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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.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.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.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.

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.

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.]

The purpose of this study is to evaluate the concentration of vascular endothelial growth factor (VEGF) in the vitreous humor of patients with primary rhegmatogenous retinal detachment (RRD). This is a prospective case control study. Eighteen patients with primary RRD without proliferative vitreoretinopathy C (PVR C) were enrolled as cases, and twenty-two non-diabetic retinopathy patients who were candidates for complete pars plana vitrectomy due to Macular Hole or Epiretinal Membrane were included as the control group. Undiluted vitreal samples were collected during the initiation of Pars Plana Vitrectomy (PPV) prior to any infusion into the posterior cavity. Vitreous samples were also collected from 21 fresh cadaveric globes. The vitreous concentration of VEGF was measured by enzyme-linked immunosorbent assay (ELISA) technique and compared between these two groups. The vitreal concentration of VEGF was 0.643 ± 0.088 ng/mL in the RRD group. Measured concentrations of VEGF in controls were 0.043 ± 0.104 ng/mL, and in cadaveric eyes they were 0.033 ± 0.058 ng/mL. The mean VEGF concentration in the RRD group was statistically higher than in the control group (p < 0.0001) and cadaveric eyes (p < 0.0001). Our study shows that vitreal VEGF concentrations significantly increase in patients with RRD.

Purpose To describe a case of bilateral multiple serous retinal detachments (SRD) following bone marrow transplantation (BMT), which showed bilateral response to a single unilateral intravitreal bevacizumab injection. Case report A 37-year-old man with acute myelogenous leukemia who had received bone marrow transplantation four months prior was referred to our clinic with the chief complaint of gradually decreasing vision in both eyes for three months. During the funduscopic examination, multiple serous retinal detachments (SRD) were observed bilaterally, and he was diagnosed with multiple foci of central serous chorioretinopathy (CSCR). He was advised to discontinue the steroid dosage, which did not make significant improvement, and he was treated with intravitreal bevacizumab injection in the more severely affected eye. One month later, significant improvement was noticed in both eyes. Conclusion Serous retinal detachment is a rare complication following BMT. Significant bilateral improvement after single unilateral intravitreal bevacizumab injection shows not only the possible role of increased level of vascular endothelial growth factor (VEGF) in this case, but also the systemic diffusion of the drug and effect on the contralateral eye following unilateral injection.

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-naive 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.

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R2 = 0.9861, p ˂ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery.

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.

Background: Endophthalmitis is a severe and sight-threatening complication of ocular surgery or ocular trauma. The identification of common types and causative organisms is essential for prevention and management. Objective: The current study describes the prevalence of various types of endophthalmitis and the causative microbiological spectrum of each type treated in the Tertiary Referral Center in Iran. Methods: All cases of endophthalmitis admitted to the Emergency Department of Farabi Eye hospital (Tehran, Iran) between July 2013 and December 2014 were included in this study. The patients’ demographic data, type of endophthalmitis, aqueous or vitreous culture results, and treatment methods were recorded. Results: From 108 presumed endophthalmitis cases, post-operative endophthalmitis (68.5%) was the most frequent type followed by post-traumatic (25%), bleb-associated (4.6%), and endogenous (1.9%) types. Streptococcus viridians (37.5%) was the most common isolated organism in post-operative cases. In post-traumatic endophthalmitis patients, the most frequent causative organism was Staphylococcus epidermidis (70%). Conclusion: Many studies from other countries have reported that S. epidermidis is the leading cause of endophthalmitis after either intraocular surgeries or open-globe injuries, but the current study has shown that S. viridians is the most common isolated organism in post-operative endophthalmitis.

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.

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, macular thickness and parapapillary flow after panretinal photocoagulation (PRP).Method: 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 panretinal photocoagulation underwent measurement of corrected distance visual acuity (CDVA), optical coherence tomography (OCT), Optical coherence tomography angiography (OCTA) at the baseline (1–5 days before PRP), 1, and 5 to 7 months following completion of PRP treatment.Results: Thirty-nine eyes from 21 patients with diabetes were enrolled. foveal SCP (P > 0.1), foveal DCP (P > 0.1), parafoveal SCP (P > 0.1), and parafoveal DCP (P > 0.1) did not change 1 month and 6 months after PRP. The parafoveal inner retina thick slab density was significantly decreased at 6 months after PRP (p=0.015). Deep FAZ area constricted 6 months following PRP (P = 0.075). Based on calculated circularity index, the FAZ area became significantly more circular. (P=0.047). One month after PRP the inside disc vascular density was significantly increased from baseline (p=0.041); while, it was decreased to lower than baseline amount, 6 months after PRP .Conclusion: Although OCTA parameters were not significantly affected by PRP at both short- (1-month) long-term (6-month) follow-up, but FAZ area may be become more circular and regular after PRP may be due to reflow of occluded capillary plexus.

To evaluate multifocal electroretinogram (mfERG) parameters in eyes with diabetic macular edema (DME) and its correlation with vision and optical coherence tomography (OCT) features. 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. 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). 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.

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.

To compare the efficacy of an internet-based versus traditional referral system for retinopathy of prematurity (ROP) screening in Iran.Two referral screening systems were compared in this prospective observational study. Group A (internet-based) comprised premature babies who were registered into an online system for screening. Their appointments were scheduled automatically based on standardized criteria. Group B (conventional) comprised premature babies whose referrals were based on oral or written recommendations. Babies were referred based on standard criteria (gestational age, GA,37 weeks or birth weight3000 g).A total of 2115 neonates were screened between October 2011 and October 2012. From these 1896 met the inclusion criteria (group A n = 856, group B n = 1040). Time of first examination for neonates with GA≤27 weeks was 30.07± 2.72 weeks postmenstrual age in group A and 38.52± 7.03 weeks in group B (p = 0.049), and for neonates with GA27 weeks was 4.86 ±1.77 and 8.16 ±4.93 weeks after birth in groups A and B, respectively (p0.001). All registered babies in group A attended their first screening exam. One case (0.1%) of advanced ROP developed in group A (in a patient with poor follow-up compliance), whereas advanced stages of ROP were seen in 26 cases (2.5%) in group B (p0.001).An internet-based registration system for ROP screening resulted in fewer cases of delayed first examination and resulted in fewer babies with advanced ROP.

Objective To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Methods Both eyes of 1932 infants born ≤37 weeks of gestation and/or weighting ≤3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Main outcome measure Patients with ROP requiring treatment. Results The mean GA±SD and birth weight (BW)±SD of the screened patients were 32±2.7 weeks and 1713±516 g, respectively. Using criteria of GA≤32 weeks or BW ≤2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4%ROP requiring treatment in our cohort. Conclusions Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran.

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.

Author(s): Estrago-Franco, M Fernanda; Moustafa, M Tarek; Riazi-Esfahani, Mohammad; Sapkal, Ashish U; Piche-Lopez, Rhina; Patil, A Jayaprakash; Sharma, Ashish; Falatoonzadeh, Payam; Chwa, Marilyn; Luczy-Bachman, Georgia; Kuppermann, Baruch D; Kenney, M Cristina | Abstract: PurposeTo 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.MethodsARPE-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).ResultsThe ARPE-19 cultures treated with B(e)p showed significantly increased ROS/RNS levels (P l 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.ConclusionThe 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.

Aim: To compare refractive error changes in retinopathy of prematurity (ROP) patients treated with diode and red lasers. Methods: A randomized double-masked clinical trial was performed, and infants with threshold or prethreshold type 1 ROP were assigned to red or diode laser groups. Gestational age, birth weight, pretreatment cycloplegic refraction, time of treatment, disease stage, zone and disease severity were recorded. Patients received either red or diode laser treatment and were regularly followed up for retina assessment and refraction. The information at month 12 of corrected age was considered for comparison. Results: One hundred and fifty eyes of 75 infants were enrolled in the study. Seventy-four eyes received diode and 76 red laser therapy. The mean gestational age and birth weight of the infants were 28.6 ± 3.2 weeks and 1,441 ± 491 g, respectively. The mean baseline refractive error was +2.3 ± 1.7 dpt. Posttreatment refraction showed a significant myopic shift (mean 2.6 ± 2.0 dpt) with significant difference between the two groups (p < 0.001). There was a greater myopic shift among children with zone I and diode laser treatment (mean 6.00 dpt) and a lesser shift among children with zone II and red laser treatment (mean 1.12 dpt). The linear regression model, using the generalized estimating equation method, showed that the type of laser used has a significant effect on myopic shift even after adjustment for other variables. Conclusion: Myopic shift in laser-treated ROP patients is related to the type of laser used and the involved zone. Red laser seems to cause less myopic shift than diode laser, and those with zone I involvement have a greater myopic shift than those with ROP in zone II.

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.

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.

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.

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 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.

Bevacizumab, an anti-VEGF antibody, has demonstrated trustworthy effects in treatment of retinal and choroidal neovascularization that both are crucial sight threatening conditions. However, the weak point is the short half-life of the drug in vitreous which necessitates frequent intravitreal injections. Accordingly employing controlled-release drug delivery systems such as polymeric nanoparticles (NPs) has been suggested. In this study albuminated-PLGA-NPs containing bevacizumab were prepared and studied intended for reducing the number of injections. NPs were formulated by double-emulsion method and a single dose of NPs was intravitreally injected to rabbits. The drug concentrations in vitreous and aqueous humor were assayed in different time intervals using ELISA and intraocular pharmacokinetic parameters were calculated. Moreover, coumarin-6 loaded albuminated-PLGA-NPs were employed to evaluate the distribution and persistence of the NPs in the posterior segment. Results revealed that the bevacizumab vitreous concentration maintained above 500 ng mL(-1) for about 8 weeks and 3.3 times elevation was observed in the drug vitreous MRT compared with the control. According to coumarin-6 NP tests, fluorescence emissions in posterior tissues were observed for 56 days which confirmed the nanoparticles persistence in ocular tissues during the test span. Therefore our prepared formulation may offer improvements in treatment of eye posterior segment neovascularization.

Purpose: To report the use of intraoperative spectral domain optical coherence tomography (SD-OCT) for detecting anatomical changes during macular surgery. Methods: In a consecutive case series, 32 eyes of 32 patients undergoing concurrent pars plana vitrectomy and intraoperative SD-OCT for macular hole (MH), epiretinal membrane (ERM) and vitreomacular traction (VMT) were enrolled. Intraoperative changes in retinal thickness and dimensions of the macular hole were measured in patients with ERM and VMT following surgical manipulation using a hand-held SD-OCT device (iVue, Optovue Inc., Fremont, CA, USA). Results: SD-OCT images of sixteen eyes with macular hole were subjected to quantitative and qualitative analysis. All MH dimensions remained stable during consecutive stages of surgery except for MH apex diameter, which showed a significant decrease after internal limiting membrane (ILM) peeling (P=0.025). Quantitative analysis of ten patients with ERM showed a significant decrease in retinal thickness after membrane removal (P=0.018) which did not remain significant until the end of the procedure (P=0.8). In three cases, subretinal fluid was formed after ILM peeling. Quantitative analysis of five patients with VMT showed a decrease in retinal thickness during consecutive steps of the surgery, although these changes were not significant. In two cases, subretinal fluid was formed after ILM peeling. Conclusion: Intraoperative SD-OCT is a useful imaging technique which provides vitreoretinal surgeons with rapid awareness of changes in macular anatomy during surgery and may therefore result in better anatomical and visual outcomes.

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.

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.

Millions of patients are either slowly losing their vision or are already blind due to retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) or because of accidents or injuries. Employment of artificial means to treat extreme vision impairment has come closer to reality during the past few decades. Currently, many research groups work towards effective solutions to restore a rudimentary sense of vision to the blind. Aside from the efforts being put on replacing damaged parts of the retina by engineered living tissues or microfabricated photoreceptor arrays, implantable electronic microsystems, referred to as visual prostheses, are also sought as promising solutions to restore vision. From a functional point of view, visual prostheses receive image information from the outside world and deliver them to the natural visual system, enabling the subject to receive a meaningful perception of the image. This paper provides an overview of technical design aspects and clinical test results of visual prostheses, highlights past and recent progress in realizing chronic high-resolution visual implants as well as some technical challenges confronted when trying to enhance the functional quality of such devices.

Background: Drug abuse could cause complications; infection and overdose are the most prevalent of them. Unreliable history of addicted patients also makes the diagnosis difficult and leads to delayed treatment and poor prognosis. Early recognition and prompt treatment are required to minimize the destructive damage. To our knowledge, there is not any previous report of bilateral eye injection among drug abusers, causing traumatic endophthalmitis in the English literature and our report helps ophthalmologists to think about rare sources of endophthalmitis. Aim: The aim is to emphasize the importance of considering exogenous endophthalmitis in I.V. drug users who abuse drugs. Methods: A 40-year-old I.V. drug user man was referred complaining a history of the pain, redness and impaired vision of both eyes from three days ago. Perilimbal injection and anterior chamber cellular reaction were present in both eyes. Both corneas were hazy; corneal edema, abscess, sealed corneal lacerations and dull red reflex were visible in both eyes. Results: After an ultrasonography based on the suspicion of endophthalmitis, anterior chamber and vitreous aspiration and intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg were performed. The right eye rapidly deteriorated and was eviscerated two days later and the left eye had a good response to medications. Conclusion: This report illustrates that the orbit can be a potential site of drug injection and endophthalmitis should be considered in individuals who abuse drugs.

A 4-year-old boy presented with unilateral endophthalmitis and echography revealed an abscess in the vitreous cavity. A pars plana vitrectomy with intravitreal antibiotic injections was performed with a presumed diagnosis of endophthalmitis; however, the patient returned after 10 days with fibrin reaction in the anterior chamber, iris nodules and cataract. The vitreous sample from the vitrectomy showed Toxoplasma gondii parasite, so he was treated with intravitreal clindamycin and lensectomy. The postoperative fundus examination revealed multifocal white patches with calcified deposits and cytology proved the diagnosis of retinoblastoma. Enucleation was performed in addition to systemic chemotherapy. To our knowledge, this is the first reported case of the coexistence of retinoblastoma and ocular toxoplasmosis.

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. 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. 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

To study predisposing factors of endophthalmitis in patients with open-globe injury.All 2,340 patients with open-globe injury admitted to our center over 5 years were studied retrospectively, and patients with endophthalmitis were compared with other patients.The number of endophthalmitis cases among patients with open-globe injury was 117 eyes, accounting for an incidence of 5.1%. The risk of endophthalmitis was significantly higher among male patients with pure corneal injuries (6.8%), intraocular foreign bodies (9.3%), traumatic lens rupture (7.1%), trauma resulting from needles (22.2%), and shorter lacerations. The existence of hyphema or iris prolapse was associated with lower rates of endophthalmitis. The mean gap between injury time and operation time was longer in the endophthalmitis group (2.1 ± 1.8 vs. 1.1 ± 1.3 days). Patients with endophthalmitis had significantly lower ocular trauma scores compared with other patients.Posttraumatic endophthalmitis is more likely among patients with open-globe injury that are needle related and among those who have intraocular foreign bodies, traumatic lens rupture, smaller wounds, or wounds exclusively in the cornea. Lower ocular trauma scores in this group of patients with penetrating trauma indicated a greater risk of poor visual prognosis. Therefore, it is suggested that necessary measures and immediate treatment be undertaken in high-risk patients.

The goal of this work is to compare the visual and anatomical (central macular thickness; CMT) outcomes of intravitreal bevacizumab (IVB) injections relative to sham treatment in eyes with acute (less than 3 months in duration) branch retinal vein occlusion (BRVO).In a double-masked randomized clinical trial (RCT), patients with acute BRVO were randomly assigned to one of two treatment groups: IVB (two injections of 1.25 mg IVB 6 weeks apart) or sham treatment. Primary outcome measures included changes in best-corrected visual acuity (BCVA) and CMT in optical coherence tomography (OCT) during follow-up (FU) examinations. Any complications secondary to injections were considered secondary outcomes. FU results after 6 and 12 weeks are reported.Eighty-one eyes (43 OD) of 81 patients (47 females) were enrolled in the study. Forty-two patients were enrolled in the IVB group, and 39 patients were enrolled in the sham group. Visual acuity and CMT improved in the IVB group after week 6 (two Snellen lines and 262 μm, respectively) and week 12 (three Snellen lines and 287 μm, respectively). After week 6, visual improvements in the IVB group were significantly increased relative to that of the sham group. However, visual improvements at week 12 were not significantly different between the two groups (1.5 Snellen lines visual improvement in the sham group at week 12).In acute BRVO, two IVB injections resulted in significant improvement of vision and CMT at 6 weeks relative to the sham group. However, the visual improvements in the IVB group were not significantly different from those in the sham group at 12 weeks. IVB injections accelerate an initial improvement of visual acuity but do not have any significant effects on vision after 12 weeks.

PURPOSE To investigate the effects of morphine administered after reperfusion in a rabbit model of ischemic retinopathy. METHODS The right eyes of 54 albino New Zealand rabbits were randomly allocated into nine treatment groups (n = 6 in each group). The eyes in saline-control group received 0.1 mL of phosphate-buffered saline solution intravitreally. In the ischemia-saline group, ischemia was induced by raising the intraocular pressure to 150 mmHg for 60 minutes. Then 0.1 mL of phosphate-buffered saline solution was administered intravitreally 5 minutes after reperfusion. The eyes in three ischemia-morphine groups (ischemia-morphine 0 hour, 1 hour, and 18 hours) received 0.1 mL of morphine (10 micromol/L) intravitreally 5 minutes, 1 hour, or 18 hours after termination of 60 minutes of ischemia, respectively. The eyes in ischemia-naloxone-morphine group received 0.05 mL of naloxone (10 micromol/L) intravitreally followed by injection of 0.05 mL morphine (10 micromol/L) 5 minutes after termination of ischemia. Toxicity controls were performed with morphine (10 micromol/L) and naloxone (10 micromol/L) without ischemia. Histologic evaluation was performed for all groups on the seventh postoperative day. RESULTS Sixty minutes of ischemia led to severe cell loss in ganglion cell layer and thinning of the inner nuclear layer in ischemia-saline group compared with that of the saline-control group (P < 0.001). Thickness of the inner plexiform layer to the inner limiting membrane (a measure of inner retinal thickness) was significantly increased due to edema (P < 0.001). Administration of morphine 5 minutes after reperfusion significantly improved all of the above mentioned indices compared with ischemia-saline group (P < 0.001). Administration of morphine 1 hour after reperfusion had also a significant effect on the improvement of above mentioned indices compared with saline-control group (P < 0.05). However, the number of ganglion cells was significantly higher in ischemia-morphine 0 hour group compared with ischemia-morphine 1 hour group (P < 0.001). Morphine treatment 18 hours after reperfusion did not change the amount of injury. Administration of naloxone 5 minutes before morphine abolished most of the morphine protective effects. CONCLUSION Intravitreal administration of morphine immediately after reperfusion maximally protects retina against ischemia-reperfusion injury. Pharmacologic evidence suggests that this protective phenomenon may be mediated in part by opioid receptors.

PURPOSE: To report the incidence, severity and risk factors of retinopathy of prematurity (ROP) in premature infants with late ROP examination in Farabi Eye Hospital. METHODS: In a retrospective study from January 2001 to July 2007, hospital records of premature infants who were examined later than 9 weeks after birth were reviewed to determine the incidence, severity and possible risk factors of ROP including gender, singleton or multiple gestations, gestational age (GA), birth weight (BW), oxygen therapy, blood transfusion, phototherapy, respiratory distress syndrome (RDS), mechanical ventilation, intraventricular hemorrhage and sepsis as well as age at initial examination. RESULTS: Out of a total of 797 infants referred for ROP screening during the study period, 216 (27.1%) had late examinations at a mean age of 141.7±150.4 (range 64-1,460) days. Of these, 87 (40.3%) had different stages of ROP, 65 (30.1%) had stage 4 or 5 disease including 34 (16.2%) infants with stage 5 ROP in both eyes which was untreatable. Lower GA (P < 0.001), RDS (P=0.041) and blood transfusion (P=0.009) were associated with the development of ROP. CONCLUSION: The overall prevalence of ROP and the incidence of severe ROP in particular, were unacceptably high in premature infants with late screening. These findings necessitate interventions to optimize timely referral for screening of premature infants.

To evaluate the effect of topically administered doxycycline in various doses; the combination of triamcinolone acetonide and low-molecular-weight heparin (LMWH); and the combination of triamcinolone acetonide and doxycycline on experimental corneal neovascularization in rats.This project is the combination of 2 separate studies. First, the chemical cauterization of corneas in 36 eyes of 36 Long Evans male rats was performed by using silver nitrate/potassium nitrate sticks. Topical instillation of doxycycline at 0.05% (pH = 3.3), 0.1% (pH = 3.1), 1% (pH = 2.3), 2% (pH = 2.1), 2% (pH neutralized to 7.4), and normal saline continued for 7 days. Second, the chemical cauterization of the corneas in 24 eyes of 24 rats was achieved by application of silver nitrate/potassium nitrate sticks. Topical instillation of triamcinolone acetonide (10 microg/mL) and either LMWH (10 mg/mL) or doxycycline (10 mg/mL) was compared with normal saline treatment of 7 days. For both studies, the percent area of the cornea covered by neovascularization and scar in each group was calculated separately by using computer software on digital photographs. All corneas were evaluated histopathologically in study and control groups.The mean percent area of corneal neovascularization determined in the eyes given doxycycline 0.05%, 0.1%, 1%, 2%, and 2% (pH neutralized) study groups and control groups was 69.8% +/- 18.0%, 64.5% +/- 14.0%, 56.4% +/- 20.8%, 54.8% +/- 6.0%, 36.2% +/- 4.3%, and 69.4% +/- 5.7%, respectively. The mean of percent area of neovascularization in the 2% doxycycline (pH neutralized) doxycycline group was significantly less than that of the control group and the1% doxycycline concentrations (P0.05). The percent corneal neovascularization in the 2% (pH neutralized) doxycycline group was not significantly different from that of the 1% and 2% doxycycline groups (P0.05). There was no significant difference in percent area of corneal scar between control and study groups (P0.05). The mean percent area of corneal neovascularization in triamcinolone acetonide and LMWH, triamcinolone acetonide and doxycycline, and control groups was 2.35% +/- 4.42%, 9.42% +/- 6.8%, and 64.7% +/- 10.0%, respectively. The mean percent area of neovascularization in the triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline groups was significantly different from that of the control group (P = 0.001 for both). There was no significant difference between study groups with regard to percent area of neovascularization or percent area of corneal scar between the control and study groups.Topically administered combinations of triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline had effects that contributed to efficient suppression of corneal neovascularization; these drugs were ineffective at similar concentrations used alone. Topically administered 2% (pH neutralized) doxycycline has antiangiogenic effects, which contributed to significant suppression on corneal neovascularization. This drug may be therapeutically beneficial in treatment of corneal neovascularization in clinical trials.

In this report, we present four patients with type 1 diabetes of long duration (more than 20 years) who had multiple joint contractures (Rosenbloom syndrome) and who presented with reduced vision and advanced proliferative diabetic retinopathy. All of the cases had short stature which was non-familial and all had other microvascular complications (nephropathy and neuropathy). It seems that limited joint mobility (LJM) is a risk factor not only for microvascular complications, but also for more severe and advanced proliferative retinopathy.

Purpose To report the visual acuity, enucleation rates, and initial mortality after transvitreal endoresection of posterior uveal melanoma. Methods Twenty consecutive patients with medium-sized posterior choroidal melanomas were treated. Vitrectomy was performed, followed by posterior hyaloid dissection, retinotomy, melanoma removal with a vitrectomy probe, retinal reattachment with perfluorocarbon liquid, and silicone oil or gas exchange. Results Twenty patients (13 men [65%] and 7 women [35%]) were included in the study. The mean patient age +/- SD was 47.1 +/- 16 years (range, 22-70 years). Tumor thickness and tumor diameter ranged from 5.5 mm to 11 mm and 8.0 mm to 15.7 mm, respectively. Preoperative visual acuity ranged from hand motion to 20/40, and postoperative visual acuity ranged from no light perception to 20/30. Two eyes (10%) were enucleated during tumor resection due to severe bleeding. Enucleation was performed on 3 eyes (15%) during follow-up due to tumor recurrence at the edge of surgical coloboma in 1 patient, new focus of tumor in another sector distant from surgical coloboma in 1 patient, and painful blind eye in 1 patient. Fifteen eyes (75%) were saved. One patient (5%) died of metastasis to the liver. The mean follow-up period +/- SD was 89.55 +/- 38.4 months (range, 24-132 months. Conclusion These data suggest that transvitreal endoresection of posterior uveal melanoma is an acceptable management option to conserve the globe and functional vision in selected patients. Distant metastasis is an infrequent event in this modality of treatment.

Non-syndromic autosomal recessive Retinitis Pigmentosa (arRP) is a highly heterogeneous genetic visual disorder with a large number of causative genes. We aimed to determine the power of Whole Exome Sequencing (WES) in the identification of the genes responsible for non-syndromic arRP among Iranian patients.We used WES, followed by the Sanger sequencing to identify the underlying gene mutations causing non-syndromic arRP.Our study revealed disease-causing mutations in known arRP genes for 10 of the 13 families studied (76.9%). These mutations included two-frameshift insertion/deletion in CRB1 and ABCA4, one splicing mutation in PDE6B, four missense mutations in RP1, CRB1, PANK2 and IFT140, as well as three stop codon mutations in RDH12, PRCD, and C2orf71. Three remaining families harbored no mutation in previously known RP genes. Of the 10 diseases causing mutations identified among the investigated Iranian patients with non-syndromic arRP, eight variants had not been reported previously. We confirmed segregation of all 10 mutations with disease phenotypes in our studied population.This study supports the genetic heterogeneity of non-syndromic arRP in Iranian patients, and provides an opportunity to show the effectiveness of WES in the identification of pathogenic mutations among patients with non-syndromic arRP born to consanguineous parents.

Purpose To design software with a novel algorithm, which analyzes the tortuosity and vascular dilatation in fundal images of retinopathy of prematurity (ROP) patients with an acceptable accuracy for detecting plus disease. Methods Eighty-seven well-focused fundal images taken with RetCam were classified to three groups of plus, non-plus, and pre-plus by agreement between three ROP experts. Automated algorithms in this study were designed based on two methods: the curvature measure and distance transform for assessment of tortuosity and vascular dilatation, respectively as two major parameters of plus disease detection. Results Thirty-eight plus, 12 pre-plus, and 37 non-plus images, which were classified by three experts, were tested by an automated algorithm and software evaluated the correct grouping of images in comparison to expert voting with three different classifiers, k-nearest neighbor, support vector machine and multilayer perceptron network. The plus, pre-plus, and non-plus images were analyzed with 72.3%, 83.7%, and 84.4% accuracy, respectively. Conclusions The new automated algorithm used in this pilot scheme for diagnosis and screening of patients with plus ROP has acceptable accuracy. With more improvements, it may become particularly useful, especially in centers without a skilled person in the ROP field.