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Background: Diabetic retinopathy (DR) is one of the most common causes of vision loss worldwide; however, the limited access of the majority of the population to ophthalmologists and the lack of awareness among patients highlight the important role of family physicians in diagnosing this problem. This study aimed to determine the accuracy of direct ophthalmoscopy for DR screening by family physicians. Method: In this cross-sectional study, 121 patients were examined by three groups of physicians using direct ophthalmoscopy. Each of the two first groups (A and B) consisted of four family physicians who received written instructions and educational software regarding DR diagnosis, with group A also receiving a 2-h in-person class. The third group included four ophthalmologists (O). Based on the severity of diagnosis, results were compared with standard diagnosis provided by a retina fellow student. Results: Sensitivity of groups A, B, and O was calculated as 59%, 51%, and 78%, respectively. The specificity of the groups was also measured as 75.6%, 86.5%, and 80.0%, respectively. The study groups did not demonstrate a significant difference in regard to diagnostic parameters (p > 0.05). An additional analysis was conducted, only focusing on the diagnosis of severe DR, where the specificity of all groups improved. Still, no significant difference was observed between groups (p > 0.05). Conclusion: This was the first study investigating the role of family physicians in DR screening in Iran. The results indicated that trained family physicians could be reliable enough for diagnosing DR with the help of a direct ophthalmoscope. They can be used as a part of a referral protocol in deprived areas where access to an ophthalmologist is difficult. [ABSTRACT FROM AUTHOR]

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of ischemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accompanying risk factors, the middle and inner retinal vasculature and blood flow, and the vulnerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resembles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible associations between the middle and inner retinal ischemic patterns. [ABSTRACT FROM AUTHOR]

To determine the optical coherence tomography angiography (OCTA) parameters including foveal avascular zone (FAZ) and vessel density (VD) in the amblyopic eyes compared with the fellow sound eyes and the eyes of the non-amblyopic subjects. In this case–control study, a total of 23 eyes from unilateral amblyopic children were included as cases. The sound eye of the amblyopic children was considered as the internal control and the right eyes of the non-amblyopic children were considered as the external control. All participants underwent image recording with OCTA. In the present study, an equal number of 23 unilateral amblyopic eyes and 23 right eyes of non-amblyopic age- and sex-matched children were included as the cases and controls, respectively. The average age of participants in the case and controls were 9.86 ± 3.12 and 8.5 ± 2.35 years, respectively. Twelve patients (52.2%) in the case group and 14 subjects (60.9%) in the control group were female. Whole vascular density of the macula in superficial capillary plexuses (SCP) was significantly lower in the external controls compared with the other studied groups (P =.026). However, the VD of the deep capillary plexuses (DCP) was significantly greater in the external controls than cases and internal controls (P=.029). The average FAZ area was 0.26 ± 0.06 mm2 in amblyopic eyes that was significantly higher compared with fellow eyes (0.21 ± 0.07 mm2; P=.022), but it was not different with non-amblyopic eyes (0.22 ± 0.118 mm2). Based on our findings, there were no significant difference in the cases of foveal, parafoveal, and perifoveal in both superficial and deep vascular densities among amblyopic and non-amblyopic eyes, whereas deep whole density of the amblyopic eyes showed lower percent compared to non-amblyopic ones that indicates decrease blood supply of the amblyopic eyes in this region. Additionally, FAZ was larger in amblyopic eyes than internal controls. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the retinal vascular response to hyperoxia in patients with diabetes at the preclinical stage of diabetic retinopathy (DR) and to quantify the changes in comparison with normal subjects using optical coherence tomography angiography (OCTA). Methods. In this prospective study, 40 eyes of 20 participants comprising 10 diabetic patients with no diabetic retinopathy (NDR) and 10 normal subjects were recruited. OCTA images were acquired in the resting position and were repeated after a hyperoxic challenge using a nasal mask connected to a reservoir bag supplying 100% oxygen at the rate of 15 L per minute for 5 minutes. The changes of mean parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the foveal avascular zone (FAZ) size, and the outer retina flow index were compared between two conditions in each group and between the two study groups. The statistical significance of differences in the means was evaluated using Student's t-test for unpaired samples with consideration of the generalized estimating equations (GEE) for intereye correlation. Results. At baseline, the mean parafoveal VD of SCP and DCP were significantly lower in the NDR participants compared to the healthy subjects (P < 0.001 and P = 0.006, respectively). After induction of the hyperoxic challenge in healthy participants, mean parafoveal VD reduced at both the SCP and DCP, but reached a statistical significance only in DCP (P = 0.006). However, following induction of hyperoxic challenge in patients with NDR, no significant decline was noticed in mean parafoveal VD of SCP and DCP. The degree of change in mean parafoveal VD of DCP was statistically significantly more pronounced in healthy subjects compared to the NDR group (P = 0.034). The change in FAZ size and the outer retina flow index were comparable between the two study groups. Conclusion. Retinal capillary layers responded differently to hyperoxia-induced challenge, and in normal subjects, the autoregulatory mechanism was mostly effective in the parafoveal DCP. Retinal vascular reactivity was impaired in SCP and DCP at the preclinical stage of DR. OCTA as a noninvasive modality was able to quantify the retinal vascular response to the hyperoxic challenge. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of repeated intra-silicone oil (SO) injections of methotrexate (MTX) on the outcomes of surgery for rhegmatogenous retinal detachment (RRD) with grade C proliferative vitreoretinopathy (PVR-C). Methods: In this prospective pilot case series, eyes with RRD and PVR-C underwent pars plana vitrectomy and intraocular injection of SO. At the conclusion of the procedure, 250 µg of MTX was injected into the SO-filled vitreous cavity. Intra-SO injection was repeated at weeks 3 and 6; the minimum follow-up period was 6 months. The main outcome measure was retinal reattachment rate. Results: Eleven eyes of 11 patients (mean age, 52.73 ± 18.01 years) were included. The mean follow-up period was 9 ± 3 months (range, 6–15 months). Total retinal detachment with anterior and/or posterior PVR-C was present in all eyes before surgery. Mean preoperative best-corrected visual acuity (BCVA) was 2.62 ± 0.04 logMAR. All operated eyes exhibited retinal reattachment posterior to the equator during the follow-up period. Mean postoperative BCVA was significantly improved to 1.02 ± 0.51 logMAR (p = 0.003). No ocular or systemic side effects were observed. Conclusion: Repeated intra-SO injection of MTX as an adjunctive therapy for RRD complicated by PVR showed promising results and was not associated with adverse effects. Further studies are needed to confirm its possible beneficial effects on the final anatomic and functional outcomes in these cases. [ABSTRACT FROM AUTHOR]

In this article, we propose a new U‐Net‐based approach for intraretinal cyst segmentation across different vendors that improve some of the challenges faced by previous deep‐based techniques. The proposed method has two main steps: (1) prior information embedding and input data adjustment, (2) the segmentation model. In the first step, we inject the information into the network in a way that overcomes some of the network limitations in receiving data and learning important contextual knowledge. And in the next step, we introduce a connection module between the encoder and decoder parts that transfers information more effectively from the encoder to the decoder. Two public datasets, namely, OPTIMA and KERMANY, are employed to evaluate the proposed method. The results show that the proposed method is an efficient vendor‐independent approach for the segmentation of intraretinal cystoid fluid with mean Dice values of 0.78 and 0.81 on the OPTIMA and KERMANY datasets, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Intra‐retinal cyst (IRC) is a symptom of macular disorders that occurs due to retinal blood vessel damage and fluid leakage to the macula area. These abnormalities are efficiently visualized using optical coherence tomography (OCT) imaging. These patients need to be regularly monitored for the presence and changes of IRC regions. Thus, automatic segmentation of IRCs can be beneficial to investigate disease progression. Methods: In this study, automatic IRC segmentation is accomplished by building three different masks in three unsupervised segmentation levels of a hierarchical framework. In the first level, the ROI‐mask (R‐mask) is built, and the retina area is cropped based on this mask. In the second level, the prune‐mask (P‐mask) is built, and the searching space is significantly reduced toward the target objects using this mask; and finally in the third level, by applying the Markov random field (MRF) model and employing intensity and contextual information, the cyst mask (C‐mask) is extracted. Results: The proposed method is evaluated on three datasets including OPTIMA, UMN, and KERMANY datasets. The experimental results showed that the proposed method is effective with a mean dice coefficient rate of 0.74, 0.75 and 0.79 by the intersection of ground truths on the OPTIMA, UMN and KERMANY datasets, respectively. Conclusion: The proposed method outperforms the state‐of‐the‐art methods on the OPTIMA and UMN datasets while achieving comparable results to the most recently proposed method on the KERMANY dataset. [ABSTRACT FROM AUTHOR]

Purpose: To present a classification of inherited retinal diseases (IRDs) and evaluate its content coverage in comparison with common standard terminology systems. Methods: In this comparative cross-sectional study, a panel of subject matter experts annotated a list of IRDs based on a comprehensive review of the literature. Then, they leveraged clinical terminologies from various reference sets including Unified Medical Language System (UMLS), Online Mendelian Inheritance in Man (OMIM), International Classification of Diseases (ICD-11), Systematized Nomenclature of Medicine (SNOMED-CT) and Orphanet Rare Disease Ontology (ORDO). Results: Initially, we generated a hierarchical classification of 62 IRD diagnosis concepts in six categories. Subsequently, the classification was extended to 164 IRD diagnoses after adding concepts from various standard terminologies. Finally, 158 concepts were selected to be classified into six categories and genetic subtypes of 412 cases were added to the related concepts. UMLS has the greatest content coverage of 90.51% followed respectively by SNOMED-CT (83.54%), ORDO (81.01%), OMIM (60.76%), and ICD-11 (60.13%). There were 53 IRD concepts (33.54%) that were covered by all five investigated systems. However, 2.53% of the IRD concepts in our classification were not covered by any of the standard terminologies. Conclusions: This comprehensive classification system was established to organize IRD diseases based on phenotypic and genotypic specifications. It could potentially be used for IRD clinical documentation purposes and could also be considered a preliminary step forward to developing a more robust standard ontology for IRDs or updating available standard terminologies. In comparison, the greatest content coverage of our proposed classification was related to the UMLS Metathesaurus. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the most complications of diabetes. It is a progressive disease leading to significant vision loss in the patients. Abnormal capillary nonperfusion (CNP) regions are one of the important characteristics of DR increasing with its progression. Therefore, automatic segmentation and quantification of abnormal CNP regions can be helpful to monitor the patient's treatment process. We propose an automatic method for segmentation of abnormal CNP regions on the superficial and deep capillary plexuses of optical coherence tomography angiography (OCTA) images using the marker-controlled watershed algorithm. The proposed method has three main steps. In the first step, original images are enhanced using the vesselness filter and then foreground and background marker images are computed. In the second step, abnormal CNP region candidates are segmented using the marker-controlled watershed algorithm, and in the third step, the candidates are modeled using an undirected weighted graph and finally, by applying merging and removing procedures correct abnormal CNP regions are identified. The proposed method was evaluated on a dataset with 36 normal and diabetic subjects using the ground truth obtained by two observers. The results show the proposed method outperformed some of the state-of-the-art methods on the superficial and deep capillary plexuses according to the most important metrics. [ABSTRACT FROM AUTHOR]

The article reports on a clinical trial which evaluates the effects of oral colchicine on the prevention of proliferative vitreoretinopathy (PVR) in eyes undergoing scleral buckling (SB). It states that the subjects of the study were patients with rhegmatogenous retinal detachment undergoing SB. The findings of the study reveal that oral colchicine had no significant effect on the prevention of retinal redetachment due to PVR.

This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measured, with mean deviation (MD) index of the VF test and peripapillary retinal nerve fiber layer thickness as secondary measures. There was a statistically significant improvement in the patients' BCVA 1 and 3 months following IVF; BCVA improved from 1.69 ± 0.55 logMAR at baseline to 0.98 ± 0.47 and 0.93 ± 0.51 logMAR at 1 and 3 months, respectively ( P = .004). The change in BCVA was not significant between month 1 and month 3 ( P = .22). Peripapillary retinal nerve fiber layer thickness decreased from 173.5 ± 29.28 µm in the baseline evaluation to 85.8 ± 8.8 µm at 1 month, and 62.9 ± 5.97 µm at 3 months ( P = .003). MD values changed from 24.60 ± 3.80 to 21.0 ± 6.10 and 20.5 ± 6.50 at 1 and 3 months, respectively ( P = .007 and .005, respectively). This pilot study suggests that IVF may be an effective treatment for patients with recent-onset NAION. Larger studies are required to establish the therapeutic role of fasudil for NAION. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence and associated factors of AMD in an Iranian population in 2014. Methods: In this population-based cross-sectional study, a total of 2975 Iranian residents (age: ≥50 years) from the urban and rural areas of Gilan province were included. The prevalence of different grades of AMD was determined using the International Age-Related Maculopathy Epidemiological Study Group grading system. Results: Of 2975 eligible individuals, 2587 (87.0%) subjects participated and 2275 (76.5%) subjects (62.6 ± 8.8 years old) had gradable fundus photographs. Age- and sex-standardized prevalence of early and late AMD based on the 2016 Iran census were 13.2% (95% confidence interval [CI], 10.6–16.2) and 0.7% (95% CI, 0.4–1.3), respectively. In multivariate analysis, each decade increase in age was associated with the adjusted odds of any (adjusted odds ratio [AOR] = 1.31, 95% CI, 1.09–1.56; P =.0031), early (AOR = 1.27, 95% CI, 1.06–1.53; P =.012) and late AMD (AOR = 2.39, 95% CI, 1.08–5.28; P =.031). Hyperopia was identified to be less frequent in late AMD (AOR = 0.20, 95% CI, 0.04–0.80; P =.024). No significant association was found between AMD and sex, smoking, outdoor working, diabetes, hypertension, pseudophakia, hyperlipidemia and myopia. Conclusion: Gilan Eye Study demonstrated the first estimate of age-specific AMD prevalence in Iran being compatible with other WHO regions. With the expected increase in the life expectancy and aging of Iranians, the number of people affected by AMD will be increasing in future. Healthcare policy makers should be advised to provide more efficient eye care services and preventive strategies in this regard. [ABSTRACT FROM AUTHOR]

Purpose. To model a community-based telescreening program for diabetic retinopathy (DR) in Iran and to implement a pilot project at the Iranian Diabetes Society (IDS) branch in a Tehran suburb. Methods. In this mixed model study, a web application called the "Iranian Retinopathy Teleophthalmology Screening (IRTOS)" was launched. The educational course for DR screening was established for general practitioners (GPs). Registered patients in IDS branch were recalled for fundus photography; images were transferred to the reading center via IRTOS to be graded by GPs, and patients were informed about the results via mobile messaging. All images were independently reviewed by a retina specialist as the gold standard. Patients who required further assessment were referred to an eye hospital. Results. Overall, 604 subjects with diabetes were screened; of these, 50% required referral. The sensitivity and specificity for diagnosis of any stage of DR by trained GPs were 82.8% and 86.2%, respectively, in comparison to the gold standard. The corresponding values for detecting any stage of diabetic macular edema (DME) were 63.5% and 96.6%, respectively. Conclusions. Telescreening was an effective method for detecting DR in a Tehran suburb. This screening model demonstrated its capacity for promoting diabetic eye care services at the national level. However, the sensitivity for detecting DME needs to be improved by modifying the referral pathway and promoting the skill of GPs. [ABSTRACT FROM AUTHOR]

Connective tissue growth factor (CTGF) is released by retinal pigment epithelial (RPE) cells and detectable in proliferative membranes (PrMs). This experimental study was performed to investigate the mRNA and protein levels of both CTGF and vascular endothelial growth factor A (VEGF-A) in a rabbit model of proliferative vitreoretinopathy (PVR). In addition, the effects of a single intravitreal injection of the safe dose of anti-CTGF or bevacizumab as monotherapy and in combination were evaluated. PVR was induced in the right eye of albino rabbits by intravitreal injection of cultured adult human RPE cells. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot analysis of CTGF and VEGF-A were performed on whole eye tissue in the PVR model versus controls at different time points. In the next step, the PVR models were assigned to five groups. The monotherapy groups received a single intravitreal injection of 0.1 ml of anti-CTGF 100 μg/ml (final concentration of 6.6 μg/ml in the vitreous) or 0.03 ml of 25 mg/ml bevacizumab. In the combined group, the abovementioned amounts of anti-CTGF and bevacizumab were injected intravitreally from separate sites in one session. No antibody injection was performed in the control group. Intravitreal injection of 0.1 ml of control IgG (1 mg/ml of isotype matched) antibody was performed in the placebo group. After 2 weeks, histologic evaluation including, trichrome staining for collagen, immunostaining by anti-alpha-smooth muscle actin for myofibroblasts, and anti-collagen type-1 antibody on paraffin embedded anterior-posterior sections was done. In addition, fundus photography was performed for clinically equivalent PVR staging. Twenty-four hours following PVR induction, CTGF mRNA and protein levels increased five- and- three-fold compared to controls, respectively (P < 0.001). VEGF-A mRNA and protein levels decreased significantly after 72 h of PVR induction compared to controls (P < 0.05). Means of PrM thickness and myofibroblast cell counts significantly decreased in the anti-CTGF group (P < 0.001 and P < 0.05, respectively). The mean area of collagen type-1 fibers of PrM in the mono- and combination therapy groups that received intravitreal anti-CTGF was significantly reduced (P < 0.001); in addition, mild PVR (stage-1 and 2) formation occurred in comparison with moderate to severe PVR (stage-4 and higher) in other groups. In conclusion, we found that intravitreal injection of CTGF neutralizing antibody resulted in a reduction in PrM thickness, collagen fibers and myofibroblast density in the PVR model. CTGF inhibition may represent a potential therapeutic target for PVR. • There was a significant increase in CTGF mRNA and protein levels following induction of PVR in our rabbit model. • Mean thickness of proliferative membranes (PrMs) was lower in anti-CTGF treated eyes as compared to control eyes. • Myofibroblast cells were decreased significantly in anti-CTGF treated eyes as compared to control eyes. • Intravitreal anti-CTGF more effectively decreased the mean area of collagen type-1 fibers inside PrMs compared to anti-VEGF. [ABSTRACT FROM AUTHOR]

The article focuses on the study on diabetic retinopathy conducted in patients aged 40 to 80 years old in Yazd, Iran. Mentioned is the utilization of the cross-sectional population-based survey as well as random multi-stage cluster sampling. Noted is the presentation of standardized prevalences among diabetic patients along with the severity of diabetic retinopathy.