agreement was excellent ( > 0.86) for all measurements. The mean FAZ area was significantly larger at the superficial retinal layer as compared to the deep retinal layer on both devices (0.31 ± 0.08 mm 2 vs 0.26 ± 0.08 mm 2 in Optovue and 0.55 ± 0.16 mm 2 vs 0.36 ± 0.13 mm 2 in Spectralis, both P < 0.001). The mean FAZ area was significantly greater in the superficial and deep retinal layers using Spectralis as compared to Optovue measurements (P < 0.001 for both comparisons). Conclusion: In contrast to previous reports, the FAZ area was larger in the superficial retina as compared to deep retinal layers using updated software versions. Measurements from different devices cannot be used interchangeably.

Submacular perfluorocarbon liquid (PFCL) retention is a well-known complication of vitreoretinal surgeries; however, the optimal surgical technique for the removal of subfoveal PFCL is yet to be determined. We describe a novel surgical technique for the removal of retained submacular PFCL by performing a retinotomy adjacent to the inferotemporal arcade using a 41-gauge extendible subretinal injection needle and inducing a therapeutic retinal detachment. Through the same retinotomy, the bent 41-gauge needle was advanced into the subretinal space to reach the PFCL bubble. Subsequently, active aspiration of PFCL was performed. The surgical procedure was successfully performed in two patients. This technique appears to be an effective surgical approach for removing retained submacular PFCL bubble.

Aim: To determine the minimum number of optical coherence tomography B-scan corrections required to provide acceptable vessel density measurements on optical coherence tomography angiography images in eyes with diabetic macular edema. Methods: In this prospective, noninterventional case series, the optical coherence tomography angiography images of eyes with center-involving diabetic macular edema were assessed. Optical coherence tomography angiography imaging was performed using RTVue Avanti spectral-domain optical coherence tomography system with the AngioVue software (V.2017.1.0.151; Optovue, Fremont, CA, USA). Segmentation error was recorded and manually corrected in the inner retinal layers in the central foveal, 100th and 200th optical coherence tomography B-scans. The segmentation error correction was then continued until all optical coherence tomography B-scans in whole en face image were corrected. At each step, the manual correction of each optical coherence tomography B-scan was propagated to whole image. The vessel density and retinal thickness were recorded at baseline and after each optical coherence tomography B-scan correction. Results: A total of 36 eyes of 26 patients were included. To achieve full segmentation error correction in whole en face image, an average of 1.72 ± 1.81 and 5.57 ± 3.87 B-scans was corrected in inner plexiform layer and outer plexiform layer, respectively. The change in the vessel density measurements after complete segmentation error correction was statistically significant after inner plexiform layer correction. However, no statistically significant change in vessel density was found after manual correction of the outer plexiform layer. The vessel density measurements were statistically significantly different after single central foveal B-scan correction of inner plexiform layer compared with the baseline measurements ( p = 0.03); however, it remained unchanged after further segmentation corrections of inner plexiform layer. Conclusion: Multiple optical coherence tomography B-scans should be manually corrected to address segmentation error in whole images of en face optical coherence tomography angiography in eyes with diabetic macular edema. Correction of central foveal B-scan provides the most significant change in vessel density measurements in eyes with diabetic macular edema.

Purpose: To evaluate the correlation of the visual acuity and diabetic retinopathy stage using optical coherence tomography and optical coherence tomography angiography metrics. Methods: In this prospective study, optical coherence tomography and optical coherence tomography angiography images of patients with different stages of diabetic retinopathy were obtained. In optical coherence tomography angiography images, the size of foveal avascular zone, central macular thickness, and vessel density at superficial and deep capillary layers of the macula were measured. In optical coherence tomography images, the presence of intraretinal cyst, disorganization of retinal inner layer, and ellipsoid zone and external limiting membrane disruption were evaluated. The associations between the variables with visual acuity and diabetic retinopathy stage were analyzed. Results: In total, 68 eyes of 38 patients with a mean age of 58.96 ± 10.59 years were included. In total, 34 eyes were categorized as non-proliferative diabetic retinopathy, 14 as active, and 20 as regressed proliferative diabetic retinopathy. Univariate analysis showed deep parafoveal vessel density, central macular thickness, ellipsoid zone disruption, disorganization of retinal inner layer, and external limiting membrane disruption had a significant relationship with visual acuity. However, in multivariate analysis, only central macular thickness and ellipsoid zone disruption had significant association with visual acuity ( p = 0.02 and p = 0.01, respectively). There was a significant difference in deep parafoveal vessel density ( p = 0.04), but not in foveal avascular zone area, between different stages of diabetic retinopathy. Conclusion: In this study, the foveal avascular zone area did not correlate with visual acuity and different stages of diabetic retinopathy. Structural abnormalities on optical coherence tomography images with especial focus on outer retinal disruption provided more reliable predictors for visual acuity outcomes in patients with diabetic retinopathy.

Optical coherence tomography angiography (OCTA) is a novel non-invasive imaging modality for 3-dimensional visualization of retinal and optic nerve capillary networks. In this article, a comprehensive review of relevant original articles in the PubMed database was performed using the search terms “diabetic retinopathy,” “diabetic macular edema,” “diabetes mellitus,” and “optical coherence tomography angiography.” OCTA was found to detect microvascular changes early in diabetes mellitus, even before they become clinically evident. Morphological and qualitative assessment of vascular changes can help to determine the pathophysiological processes, activity, treatment, and follow-up of diabetic retinopathy (DR). Vessel density and foveal avascular zone are the most investigated quantified indices shown to be early predictors of DR, correlated to DR severity and visual function, and useful in predicting response to treatment. OCTA has shown to be a promising alternative to fluorescein angiography in the management of DR. Further studies are warranted to determine the role of OCTA in the routine clinical management of DR.

Purpose: To report the normal characteristics and correlations of the foveal microvascular networks using optical coherence tomography angiography (OCTA) in a healthy Iranian population. Methods: Enface 3x3 OCTA images were obtained using the RTVue Avanti spectral-domain optical coherence tomography with AngioVue software (Optovue, Fremont, CA, USA). Foveal avascular zone (FAZ) area, central foveal point thickness and inner retinal thickness at the foveal center and the vascular density of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in the fovea were recorded. Results: Seventy normal eyes of 70 subjects (range, 9 to 71 years) were studied. Mean FAZ area was 0.32 ± 0.11 (range, 0.13-0.67) mm2 in SCP and 0.50 ± 0.13 (range, 0.19-0.94) mm2 in DCP. Mean SCP vessel density was 29.6 ± 4.7 (range, 16.3-40.3) % in the fovea. Mean DCP vessel density was 27.0 ± 5.9 (range, 15.0-45.2) % in the fovea. The FAZ area at SCP level was negatively correlated to the central subfield thickness (P < 0.001). The FAZ area at DCP level correlated negatively to the central subfield thickness and was significantly associated to age (both P < 0.001). The foveal SCP vessel density significantly correlated with foveal thickness and the foveal DCP vessel density correlated significantly with central foveal subfield thickness and was inversely related to age (all P < 0.05). Conclusion: In this study, central foveal subfield thickness was a major determinant of the FAZ size and foveal vessel density. Age was a determinant for FAZ area and whole image vessel density in DCP.

Purpose: To provide the clinical recommendations for the administration of intravitreal anti-vascular endothelial growth factor (VEGF) drugs especially bavacizumab for ocular vascular diseases including diabetic macular edema, neovascular age-related macular degeneration, myopic choroidal neovascularization, retinal vein occlusion and central serous chorioretinopathy. Methods: Twenty clinical questions were developed by the guideline technical committee. Relevant websites and databases were searched to find out the pertinent clinical practice guidelines to answer the questions. The technical committee provided possible answers (scenarios) according to the available evidences for each question. All scenarios along with their levels of evidence and the supported articles were sent to the experts for external review. If the experts did not agree on any of the scenarios for one particular clinical question, the technical committee reviewed all scenarios and their pertinent evidences and made the necessary decision. After that, the experts were asked to score them again. All confirmed scenarios were gathered as the final recommendations. Results: All the experts agreed on at least one of the scenarios. The technical committee extracted the agreed scenario for each clinical question as the final recommendation. Finally, 56 recommendations were developed for the procedure of intravitreal anti-VEGF injection and their applications in the management of ocular vascular diseases. Conclusion: The implementation of this guideline can standardize the management of the common ocular vascular diseases by intravitreal injection of anti-VEGF agents. It can lead to better policy-making and evidence-based clinical decision by ophthalmologists and optimal evidence based eye care for patients.

Purpose: To evaluate choroidal thickness in patients with non-ocular Behçet's disease (BD) using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods: In this retrospective observational comparative study, we collected OCT and clinical data from the charts of 4 patients (7 eyes) with BD who had been referred for a screening eye exam and had a normal ocular examination. Data from 9 healthy volunteers (17 eyes) were collected as age-matched controls. The choroid was manually segmented from volume OCT scans using custom Doheny Image Reading Center OCT grading software (3D-OCTOR). Main outcome measures were choroidal thickness and intensity were compared between eyes of patients with BD and those of healthy controls. Results: Eyes of patients with non-ocular BD had significantly thinner mean central subfield choroidal thickness (227.5 ± 56.93 versus 306.85 ± 17.85, P = 0.04) and central subfield choroidal volume (0.18 ± 0.04 vs 0.24 ± 0.02, P = 0.005). There was no significant difference in mean choroidal thickness in the whole ETDRS grid or in mean choroidal intensity in the central subfield and the whole ETDRS grid between eyes of patients with non-ocular BD and those of controls. Conclusion: This study demonstrates that BD may have subclinical manifestations in the choroid, resulting in thinning of the choroid relative to normal eyes, even without overt signs of ocular involvement. Keywords: Choroidal thickness, Behçet's disease, Spectral domain optical coherence tomography, Choroidal intensity, Choroidal reflectivity

Abstract Background To study the impact of image quality on quantitative measurements and the frequency of segmentation error with optical coherence tomography angiography (OCTA). Methods Seventeen eyes of 10 healthy individuals were included in this study. OCTA was performed using a swept-source device (Triton, Topcon). Each subject underwent three scanning sessions 1–2 min apart; the first two scans were obtained under standard conditions and for the third session, the image quality index was reduced using application of a topical ointment. En face OCTA images of the retinal vasculature were generated using the default segmentation for the superficial and deep retinal layer (SRL, DRL). Intraclass correlation coefficient (ICC) was used as a measure for repeatability. The frequency of segmentation error, motion artifact, banding artifact and projection artifact was also compared among the three sessions. Results The frequency of segmentation error, and motion artifact was statistically similar between high and low image quality sessions (P = 0.707, and P = 1 respectively). However, the frequency of projection and banding artifact was higher with a lower image quality. The vessel density in the SRL was highly repeatable in the high image quality sessions (ICC = 0.8), however, the repeatability was low, comparing the high and low image quality measurements (ICC = 0.3). In the DRL, the repeatability of the vessel density measurements was fair in the high quality sessions (ICC = 0.6 and ICC = 0.5, with and without automatic artifact removal, respectively) and poor comparing high and low image quality sessions (ICC = 0.3 and ICC = 0.06, with and without automatic artifact removal, respectively). Conclusions The frequency of artifacts is higher and the repeatability of the measurements is lower with lower image quality. The impact of image quality index should be always considered in OCTA based quantitative measurements.

Different diseases of the optic disc may be caused by or lead to abnormal vasculature at the optic nerve head. Optical coherence tomography angiography (OCTA) is a novel technology that provides high resolution mapping of the retinal and optic disc vessels. Recent studies have shown the ability of OCTA to visualize vascular abnormalities in different optic neuropathies. In addition, quantified OCTA measurements were found promising for differentiating optic neuropathies from healthy eyes.

Purpose: To evaluate the effect of spironolactone on chronic central serous chorioretinopathy (CSC). Methods: In this prospective interventional case series, patients with chronic cSc were treated with spironolactone (25 mg daily) for at least 6 weeks. If the subretinal fluid (SRF) had not completely resolved by this time, treatment was continued, and the dosage was increased to 25 mg twice daily. Primary outcome measure was the change in maximum SRF height at the final follow-up visit, as detected by optical coherence tomography. Secondary outcome measures were changes in best corrected visual acuity (BCVA) and central macular thickness (CMT). Results: Sixteen eyes of 14 patients with chronic cSc were enrolled. Mean follow-up time was 6.4 ± 4.3 months. Baseline BcVA was 0.54 ± 0.44 logarithm of the minimum angle of resolution (log MAR), which improved to 0.42 ± 0.43 log MAR at the final visit (P = 0.04). Mean cMT decreased from 282.69 ± 103.23 μm at baseline to 236.75 ± 90.10 μm at final visit (P = 0.11), and the mean of maximum SRF height decreased from 155.63 ± 95.27 μm at baseline to 77.19 ± 95.68 μm at the final visit (P = 0.04). SRF resolved completely in seven eyes (43.75%). Conclusion: In eyes with persistent SRF due to CSC, spironolactone therapy was associated with a statistically significant decrease in maximum SRF height, as well as an improvement in BCVA.

Purpose: To present an overview on ultra-wide-field imaging in diabetic retinopathy. Methods: A comprehensive search of the pubmed database was performed using the search terms of “ultra-wide-field imaging”, “ultra-wide-field fluorescein angiography” and “diabetic retinopathy”. The relevant original articles were reviewed. Results: New advances in ultra-wide-field imaging allow for precise measurements of the peripheral retinal lesions. A consistent finding amongst these articles was that ultra-wide-field imaging improved detection of peripheral lesion. There was discordance among the studies, however, on the correlation between peripheral diabetic lesions and diabetic macular edema. Conclusions: Visualization of the peripheral retina using ultra-wide-field imaging improves diagnosis and classification of diabetic retinopathy. Additional studies are needed to better define the association of peripheral diabetic lesions with diabetic macular edema.

Purpose: To review the current literature on ocular application of erythropoietin (EPO). Methods: A comprehensive search was performed on Pubmed and Scopus databases. All selected articles were reviewed thoroughly by the authors to review current applications of the EPO in ocular diseases. Results: Various aspects of administration of EPO for different ischemic, traumatic, vascular, and degenerative disorders have been explained. The articles are generally preclinical with few small studies reporting clinical outcomes. Conclusion: EPO has been used for the treatment of different ophthalmic conditions with promising results. Further studies are needed to elaborate the role of EPO in management of ocular diseases.

Purpose: To evaluate the outcomes of ruthenium-106 ( 106 Ru) brachytherapy in terms of radiation parameters in patients with thick uveal melanomas. Material and methods: Medical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm) uveal melanoma treated with 106 Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA), and treatment-related complications were assessed. Results: Fifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD). Mean radiation dose to tumor apex and to sclera were 71 (± 19.2) Gy and 1269 (± 168.2) Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14) Gy/h and 6.44 (± 1.50) Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9) mm decreased to 4.5 (± 1.6) mm, 3.4 (± 1.4) mm, and 3.0 (± 1.46) mm at 12, 24, and 48 months after brachytherapy (p = 0.03). Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8%) patients. Mean Log MAR (magnification requirement) visual acuity declined from 0.75 (± 0.63) to 0.94 (± 0.5) (p = 0.04). Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04). Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes. Conclusions : Thick uveal melanomas are amenable to 106 Ru brachytherapy with less than recommended apex radiation dose and dose rates.

Purpose: To report the outcomes of half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). Methods: A chart review of patients with chronic CSC who had received half-dose verteporfin PDT (3 mg/m2) was performed. The main outcome measures were resolution of subretinal fluid and best corrected visual acuity (BCVA). Results: Fifty-three eyes of 51 patients with mean age of 45.01 ± 8.9 years were studied. Three, 6 and 12 months after half-dose PDT, subretinal fluid was completely resolved in 51 eyes (96.2%). In 2 eyes (one patient), subretinal fluid decreased at 3 months but one year later, an increase in subretinal fluid was detected on optical coherence tomography (OCT) which completely resolved following additional PDT. Another patient with recurrence of subretinal fluid rejected further treatment. Mean baseline central subfield thickness was 385 ± 113.0 μm which was decreased to 235 ± 39.7, 247 ± 49.7, and 244 ± 49.52 μm after 3, 6 and 12 months, respectively (all P-values < 0.001). Mean BCVA was 0.33 ± 0.27 LogMAR before PDT and 0.11 ± 0.18, 0.11 ± 0.17, 0.17 ± 0.26 and 0.10 ± 0.23 LogMAR, 3, 6 and 12 months and at final visit (up to 60 months) after PDT, respectively (all P-values < 0.001). Improvement ≥2 lines in BCVA occurred in 20 eyes (37.7%). Statistically significant correlations were found between improvement in BCVA and baseline BCVA, baseline central subfield thickness and central subfield thickness after resorption of subretinal fluid (P < 0.001, P= 0.04 and P= 0.01, respectively). No complications attributed to PDT were observed. Conclusion: Half-dose PDT is effective for treatment of patients with chronic CSC.

Purpose: To customize clinical practice guidelines (CPGs) for management of diabetic retinopathy (DR) in the Iranian population. Methods: Three DR CPGs (The Royal College of Ophthalmologists 2013, American Academy of Ophthalmology [Preferred Practice Pattern 2012], and Australian Diabetes Society 2008) were selected from the literature using the AGREE tool. Clinical questions were designed and summarized into four tables by the customization team. The components of the clinical questions along with pertinent recommendations extracted from the above-mentioned CPGs; details of the supporting articles and their levels of evidence; clinical recommendations considering clinical benefits, cost and side effects; and revised recommendations based on customization capability (applicability, acceptability, external validity) were recorded in 4 tables, respectively. Customized recommendations were sent to the faculty members of all universities across the country to score the recommendations from 1 to 9. Results: Agreed recommendations were accepted as the final recommendations while the non-agreed ones were approved after revision. Eventually, 29 customized recommendations under three major categories consisting of screening, diagnosis and treatment of DR were developed along with their sources and levels of evidence. Conclusion: This customized CPGs for management of DR can be used to standardize the referral pathway, diagnosis and treatment of patients with diabetic retinopathy.

Background: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population. Methods: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Results: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. Conclusions: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population

Purpose: To evaluate the frequency of behavioral disorders in children with significant refractive error and to compare the results with those of emmetropic children. Methods: In this prospective, comparative study from January to September 2013, refractive errors of all 5–12-year-old children who referred to a general eye clinic were recorded. A validated Persian version of the Rutter A scale was filled out by the parents for the evaluation of the child's behavioral disorders. The Rutter A scale scores of children with significant refractive error were compared with those of emmetropic eyes. Student t test, Chi square test, and Fisher's exact test were used for analysis. Differences with a P value less than 0.05 were considered significant. Results: One hundred eighty-three patients, including 101 patients with significant refractive error and 82 emmetropic subjects, were studied. Overall, 44 patients (24%) had behavioral disorders, according to the Rutter A scale scores. Thirty patients (29.7%) with significant refractive error and 14 emmetropic subjects (16.9%) had behavioral disorders (P = 0.043). The prevalence of behavioral disorders were 37.5% in hyperopia, 35.7% in hyperopia-astigmatism, 21.4% in simple astigmatism, 16.7% in myopia-astigmatism, and 14.3% in myopia. Compared with emmetropic subjects, the prevalence of behavioral disorders was statistically significantly higher only in patients with hyperopia and hyperopia-astigmatism (P = 0.019 and P = 0.040). Conclusion: The prevalence of behavioral disorders is higher in children with hyperopia and hyperopia-astigmatism.

Purpose: To evaluate the macular thickness changes in diabetic macular edema after meal. Methods: In this prospective case series, macular thicknesses of diabetic patients with clinically significant macular edema (CSME) were measured after 7 h of fasting and repeated 2 h after breakfast. Results: Thirty six eyes of 20 diabetic patients were evaluated. The mean central subfield thickness (CST) and maximum retinal thickness (MRT) significantly decreased after meal (mean change of −10.3 ± 14.3 μm and −13.1 ± 12.7 μm, respectively, both P

Background: We aimed here to investigate the association between alleles and genotypes of APOE and Age-related macular degeneration (AMD) development. Materials and Methods: After ophthalmological examination, 120 patients with confirmed AMD and 120 healthy controls were enrolled in the study. The polymorphic segment of APOE gene was PCR-amplified and sequenced to determine the frequency distribution of polymorphic alleles and genotypes of this gene in the sample population. Results: The frequency distribution of APOE alleles and genotypes differed significantly between the patients and the control groups (P

Purpose: We describe a patient with endogenous endophthalmitis caused by Acinetobacter spp. as the first clinical presentation of diabetes mellitus. Method: A 48-year-old otherwise healthy woman was referred with signs and symptoms of acute endophthalmitis in the left eye. Systemic work-up, vitreous tap, and intravitreal antibiotic injection were performed followed by pars plana vitrectomy. Results: The laboratory tests confirmed the diagnosis of diabetes mellitus. Vitreous culture was positive for Acinetobacter spp., and the organism was sensitive to colistin. One month after surgery, vision was no light perception, and the eye was phthisical. Conclusion: Diagnostic work-up should be performed even in otherwise healthy patients with endogenous endophthalmitis.

Purpose: To determine the frequency of complement factor H (Y402H) and age related macular degeneration susceptibility gene 2 (A69S) single nucleotide polymorphisms in patients with age-related macular degeneration (AMD) and in matched non-AMD controls in an Iranian population. Methods: Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association of Y402H and A69S polymorphisms with AMD were determined. Results: The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2) and 2.2 (95%CI, 1.6-3.1), respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Conclusion: Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population.

Purpose: To report a case of perfluorocarbon liquid (PFCL) migration into the subarachnoid space at the time of vitreoretinal surgery in a patient with morning glory syndrome associated retinal detachment. Case report: A 9-year-old girl underwent pars plana vitrectomy and silicone oil injection for retinal detachment associated with morning glory syndrome. PFCL was used for retinal stabilization before endolaser photocoagulation. The retina detached, and repeated vitrectomy and silicone oil injection was performed. Postoperative magnetic resonance imaging revealed PFCL in the subarachnoid space. Conclusion: The migration of perfluorocarbon into the subarachnoid space is a rare complication of vitrectomy in patients with morning glory syndrome.

Purpose: To report the outcomes of transscleral diode laser photocoagulation for treatment of type 1 prethreshold retinopathy of prematurity (ROP). Methods: In this prospective interventional case series, 139 eyes of 73 infants with type 1 prethreshold ROP underwent transscleral diode laser photocoagulation of the avascular retina under topical anesthesia without making a conjunctival incision. Supplemental transpupillary diode laser photocoagulation was used for zone 1 ROP in one eye. All patients were followed for 6 months. Main outcome measures were regression of ROP, incidence of unfavorable outcomes and adverse effects. Results: At the end of follow-up, neovascularization regressed completely in all eyes and no eye developed an unfavorable outcome. Repeated laser therapy was performed employing the same technique in 3 eyes (2.3%). Ocular adverse effects were minor including mild conjunctival injection and edema in all patients, small conjunctival lacerations in 12 eyes (8.7%), minor self-limited vitreous hemorrhage in 2 eyes (1.4%) and mild self-limited hyphema in one eye (0.7%). Conclusion: Transscleral diode laser photocoagulation is a safe and effective treatment option for type 1 prethreshold ROP. This technique can be performed under topical anesthesia.

Purpose: To report the outcomes of pars plana vitrectomy (PPV) and intravitreal phacoemulsification in patients with dropped nuclei/nuclear fragments following complicated cataract surgery. Methods: In this retrospective case series, charts of patients who had undergone PPV and intravitreal phacoemulsification for removal of dislocated nuclei/lens fragments were reviewed. After standard PPV, a conventional phacoemulsification probe with an amputated sleeve was used for grasping and emulsifying the nucleus/nuclear fragments in mid/anterior vitreous cavity. Pre- and postoperative visual acuity, and intra- and postoperative complications were recorded. Results: A total of 22 patients with mean age of 71.1΁8.2 years were studied. Mean interval between complicated cataract surgery and PPV was 26.6΁36.5 (range: 0-120) days. Patients were followed for a mean of 105.5΁57.5 days. Preoperatively, best corrected visual acuity was 2.4΁0.6 logMAR which was improved to 1.4΁0.6 logMAR at final follow-up (P

Cystoid macular edema (CME) is a major cause of decreased vision after complicated or uncomplicated cataract surgery. This paper reviews the use of intravitreal bevacizumab (IVB) injection for treatment of pseudophakic CME. In a literature search of all articles available on Medline and Scopus databases, 11 studies including one prospective and 4 retrospective studies, 4 case reports, one letter to editor and one review article were identified. All articles except one, reported the use of IVB for chronic CME unresponsive to at least one conventional treatment modality. The level of evidence for all studies was categorized as low or very low. Although intravitreal bevacizumab might be effective for many cases of pseudophakic CME, its use should be reserved for eyes unresponsive to conventional treatment modalities.

Vitrectomy and endoresection is an alternative to enucleation for the treatment of large malignant choroidal melanoma. We report a rare case of extensive recurrence of choroidal malignant melanoma with extraocular extension 11 years after surgical endoresection without adjuvant treatment.

PURPOSE: To determine normal values of standard full-field electroretinography (ERG) and to evaluate their variations with age in an Iranian population. METHODS: Through convenient sampling, 170 normal subjects 1-80 years of age were selected from residents of Tehran. ERG amplitudes and implicit time values were measured according to recommendations by the International Society for Clinical Electrophysiology of Vision. Evaluations consisted of light-adapted ERG including single-white flash and 30-Hz flicker response; and dark-adapted ERG including rod, maximal dark-adapted and cone responses. RESULTS: No significant difference in ERG values was observed between men and women, or between right and left eyes. ERG amplitudes were lower (P=0.04) and implicit time values were greater (P=0.03) in subjects 70-80 years of age as compared to younger individuals. CONCLUSIONS: ERG parameters are significantly diminished with age. Our results may serve as a reference against which standard ERG responses can be compared.

PURPOSE: To investigate central corneal thickness (CCT), endothelial cell characteristics and intraocular pressure (IOP) in eyes with prior pediatric cataract surgery and to compare them with eyes of normal age and sex matched controls. METHODS: Specular microscopy CCT and IOP measurements were performed in 31 eyes of 17 patients with prior congenital cataract extraction and 40 eyes of 20 age and sex matched subjects. The mean of three pachymetric and specular microscopic measurements were recorded. IOP was measured using Goldmann applanation tonometry. RESULTS: Mean CCT was 632±45 µm in eyes with prior pediatric cataract surgery vs 546±33 µm in control eyes (P < 0.001, independent t test and Mann Whitney U-test). Mean IOP was 22.1±3.9 mmHg in eyes with prior pediatric cataract surgery and 14.0±1.6 mmHg in the control group (P < 0.001, independent t-test). There was no significant difference between the two groups in cell count, polymegethism and mean cell area of corneal endothelial cells. CONCLUSIONS: Although the corneas were clinically clear and there was no significant difference in endothelial characteristics in eyes with prior pediatric cataract surgery as compared to normal controls, central corneal thickness in the operated eyes was significantly greater. To differentiate actual glaucoma from artifactual IOP increase, CCT measurement should be performed in these patients.

PURPOSE: To describe the association between vitreous traction on the optic disc and nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: Eighty three eyes of 83 patients with NAION were evaluated by optical coherence tomography (OCT) for detecting vitreous adhesion to the optic nerve head with separation from the adjacent retina (partial posterior vitreous detachment). Eyes which were negative for such adhesion underwent ultrasonography to detect complete posterior vitreous detachment (PVD). RESULTS: Fifty male and 33 female subjects with mean age of 51.9±10 years were studied. Partial PVD with optic nerve head adhesion was found in 54 patients (65.1%) using OCT. Ultrasonography detected complete PVD in all other eyes with optically empty spaces on OCT. CONCLUSION: Vitreous traction on the optic nerve head from partial PVD may play a causative role in some cases of NAION. This traction may impair vascular supply and/or axoplasmic flow leading to signs and symptoms of NAION.