Automated machine learning-based classification of proliferative and non-proliferative diabetic retinopathy using optical coherence tomography angiography vascular density maps.

PURPOSE: The study aims to classify the eyes with proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) based on the optical coherence tomography angiography (OCTA) vascular density maps using a supervised machine learning algorithm. METHODS: OCTA vascular density maps (at superficial capillary plexus (SCP), deep capillary plexus (DCP), and total retina (R) levels) of 148 eyes from 78 patients with diabetic retinopathy (45 PDR and 103 NPDR) was used to classify the images to NPDR and PDR groups based on a supervised machine learning algorithm known as the support vector machine (SVM) classifier optimized by a genetic evolutionary algorithm. RESULTS: The implemented algorithm in three different models reached up to 85% accuracy in classifying PDR and NPDR in all three levels of vascular density maps. The deep retinal layer vascular density map demonstrated the best performance with a 90% accuracy in discriminating between PDR and NPDR. CONCLUSIONS: The current study on a limited number of patients with diabetic retinopathy demonstrated that a supervised machine learning-based method known as SVM can be used to differentiate PDR and NPDR patients using OCTA vascular density maps.

Effect of panretinal photocoagulation on macular vasculature using optical coherence tomography angiography.

BACKGROUND: To evaluate the changes of macular vascular density in the superficial capillary (SCP) and the deep capillary plexus (DCP), foveal avascular area (FAZ), choroidal flow, and macular thickness after pan-retinal photocoagulation (PRP). METHODS: In this prospective interventional non-comparative case series, patients with very severe nonproliferative (NPDR) and early proliferative diabetic retinopathy (PDR) and no significant macular edema who were candidates for pan-retinal photocoagulation underwent measurement of corrected distance visual acuity (CDVA), optical coherence tomography (OCT), Optical coherence tomography angiography (OCTA) at the baseline, 1, and 6 months following completion of PRP treatment. RESULTS: Thirty-nine eyes from 21 patients with diabetes were enrolled. Superficial and deep capillary plexus densities in the foveal and parafoveal area didn't change significantly 1 and 6 months post-PRP (p > 0.1 in all of them). The FAZ area constricted 6 months following PRP (p = 0.075). Based on the calculated circularity index, the FAZ became significantly more circular after 6 months of follow-up (p = 0.047). Although the choroidal flow area increased after PRP this increase wasn't statically significant neither at 1 month nor at 6 months post-PRP (p = 0.31 and 0.23, respectively). CONCLUSION: Although OCTA parameters were not significantly affected by PRP at both short-term (1 month) and long-term (6 months) follow-ups, the FAZ area became significantly circular after PRP may be due to redistribution of blood flow in hypoperfused foveal capillary plexus.

Erratum: Retinal image mosaicking using scale-invariant feature transformation feature descriptors and Voronoi diagram (Erratum).

[This corrects the article DOI: 10.1117/1.JMI.7.4.044001.].

Retinal image mosaicking using scale-invariant feature transformation feature descriptors and Voronoi diagram.

Purpose: Peripheral retinal lesions substantially increase the risk of diabetic retinopathy and retinopathy of prematurity. The peripheral changes can be visualized in wide field imaging, which is obtained by combining multiple images with an overlapping field of view using mosaicking methods. However, a robust and accurate registration of mosaicking techniques for normal angle fundus cameras is still a challenge due to the random selection of matching points and execution time. We propose a method of retinal image mosaicking based on scale-invariant feature transformation (SIFT) feature descriptor and Voronoi diagram. Approach: In our method, the SIFT algorithm is used to describe local features in the input images. Then the input images are subdivided into regions based on the Voronoi method. Each pair of Voronoi regions is matched by the method zero mean normalized cross correlation. After matching, the retinal images are mapped into the same coordinate system to form a mosaic image. The success rate and the mean registration error (RE) of our method were compared with those of other state-of-the-art methods for the P category of the fundus image registration database. Results: Experimental results show that the proposed method accurately registered 42% of retinal image pairs with a mean RE of 3.040 pixels, while a lower success rate was observed in the other four state-of-the-art retinal image registration methods GDB-ICP (33%), Harris-PIIFD (0%), HM-2016 (0%), and HM-2017 (2%). Conclusions: The proposed method outperforms state-of-the-art methods in terms of quality and running time and reduces the computational complexity.

Intravitreal Ziv-Aflibercept in Patients With Diabetic Macular Edema Refractory to Intravitreal Bevacizumab.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of intravitreal ziv-aflibercept (IVZ) in patients with diabetic macular edema (DME) resistant to intravitreal bevacizumab (IVB). PATIENTS AND METHODS: This prospective study was conducted in patients with persistent DME. Patients were switched to IVZ no longer than 6 weeks after the last three consecutive monthly IVB treatments and monitored over a course of 12 weeks. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and macular volume on optical coherence tomography were compared. RESULTS: A total of 59 eyes (38 patients) were included. Mean BCVA improved from 0.84 to 0.71 logMAR (P = .001) after first IVZ treatment and remained significant. In a subgroup analysis, this significance was observed only in the group with baseline visual acuity of less than 20/50. Mean CMT decreased from 479 µm to 364 µm (P = .004) after the first IVZ injections and remained significant. CONCLUSION: IVZ may be best reserved for patients with persistent DME after initial failure with bevacizumab, with less likelihood for anatomic or functional improvement in those with mild persistent DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:145-151.].

Multifocal electroretinogram in diabetic macular edema and its correlation with different optical coherence tomography features.

PURPOSE: To evaluate multifocal electroretinogram (mfERG) parameters in eyes with diabetic macular edema (DME) and its correlation with vision and optical coherence tomography (OCT) features. METHODS: Fifty-four eyes of 27 subjects with DME due to nonproliferative diabetic retinopathy were evaluated. MfERG responses were measured in three concentric rings. Macular thickness was measured by OCT in each segment of the three concentric rings, and mfERG rings were superimposed on the macular thickness map. The correlation between macular thickness in specific points of the thickness map and changes of the mfERG parameters in the corresponding points of the mfERG field map was evaluated and the relationship between the OCT and mfERG changes and changes of best-corrected visual acuity (BCVA) was investigated. The central foveal B-scans of SD-OCT were used to evaluate any correlation between the external limiting membrane (ELM) status, ellipsoid zone (EZ) status, presence of cysts or disorganization of retinal inner layers (DRIL), and mfERG parameters at the central corresponding area. RESULTS: The mean of BCVA was 0.5 ± 0.3 in logMAR, and the central macular thickness was 392.6 ± 123.4 microns. The central ring P1 and N2 amplitudes had a significant correlation with BCVA in univariate and multivariate analyses (P = 0.001 for both, r = - 0.346 and r = - 0.646, respectively). There was a significant correlation between retinal thickness and the N1 amplitude in the central ring (P = 0.02, r = - 0.343). Outer retinal layer disruption (ELM and EZ) correlated with prolonged P1 implicit time at the corresponding location (P = 0.005, r = 0.068). The presence of the DRIL was associated with reduced P1 and N2 amplitudes (P = 0.037, r = - 0.284 and P = 0.019, r = - 0.562, respectively). A significant correlation was also found between the presence of cysts and a lower central P1 amplitude (P = 0.033, r = - 0.376). CONCLUSION: In diabetic patients, discrete changes of some parameters in the central ring of the mfERG field map (e.g., P1 and N2 amplitudes) have a significant correlation with both structural OCT abnormalities in the corresponding points of the thickness map (like DRIL, intraretinal cyst and ELM/EZ disruption) and BCVA. Predictive models such as those described in this report may make it possible to identify the relationship between specific anatomical and functional characteristics in diabetic retinopathy.

Prevalence and Risk Factors of Retinopathy of Prematurity in Iran.

PURPOSE: The present study aimed to evaluate the frequency and risk factors of retinopathy of prematurity (ROP) among Iranian infants. METHODS: A retrospective cohort study was conducted on infants who had undergone screening for ROP at Farabi Eye Hospital, between March 2016 and March 2017. Data were analyzed based on the presence of extreme prematurity (gestational age ≤ 28 weeks), extremely low-birth-weight ( ≤ 1000 g), and multiple-gestation (MG) infants. RESULTS: The prevalence of ROP was 27.28% ( n = 543) among all screened infants, 74.4% for extremely preterm (EP) infants, 77.5% for extremely low birth weight (ELBW) babies, and 27.25% for infants from MG pregnancies. On multivariate analysis, gestational age, birth weight, and history of transfusion ( P < 0.0001, P < 0.0001, and P = 0.04, respectively) were found to be significantly associated with ROP. More advanced stages of ROP ( P < 0.0001) were observed in EP and ELBW infants. Birth weight ( P = 0.088), history of transfusion ( P = 0.066), and intubation ( P = 0.053) were not associated with increased risk of ROP in EP infants, while gestational age ( P = 0.037) and history of transfusion ( P = 0.040) were significant risk factors for ROP in ELBW infants. Gestational age (P < 0.001) and birth weight ( P = 0.001) were significantly associated with ROP in infants from MG pregnancies in multivariate analysis. CONCLUSION: ROP remains a commonly encountered disease, especially in ELBW and EP infants. The history of transfusion may have a role in stratifying the risk for ROP and guiding future screening guidelines.

The Accuracy of Digital Imaging in Diagnosis of Retinopathy of Prematurity in Iran: A Pilot Study.

PURPOSE: To evaluate sensitivity and specificity of digital retinal image reading in the diagnosis of referral-warranted retinopathy of prematurity (ROP). METHODS: Infants referred to the ROP clinic underwent fundus examination through indirect ophthalmoscopy. Fundus photographs were acquired using RetCam (shuttle 2; Clarity medical systems, Pleasanton, CA, USA). Four retinal specialists who were blind to patients' information reviewed the RetCam fundus photographs. By comparing the results of photographs' readings with that of indirect ophthalmoscopy as the gold standard, the sensitivity and specificity of telescreening was determined. RESULTS: A total of 147 treatment-naïve patients met the inclusion criteria and were enrolled in the study. Mean gestational age (GA) was 28.6 ± 2.0 weeks. Digital retinal imaging had sensitivity of 85% and specificity of 35% in detecting referral-warranted ROP in our study. Positive predictive value of digital photography was 80%, and negative predictive value was 43%. CONCLUSION: Digital photography for diagnosis of ROP may show good potential as a screening modality in developing countries. It can facilitate early diagnosis, prevent unnecessary referrals, and be implemented for investigational purpose. However, the overall study result did not provide evidence to propose digital photography as a substitute for indirect ophthalmoscopy in the diagnosis of ROP.

Incidence and Risk Factors for Post-Intravitreal Injection Endophthalmitis in a Modified Operating Room Setting.

Purpose: To evaluate the incidence and risk factors of post-intravitreal injection (IVI) endophthalmitis in a single center modified operating room (OR) setting.Methods: In a retrospective chart review study, patients who underwent IVI in a modified OR between September 2014 and November 2016 were included. Cases of post-IVI endophthalmitis were identified from the Hospital Infection Control Committee records, which tracks all post-procedure infections.Results: 51 472 IVIs (37 814 patients) including 13 658 bilateral simultaneous injections were performed during the study period. There were 17 cases of endophthalmitis (0.033%, 95% CI 0.019%-0.052%). There were no cases of bilateral endophthalmitis. Age, sex, indication for IVI, simultaneous bilateral injections, number of previous injections, and type of injected drug were not significantly associated with incidence of endophthalmitis.Conclusion: Post-IVI endophthalmitis is rare in this modified OR setting. Simultaneous bilateral IVIs and on-site preparation of injections are safe under these conditions.

Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline.

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.

Efficacy of Intravitreal Bevacizumab for the Treatment of Zone I Type 1 Retinopathy of Prematurity.

PURPOSE: To describe the efficacy of intravitreal bevacizumab for the treatment of type 1 retinopathy of prematurity (ROP) in zone I. METHODS: Preterm infants with type 1 ROP in zone I (zone I ROP, any stage with plus disease or zone I ROP, stage 3 without plus disease) were enrolled in this prospective study. Intravitreal bevacizumab (0.625 mg/0.025 ml) was injected under topical anesthesia. Patients were followed weekly for 4 weeks and then biweekly till 90 weeks gestational age. RESULTS: Seventy eyes of 35 patients with type 1 ROP in zone I were enrolled. At a gestational age of 90 weeks, ROP regressed with complete or near-complete peripheral retinal vascularization, in 82.9% of eyes after a single injection and in 92.9% of eyes after up to two injections. In five eyes (7.1%), ROP progressed to stage 4B or 5, so surgical management was required. There were no major complications such as endophthalmitis, cataract, or vitreous hemorrhage after injection. CONCLUSION: Intravitreal bevacizumab injection is an effective method for the management of patients with Zone I ROP requiring treatment; however, some cases may progress to more advanced stages and require surgical management. Close monitoring for recurrence or progression is necessary. Eyes with persistent zone I ROP may progress to advanced stages when treated with intravitreal bevacizumab injection and re-treatment may be needed.

Intravitreal bevacizumab alone or combined with 1 mg triamcinolone in diabetic macular edema: a randomized clinical trial.

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal 1 mg triamcinolone acetonide (IVT) in center-involved diabetic macular edema. METHODS: In this randomized clinical trial study, ninety-two eyes of 46 patients with bilateral center-involved diabetic macular edema and no previous treatment were included in the study. One eye of each patient was randomly assigned to 1.25 mg of IVB injection or combination of 1.25 IVB and 1 mg IVT. Evaluation of best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP) and grading of lens opacity was conducted at baseline, and weeks 2, 4, 6, 8, 12 and 24 after treatment. Retreatment was performed at a 6-week interval whenever indicated based on CMT. RESULTS: Between the groups, BCVA changes were not statistically different until 24-week follow-up (P > 0.05), but at 24 weeks after treatment, BCVA improvement was significantly better in IVB group (P = 0.049). Significant CMT reduction was observed in each group along the follow-up period (P = 0.001). The mean CMT reduction was more significant in combination (IVB + IVT) group at 2 weeks of follow-up (P < 0.001), but CMT changes were not significant between the groups at weeks 12th and 24th after injection. Overall, retreatment was applied for 59 eyes up to 24 weeks (33 in the IVB group, 26 in the IVB + IVT group). Among patients with 2 or more injections, number of injections was significantly lower in IVB + IVT group (P = 0.043). Three eyes within IVB + IVT group developed IOP rise beyond 21 mmHg, which were controlled with topical anti-glaucoma medications within 1 week. Changes in lens opacity were not significant between two groups. CONCLUSION: Eyes treated with IVB plus 1 mg IVT injections had more significant reduction in CMT in early post-injection, but this effect was transient. Although after 24 weeks visual acuity improvement was better in IVB group, combination therapy may decrease the number of injections. Combining 1 mg of intravitreal triamcinolone with bevacizumab was not accompanied with significant side effects.

Fibrin gel as a scaffold for photoreceptor cells differentiation from conjunctiva mesenchymal stem cells in retina tissue engineering.

Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue. In this study fibrin gel was used as hydrogel scaffold for immobilization of cells. The structural characteristics of fibrin gel scaffold were examined with SEM. Rheological properties of fibrin gel were measured by rheometer and biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem cells CJMSCs, the cells were differentiated into photoreceptor-like cells by exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as photoreceptor-like cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM analysis showed CJMSCs were well attached in fibrin gels and there were good integrity between cells and scaffold. The elastic modulus and constant degradation of the gel contributes to the growth and proliferation of cells. There was no toxicity effect of fibrin hydrogel on cells and the viability of cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After 2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and RPE65 as special markers of photoreceptor cells were detected by Real time PCR and immunofluorescence that these expressions in 3 D groups were higher than TCP groups. In conclusion, our findings showed that application of readily available sources of adult stem cells like human conjunctiva stem cells encapsulated in fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell numbers for repair and regeneration of retina disease such as photoreceptor injury.

Comparison of Intravitreal Bevacizumab and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity.

PURPOSE: To compare the outcomes of patients with type I retinopathy of prematurity (ROP) treated with either intravitreal bevacizumab (IVB) or retinal laser photocoagulation (RLP). DESIGN: Retrospective case series. PARTICIPANTS: Infants treated for type I ROP with IVB or RLP. METHODS: Patients who were born between January 2011 and December 2014 and were treated in Farabi Eye Hospital were included. The outcomes were stratified and analyzed, based on the treatment type and ROP zone. MAIN OUTCOME MEASURES: Need for retreatment, time to regression, refractive errors, retinal adverse anatomic outcomes, and rate of complications. RESULTS: Five hundred twenty-three patients were treated for type 1 ROP, of whom 493 (986 eyes) met inclusion criteria. Seven hundred twenty-four eyes (73.4%) received IVB, and 262 eyes (26.5%) received RLP. Re-treatment (because of recurrent or persistent retinopathy) occurred in 14.4% (106/724) of eyes initially treated with IVB and in 8.8% (23/262) eyes initially treated with RLP (P = 0.065). Re-treatment was not significantly different between the 2 groups for patients with zone I disease (P = 0.978). Re-treatment rate was considerably higher in patients with zone II disease treated with IVB (69/558 [12.3%]) compared with those treated with RLP (20/251 [7.9%]; P = 0.017). In the IVB group, 82.8% and 53.4% of eyes showed an avascular area in zone III (despite ROP regression) at 1 and 2 years after treatment, respectively. The spherical power and the spherical equivalent were significantly higher in eyes treated with RLP (-1.31±2.83 diopters [D] and -2.84±2.77 D, respectively) than eyes treated with IVB (0.19±3.21 D and -1.26±3.19 D, respectively; P = 0.016 and P = 0.007, respectively). Differences in astigmatic power were not significant. CONCLUSIONS: Both IVB and RLP are effective treatments for type 1 ROP. Longer follow-up time is necessary for infants treated with IVB. More patients with zone II disease treated with RLP achieved disease regression after a single treatment than those who received IVB, although outcomes after re-treatment were comparable except for a greater refractive error in patients treated with RLP.

The Role of Mitochondria in AMD: Current Knowledge and Future Applications.

Mitochondria are organelles which comprise the main respiratory machinery in the eukaryotic cells. In addition to their crucial role in energy production, they have profound effects on apoptosis and retrograde signaling to nucleus. Mitochondria have their own DNA, which codes for different proteins mostly involved in oxidative phosphorylation. Significant changes in the mitochondria of retinal pigment epithelium have been reported in age-related macular degeneration (AMD), which is correlated with the severity of the disease. Cybrid cell lines that have identical nuclei but mitochondria from different individuals can provide a unique means for studying the relationship between mitochondria and AMD. Different approaches for protection of mitochondria have been introduced which can be considered as potential future treatments for AMD and other age- related disorders.

Retina tissue engineering by conjunctiva mesenchymal stem cells encapsulated in fibrin gel: Hypotheses on novel approach to retinal diseases treatment.

BACKGROUND: Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. PRESENTATION OF THE HYPOTHESIS: Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders. TESTING THE HYPOTHESIS: In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells. IMPLICATIONS OF THE HYPOTHESIS: Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration.

Effects of Benzo(e)pyrene on Reactive Oxygen/Nitrogen Species and Inflammatory Cytokines Induction in Human RPE Cells and Attenuation by Mitochondrial-involved Mechanism.

PURPOSE: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: ARPE-19 cells were treated for 24 hours with 200 µM, 100 µM, and 50 µM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay. Multiplex bead arrays were used to measure levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Transforming Growth Factor alpha (TGF-α) and Vascular Endothelial Growth Factor (VEGF). IL-6 levels were also measured by an enzyme-linked immunosorbent assay. Real-time qPCR analyses were performed with primers for C3 (component 3), CFH (inhibits complement activation), CD59 (inhibitor of the complement membrane attack complex (MAC)) and CD55/DAF (accelerates decay of target complement target proteins). RESULTS: The ARPE-19 cultures treated with B(e)p showed significantly increased ROS/RNS levels (P < 0.001), which were then partially reversed by 6 µM Antimycin A (19%, P = 0.03), but not affected by the other ROS/RNS inhibitors. The B(e)p treated cultures demonstrated increased levels of IL-6 (33%; P = 0.016) and GM-CSF (29%; P = 0.0001) compared to DMSO-equivalent controls, while the expression levels for components of the complement pathway (C3, CFH, CD59 and CD55/DAF) were not changed. CONCLUSION: The cytotoxic effects of B(e)p include elevated ROS/RNS levels along with pro-inflammatory IL-6 and GM-CSF proteins. Blocking the Qi site of cytochrome c reductase (complex III) with Antimycin A led to partial reduction in B(e)p induced ROS production. Our findings suggest that inhibitors for multiple pathways would be necessary to protect the retinal cells from B(e)p induced toxicity.

Diabetic Retinopathy Clinical Practice Guidelines: Customized for Iranian Population.

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.

Complement factor H and LOC387715/ARMS2/HTRA1 variant's frequencies and phenotypic associations in neovascular age-related macular degeneration, a pilot study.

PURPOSE: To evaluate the frequency of 12 single nucleotide polymorphisms (SNPs) of complement factor H (CFH) and LOC387715/ARMS2/HRTA1 and their association with some of the presenting clinical features of neovascular age-related macular degeneration (AMD). METHODS: In this prospective non-comparative case series forty four naïve patients with neovascular AMD were genotyped using sequencing or Sequenom iPLEX technology. Descriptive tests were used for displaying the magnitude of each allele, gender distribution, and age at diagnosis. Fisher exact test was used to evaluate the correlation between visual acuity (VA) and different alleles. Also Kruskal-Wallis test was used for comparison between age at the time of diagnosis and different alleles. RESULTS: The most frequent SNP among studied patients was rs1061147 with 100% frequency rate. The least common was rs2672598 with a frequency of 52.27%. Only the allele rs800292 of CFH locus on 1q32 was associated with VA better than 20/200 (p value = 0.034). The frequency of this allele was 77.27% (34 patients) in this study. There was no significant association between any of alleles, and VA worse than 20/200(p > 0.05). Fifteen patients had bilateral exudative AMD (34.09%). There was no significant difference between alleles in bilateral neovascular AMD and unilateral disease. Also bilateral and unilateral patients were not different in terms of age, gender or VA (p value: 0.330, 0.764 and 0.456 respectively). There was also no significant association between any of SNPs and bilaterality of disease. CONCLUSION: We designated the frequencies of SNPs of CFH and LOC387715/ARMS2/HRTA1 in neovascular AMD in a sample of Iranian patients. Only the allele rs800292 of CFH locus on chromosome 1q32 was associated with better VA.

CHOROIDAL THICKNESS CHANGES IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION VERSUS PANRETINAL PHOTOCOAGULATION WITH INTRAVITREAL BEVACIZUMAB.

PURPOSE: To compare choroidal thickness (CT) and retinal thickness (RT) between eyes with proliferative diabetic retinopathy treated with panretinal photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB). METHODS: Thirty-three patients with proliferative diabetic retinopathy were randomized to have one eye treated with PRP and the other with PRP + IVB. Change in CT was compared with baseline using enhanced depth imaging-optical coherence tomography at baseline and Months 1, 3, 6, and 10 after treatment. Change in RT was similarly assessed using spectral domain optical coherence tomography. Changes in both CT and RT were assessed in all nine macular areas as defined by Early Treatment Diabetic Retinopathy Study subfields. RESULTS: The PRP + IVB group had a significant decrease in subfoveal CT at 3 and 10 months (323.9 ± 62 µm at baseline vs. 320.7 ± 64.8 µm at Month 3 [P = 0.024] and 304.7 ± 65.6 µm at Month 10 [P = 0.003]). Subfoveal CT significantly decreased at 10 months compared with baseline in the PRP group (320.8 ± 57.7 at baseline to 297 ± 66.3 µm at 10 months, P = 0.01). Subfoveal CT was not significantly different between the 2 groups at 10 months. The best-corrected visual acuity did not change after treatment in the two groups, and there was no correlation between BCVA and CT changes (r = 0.222, P = 0.37 in the PRP group and r = 0.387, P = 0.12 in the PRP + IVB group). Significant increases in RT were seen in the PRP + IVB group at 6 months and in the PRP group at Months 1, 3, 6, and 10. A correlation between changes in CT and RT was only seen in the PRP group at 10 months after treatment. CONCLUSION: Eyes with proliferative diabetic retinopathy treated with PRP + IVB and PRP both had significant reduction in CT at 10 months; however, the eyes that were also treated with IVB also underwent an earlier but transient reduction at 3 months. Patients treated with IVB underwent less increase in RT.