Retinal imaging and Alzheimer's disease: a future powered by Artificial Intelligence.

Alzheimer's disease (AD) is a neurodegenerative condition that primarily affects brain tissue. Because the retina and brain share the same embryonic origin, visual deficits have been reported in AD patients. Artificial Intelligence (AI) has recently received a lot of attention due to its immense power to process and detect image hallmarks and make clinical decisions (like diagnosis) based on images. Since retinal changes have been reported in AD patients, AI is being proposed to process images to predict, diagnose, and prognosis AD. As a result, the purpose of this review was to discuss the use of AI trained on retinal images of AD patients. According to previous research, AD patients experience retinal thickness and retinal vessel density changes, which can occasionally occur before the onset of the disease's clinical symptoms. AI and machine vision can detect and use these changes in the domains of disease prediction, diagnosis, and prognosis. As a result, not only have unique algorithms been developed for this condition, but also databases such as the Retinal OCTA Segmentation dataset (ROSE) have been constructed for this purpose. The achievement of high accuracy, sensitivity, and specificity in the classification of retinal images between AD and healthy groups is one of the major breakthroughs in using AI based on retinal images for AD. It is fascinating that researchers could pinpoint individuals with a positive family history of AD based on the properties of their eyes. In conclusion, the growing application of AI in medicine promises its future position in processing different aspects of patients with AD, but we need cohort studies to determine whether it can help to follow up with healthy persons at risk of AD for a quicker diagnosis or assess the prognosis of patients with AD.

Role of complement factor B rs4151667 (L9H) polymorphisms and its interactional role with CFH Y402H and C3 rs2230199 (R102G) risk variants in age-related macular degeneration: a case control study.

BACKGROUND: Age-related Macular Degeneration (AMD) is a complex eye disease, which is genetically associated with different susceptibility loci. We planned to investigate the possible association of Complement Factor B (CFB) rs4151667 (L9H) variants and their possible interaction with Complement Factor H (CFH) Y402H and Complement factor 3 (C3) rs2230199 (R102G) in AMD. METHODS: This case-control association study included 216 advanced type AMD patients and 191 healthy individuals for evaluation. Extracted-DNA samples were genotyped for the polymorphic regions of CFB rs4151667 (L9H), CFH Y402H and C3 rs2230199 (R102G). RESULTS: The distribution of CFB rs4151667 (L9H) genotypes was not significantly different in the AMD patients compared to that of controls (P = 0.18). The AT genotype frequencies for CFB was non significantly lower in AMD group (6.5% vs. 13.1%, AOR = 0.49, CI = 0.23-1.04, P = 0.064(. The A allele of CFB rs4151667 (L9H) was found to be non-significantly lower in AMD patients. CFB rs4151667 (L9H) had no protective interactional effect against CFH (Y402H) and C3 (R102G) risk variants. CONCLUSIONS: This study showed that the protective role of CFB rs4151667 (L9H) in AMD is not significant and it has no significant protective interactional effect against CFH (Y402H) and C3 (R102G) risk variants.

Association of polymorphisms of complement factor I rs141853578 (G119R) with age-related macular degeneration in Iranian population.

BACKGROUND: Age-related macular degeneration (AMD) is a complex disease, and recent studies have shown role of complement system genes in its development. Complement factor I regulates the complement pathways, and relationship between CFI polymorphisms and AMD is controversial. We evaluated the possible association of complement factor I rs141853578 (G119R) variation with advanced AMD in Iranian patients. MATERIALS AND METHODS: We included 371 case-control samples consisting of 220 advanced AMD patients and 151 genetically unrelated healthy controls. Extracted DNA samples amplified to obtain fragment including the polymorphic complement factor I rs141853578 (G119R) region. RESULTS: The distribution of the genotypes was significantly different in the AMD patients compared to that of controls (p = 0.035). The TT genotype frequencies for CFI were significantly higher in AMD group (7.7 vs. 2%, OR 4.67, CI 1.33-16.45, p = 0.016). This significant difference was maintained after adjustment for the effects of age and gender (OR 5.09, CI 1.42-18.20, p = 0.012). The minor allele frequency (T allele) was also significantly higher in AMD patients compared to that of controls (29.3 vs. 21.5% OR 1.51, CI 1.07-2.13, p = 0.018). CONCLUSION: Current study showed that CFI rs141853578 (G119R) is a risk factor for developing advanced type AMD. This study also suggests that the frequency of G119R polymorphism in our population is not as rare as reported from other populations.

Serum adropin level in wet-type age-related macular degeneration.

PURPOSE: Our objective was to compare the serum Adropin levels between patients with wet-type Age-Related Macular Degeneration (AMD) and otherwise healthy individuals. METHOD: The study included 45 patients with wet-type AMD and 45 individuals without age-related macular degeneration. Patients with co-morbidities such as diabetes, hypertension, autoimmune diseases, and a previous history of visual impairment; were excluded. FBS, Hemoglobin A1C (HbA1C), lipid profile, and serum Adropin level were checked. RESULTS: The mean serum Adropin level of patients with wet-type AMD was significantly lower than the control group (P-value < 0.001). Also, the mean High-sensitivity C-reactive protein ( hsCRP) level and High Density Lipoprotein (HDL) were significantly higher in wet-type AMD patients (P-value = 0.031 and < 0.001 respectively). CONCLUSIONS: In our study, wet-type AMD was associated with a lower level of serum Adropin. Because of Adropin involvement in glucose metabolism and age-related changes, it may have a role in the pathogenesis of AMD, but it requires more investigations at the molecular level to elucidate its function.

Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy.

PURPOSE: To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). METHODS: In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120-200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. RESULTS: The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69±0.32 pg/ml in the CaD group and 0.86±0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). CONCLUSIONS: Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients.

Serum paraoxonase phenotype distribution in exudative age-related macular degeneration and its relationship to homocysteine and oxidized low-density lipoprotein.

PURPOSE: Disequilibrium between oxidative stress and antioxidant levels has been proposed as an important case of exudative age-related macular degeneration (AMD). The aim of the present study was to investigate homocysteine (Hcy) level and antioxidant paraoxonase 1 (PON1) activity within its phenotypes together with oxidized low-density lipoprotein (OX-LDL) levels in the patients with exudative AMD. METHODS: Serum PON1 activity and plasma Hcy and OX-LDL levels were analyzed in 45 exudative AMD patients and compared with 45 healthy controls. Paraoxonase 1 activity was measured in serum using paraoxon and phenylacetate as substrates. The PON1 phenotype was determined using double-substrate method. Homocysteine and OX-LDL levels were determined by enzyme-linked immunosorbent assay method. RESULTS: The distribution of PON1 phenotypes was significantly different between the patients with exudative AMD and control subjects (chi-square = 6.17, P = 0.01). AA phenotype with low activity was significantly more frequent in exudative AMD patients compared with healthy subjects (62.2% vs. 35.6%, respectively). Other phenotype frequencies in the patients compared with controls were as AB phenotype (intermediate activity) 28.9% versus 46.7% and BB phenotype (high activity) 8.9% versus 17.8%, respectively. Except in BB phenotype (P = 0.2), patients with AA and AB phenotypes had higher plasma Hcy levels in comparison to those of controls (P = 0.02 and P = 0.03, respectively). The mean OX-LDL levels, in all 3 phenotypes (P < 0.05), and OX-LDL/high-density lipoprotein ratio, in AA and AB phenotypes (P = 0.001, P = 0.1, respectively) but not in BB (P = 0.1), were significantly higher in the patients than controls. No significant differences in comparison of Hcy and OX-LDL levels between 3 PON1 phenotypes in both control (P = 0.6 for Hcy, P = 0.7 for OX-LDL) and patients (P = 0.8 for Hcy, P = 0.6 for OX-LDL) were found CONCLUSION: Increased plasma OX-LDL levels and ratios of OX-LDL/high-density lipoprotein, as biomarkers of lipoprotein oxidative stress, higher levels of Hcy, as oxidant agent, and more common low or intermediate PON1 activity in patients with exudative AMD, compared with controls, indicate that PON1 activity is insufficient to explain the increased oxidative stress observed in exudative AMD.

Oxidative DNA damage and total antioxidant status in glaucoma patients.

PURPOSE: To evaluate DNA damage markers and the antioxidant status of serum and aqueous humor in glaucoma patients. METHODS: Aqueous humor and serum samples were obtained at the time of surgery from 28 patients with glaucoma and 27 patients with cataracts. Total antioxidant status (TAS) and 8-hydroxy-2´-deoxyguanosine (8-OHdG) levels of all samples were determined by spectrophotometric and enzyme-linked immunosorbent assay methods. RESULTS: Aqueous levels of 8-OHdG were higher in glaucoma patients than in the cataract group (4.61±2.97 ng/ml versus 1.98±0.70 ng/ml, p=0.002). Serum levels of 8-OHdG were also higher in glaucoma patients than in the cataract group (17.80±8.06 ng/ml versus 13.63±3.54 ng/ml, p=0.046). The TAS levels of serum (0.55±0.13 mmol/lit versus 0.70±0.14, p=0.001), and aqueous humor (0.23±0.13 mmol/lit versus 0.34±0.15, p=0.001) in glaucoma patients were lower than in cataract patients. CONCLUSIONS: Our findings provide evidence that oxidative DNA damage increases and TAS decreases in the serum and aqueous humor of glaucoma patients. These findings support the hypothesis that the formation of reactive oxygen species and/or a decrease in TAS may have an important role in the pathogenesis of glaucoma.

The effect of Helicobacter pylori treatment on remission of idiopathic central serous chorioretinopathy.

PURPOSE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) treatment on remission of idiopathic central serous chorioretinopathy. METHODS: Twenty-five patients with idiopathic central serous chorioretinopathy (ICSCR) who were infected with H. pylori were treated with an anti-H. pylori treatment; another twenty-five patients with the same clinical presentations served as the control. Baseline examination and follow up visits at 2, 4, 6, 8, 12, and 16 weeks after the onset of treatment included visual acuity testing and subretinal fluid measurement. The difference between mean visual acuity at the end of 16 weeks and the time of subretinal fluid reabsorption was compared between the two groups. RESULTS: Subretinal fluid reabsorption time was 9.28±3.20 weeks in the treatment group and 11.63±3.18 weeks in the control group, which was statistically significant (p=0.015). After 16 weeks, mean visual acuity improved to 0.003±0.01 (logMAR) in the treatment group and 0.004±0.02 (logMAR) in the control group. This improvement did not represent a statistically significant difference (p=0.97). CONCLUSIONS: An anti-H. pylori treatment regimen is effective in the treatment of idiopathic central serous chorioretinopathy patients and anti-H. pylori treatment can provoke the faster reabsorption of subretinal fluid.

Plasma oxidized LDL and thiol-containing molecules in patients with exudative age-related macular degeneration.

PURPOSE: It was proposed that total thiols (tSH) as powerful reducing agents and oxidized low-density lipoprotein (OX-LDL) may be associated with development of choroidal neovascularization in exudative age-related macular degeneration (E-ARMD). METHODS: In a case-control study, 45 patients with E-ARMD were compared with 45 sex- and age-matched healthy controls. The levels of plasma homocysteine (Hcy) and OX-LDL as oxidant agents, and of tSH and glutathione (GSH) as antioxidant markers, were estimated in E-ARMD patients and controls. RESULTS: The levels of Hcy (15.4±7.2 µM versus 10.7±3.7 µM; p=0.001) and OX-LDL (52.2±13.8 U/l versus 37.8±10.8 U/l; p=0.001) were statistically higher, while GSH (1.10±0.97 µM versus 2.09±1.04 µM; p=0.001) and tSH (0.31±0.06 mM versus 0.35±0.05 mM; p=0.001) were statistically lower, in the patients with E-ARMD than in the control group, respectively. The plasma OX-LDL concentration also exhibited a positive and significant correlation with Hcy (r=0.719, p=0.001) in patients with E-ARMD. CONCLUSIONS: Lower GSH and tSH as antioxidant and higher Hcy levels as oxidant agents in E-ARMD patients may have resulted in an oxidative environment that was associated with OX-LDL. Further studies with more cases are required to confirm the hypothesis.

Aqueous humor hepcidin prohormone levels in patients with primary open angle glaucoma.

PURPOSE: This study was designed to evaluate the levels of Interleukin-6 (IL6) and Hepcidin prohormone (Hep) in the serum and aqueous humor of patients with primary open-angle glaucoma (POAG), as well as those with senile cataract as a control group. METHODS: Levels of IL6 and Hep were measured by enzyme-linked immunosorbent assay (ELISA) methods in serum and aqueous humor aspirates taken from 45 patients (POAG=20, Control=25) during anterior segment surgery. RESULTS: The mean aqueous humor Hep concentration in eyes with POAG was significantly higher than that controls (34.55±23.01 ng/ml versus 20.82± 24.63 ng/ml, p=0.04). There was no significant difference between the serum Hep concentration of POAG and the control group (359.46±113.03 ng/ml versus 287.36±130.53 ng/ml, p=0.08). There was also no significant difference between either serum (6.18±5.22 versus 10.84±3.37, pg/ml p=0.112) or aqueous humor (4.39±3.06 versus 5.79±2.63, pg/ml p=0.14) IL6 concentrations of POAG and the control groups. No significant correlations were found between aqueous humor and serum Hep and IL6 levels in either POAG or the control groups (p>0.05). CONCLUSIONS: The aqueous humor Hep level may exist locally and independent from the IL6 increase in patients with POAG, suggesting that Hep might represent a bridge protein between local inflammation and the consequent loss of retinal ganglion cells.

Preventive effect of onion juice on selenite-induced experimental cataract.

PURPOSE: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. MATERIALS AND METHODS: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). RESULTS: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). CONCLUSION: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

Lipoprotein(a), homocysteine, and retinal arteriosclerosis.

PURPOSE: Elevated levels of lipoprotein(a) [Lp(a)] and homocysteine (Hcy) have been implicated as risk factors for vascular diseases. The study was performed to explore the possible relationship between retinal arteriosclerosis and serum Lp(a) and Hcy levels. METHODS: Study subjects consisted of 80 nonsmoking male patients with retinal arteriosclerosis and 54 healthy nonsmoker males as controls. Retinal arteriosclerosis was graded according to the Scheie classification. Serum levels of lipids, lipoproteins, Lp(a), and Hcy were measured by standard methods. RESULTS: The serum level of Hcy was higher in patients (24.2+/-8.1 micromol/l) than controls (10.5+/-4.1 micromol/l); p<0.01. Serum levels of Lp(a) in patients (47.9+/-33.1 mg/dl) was also higher than controls (11.7+/-7.6 mg/dl); p<0.01. There was a significant direct linear correlation between the degree of retinal arteriosclerosis and Lp(a) level (r=0.61, p<0.01), the degree of retinal arteriosclerosis and Hcy level (r=0.72, p<0.01), and also between Lp(a) and Hcy levels (r=0.67, p<0.01). CONCLUSIONS: The association between retinal arteriosclerosis and serum Lp(a) and Hcy levels suggests that Lp(a) as well as Hcy could play a role in the development of retinal arteriosclerosis.

Association of polymorphisms in complement component 3 with age-related macular degeneration in an Iranian population.

BACKGROUND: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Inflammatory mediators play an important role in AMD pathogenesis and immune-related gene polymorphisms are shown to increase the risk. Complement system is an important mediator of the immunity system and several genes encoding proteins involved in this system are associated with susceptibility to AMD. The central element of the complement cascade, C3 has been a plausible candidate since its cleavage product C3a was found in drusen. This study was planned to evaluate the association of C3-rs2230199 (R102G) variants with advanced type AMD in this cohort. MATERIALS AND METHODS: In this case-control study, 494 participants consisting of 266 AMD patients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated healthy controls were enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region. RESULTS: The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p = 0.001).The Odds Ratio compared to CC individuals was 1.69 (95% CI 1.15-2.49) for GC individuals and 6.48 (95% CI1.87-22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95% CI 0.48-11) for the G allele. GG and GC genotypes and G allele were significantly associated with both types of advanced-AMD. Individuals carrying GG genotype have over a six-fold risk of developing AMD in comparison to those carrying the CC genotype in this cohort. Our meta-analysis pooled data showed that our homozygous individuals for GG have a higher risk of AMD compared to previous publications in different nations (p = 0.017). CONCLUSIONS: Our study shows C3 to be a relatively strong susceptibility gene for advanced-type-AMD (exudative-and-geographic-atrophy) in an Iranian population.

Joint association of complement component 3 and CC-cytokine ligand2 (CCL2) or complement component 3 and CFH polymorphisms in age-related macular degeneration.

BACKGROUND: To determine the joint effect of complement component 3(C3 R102G) with CC-cytokine ligand2 (CCL2-2518) or complement factor H (CFH) Y402H polymorphisms on advanced age-related macular degeneration (AMD). METHODS: In this case-control study, 233 patients with advanced AMD and 159 unrelated healthy controls enrolled for evaluation. Selected polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: A combination of AA CCL2 (rs1024611) and GG C3 (R102G) genotypes resulted in a super-additivity of the risks: OR = 10.13, 95% CI 1.04-98.49, p = 0.04, adjusted OR = 7.74, 95% CI 0.71-84.75, p < 0.1, adjusted synergy indices: relative excess risk due to interaction (RERI) = 1.38, the attributable proportion due to interaction (AP) = 24.7% and the synergy index (S) = 1.43. Combination of at-risk genotypes of CFH Y402H and C3 R102G resulted in a strong super-additive risk: adjusted OR = 22.65, 95% CI 2.32-220.91, p = 0.007, adjusted AP = 90.4% and the S = 12.86. Attributable proportion of risk owing to C3-CCL2 and C3-CFH interaction calculated at 25% and 90% for advanced AMD. CONCLUSION: We have previously shown a strong association of C3 (R102G) and CFH Y402H with AMD whereas no association was found for CCL2-2518. This study enclosed strong synergistic association of risk genotypes of C3 and CFH Y402H with AMD. We also revealed synergistic influence of CCL2-2518 and the at-risk genotype of the C3 in AMD with an estimated AP = 50.9% (adjusted AP = 24.7%). Present findings show that CCL2-2518 polymorphism is not an innocent bystander in AMD susceptibility when combined with the at-risk genotype of C3 (R102G).

Association of the DNA repair SMUG1 rs3087404 polymorphism and its interaction with high sensitivity C-reactive protein for age-related macular degeneration in Iranian patients.

BACKGROUND: Age-related macular degeneration (AMD) is a complex disease and recently the role of DNA repairing genes in its susceptibility has been studied. It has been hypothesized that polymorphism in DNA repair system genes reduce the capacity to repair DNA damages which may lead to a greater susceptibility to AMD. C-reactive protein (CRP) production is shown to enhance inflammatory processes by increasing oxidative stress and inducing DNA damage. We planned to evaluate the possible association of SMUG1 variants and their possible interaction with high sensitivity CRP levels in AMD. MATERIALS AND METHODS: We included 500 case-control samples consisting of 279 advanced type AMD patients and 221 genetically unrelated healthy controls enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region SMUG1 rs3087404. We calculated relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) to clarify possible interaction of different genotypes and CRP levels for AMD. RESULTS: The distribution of the genotypes were not significantly different in the AMD patients compared to that of controls (p = 0.849). The allele frequency for SMUG1 was not different between study groups. No difference of SMUG1 polymorphism between case and control groups was evident in higher CRP levels (CRP>3mg/dl) compared with lower CRP levels. SMUG1/CRP synergy indices calculated as RERI = -0.12 and AP = -0.18 while S was not calculable. CONCLUSIONS: Our study showed that c.-31A/G-SMUG1 genotypes/alleles do not have any association with the occurrence or severity of advanced type AMD. There was no interaction of CRP levels and SMUG1 genotypes in AMD susceptibility.

The effect of posterior subtenon methylprednisolone acetate in the refractory diabetic macular edema: a prospective nonrandomized interventional case series.

BACKGROUND: To investigate the efficacy of posterior subtenon methylprednisolone acetate injection in treatment of refractory diffuse clinically significant diabetic macular edema (CSME). METHODS: In a prospective, nonrandomized, interventional case series, 52 eyes were diagnosed with CSME and treated with at least two sessions of laser photocoagulation according to Early Treatment Diabetic Retinopathy Study guidelines. At least 3 months after laser therapy, eyes with a residual central macular thickness were offered posterior subtenon injection of 40 mg methylprednisolone acetate. Main outcome measures were visual acuity, macular thickness and intraocular pressure. Potential complications were monitored, including intraocular pressure response, cataract progression and scleral perforation. RESULTS: Mean baseline visual acuity (in logMAR) improved significantly (p = 0.003) from 0.8 +/- 0.36 to 0.6 +/- 0.41 at 3 months. Mean foveal thickness decreased from 388 +/- 78 mum at baseline to 231 +/- 40 mum after 3 months (p < 0.0001). Visual acuity improvement in eyes with CSME with extrafoveal hard exudates was significant (p = 0.0001), but not significant in eyes with CSME with subfoveal hard exudates (p = 0.32). Intraocular pressure increased from 14.7 +/- 2.0 mmHg (range, 12-18 mmHg) to a maximum value of 15.9 +/- 2.1 mmHg (range, 12-20 mmHg) during the follow-up period. Complications in two eyes developed focal conjunctival necrosis at the site of injection. CONCLUSION: Posterior subtenon methylprednisolone acetate may improve early visual outcome in diffuse diabetic macular edema that fails to respond to conventional laser photocoagulation. Visual acuity improvement in eyes with CSME with extrafoveal hard exudates was significant; and this improvement is depends on location of hard exudates. Further study is needed to assess the long-term efficacy, safety, and retreatment.

Evaluation of CC-cytokine ligand 2 and complementary factor H Y402H polymorphisms and their interactional association with age-related macular degeneration.

PURPOSE: To evaluate the association of CC-cytokine ligand 2 CCL2-2518 (rs1024611) single nucleotide polymorphism, complement factor H (CFH Y402H) and their possible interaction in developing advanced age-related macular degeneration (AMD). METHODS: In this case-control study, DNA samples from 266 patients with advanced AMD and 229 healthy controls were genotyped for CCL2 polymorphism and also 254 patients and 164 healthy controls were genotyped for CFH polymorphism. The possible associations of these polymorphisms with susceptibility to AMD independently and in different joint combinations were evaluated. RESULTS: The genotype frequency for CFH was found to be significantly different between AMD and normal controls (31.5% versus 20.7%, OR = 3.56, p < 0.001 for CC and 52.4% versus 41.5%, OR = 2.96, p < 0.001 for CT genotype). However, no significant association between CCL2 polymorphism and AMD was observed in this cohort (OR = 1.15 and OR = 0.8, p = 0.172). Interestingly, studying the joint effects of two genotypes (TT genotype of CFH Y402H and AG genotype of CCL2-2518) showed more significant protective effect against AMD (p = 0.0001), while the risk effect of CC and CT genotypes of CFH was only visible in the presence of AA genotype of CCL2-2518 (p = 0.044 and p = 0.05). CONCLUSION: Complement factor H Y402H polymorphism is strongly associated with advanced type AMD. Although this study revealed no association of CCL2-2518 with AMD, the risk effect of CFH genotypes was only visible in the presence of AA genotype of CCL2-2518. AG genotype of CCL2-2518 in combination with TT genotype of CFH Y402H showed significant protective effect against AMD.

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.

Detection of retinal capillary nonperfusion in fundus fluorescein angiogram of diabetic retinopathy.

INTRODUCTION: Retinal capillary nonperfusion (CNP) is one of the retinal vascular diseases in diabetic retinopathy (DR) patients. As there is no comprehensive detection technique to recognize CNP areas, we proposed a different method for computing detection of ischemic retina, non-perfused (NP) regions, in fundus fluorescein angiogram (FFA) images. METHODS: Whilst major vessels appear as ridges, non-perfused areas are usually observed as ponds that are surrounded by healthy capillaries in FFA images. A new technique using homomorphic filtering to correct light illumination and detect the ponds surrounded in healthy capillaries on FFA images was designed and applied on DR fundus images. These images were acquired from the diabetic patients who had referred to the Nikookari hospital and were diagnosed for diabetic retinopathy during one year. Our strategy was screening the whole image with a fixed window size, which is small enough to enclose areas with identified topographic characteristics. To discard false nominees, we also performed a thresholding operation on the screen and marked images. To validate its performance we applied our detection algorithm on 41 FFA diabetic retinopathy fundus images in which the CNP areas were manually delineated by three clinical experts. RESULTS: Lesions were found as smooth regions with very high uniformity, low entropy, and small intensity variations in FFA images. The results of automated detection method were compared with manually marked CNP areas so achieved sensitivity of 81%, specificity of 78%, and accuracy of 91%.The result was present as a Receiver operating character (ROC) curve, which has an area under the curve (AUC) of 0.796 with 95% confidence intervals. CONCLUSION: This technique introduced a new automated detection algorithm to recognize non-perfusion lesions on FFA. This has potential to assist detecting and managing of ischemic retina and may be incorporated into automated grading diabetic retinopathy structures.