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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PURPOSE: To compare the efficacy and safety of 1.25 mg versus 2.5 mg intravitreal bevacizumab (IVB) for treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). METHODS: In this randomized clinical trial, consecutive patients with active CNV associated with AMD received 1.25 mg or 2.5 mg IVB. Best corrected visual acuity (BCVA), foveal thickness and side effects of therapy were evaluated one and three months after intervention. RESULTS: Overall 86 subjects were enrolled and completed the scheduled follow-up. Forty seven and 39 patients received 1.25 and 2.5 mg IVB respectively. The study groups were balanced in terms of baseline characteristics such as age, BCVA and foveal thickness. Mean improvement in BCVA was 0.06±0.3 logMAR in the 1.25 mg group and 0.07±0.34 logMAR in the 2.5 mg group (P=0.9). Mean decrease in foveal thickness was 49±36 µm in the 1.25 mg group and 65±31µm in the 2.5 mg group (P=0.6). Three cases of vitreous reaction and one case of massive subretinal hemorrhage were observed in the 2.5 mg group. CONCLUSION: Double dose (2.5 mg) IVB does not seem to be more effective than regular dose (1.25 mg) injections for treatment of CNV due to AMD and may lead to more complications.

PURPOSE: To investigate the correlation between retinal nerve fiber layer (RNFL) thickness determined by optical coherence tomography (OCT) and visual field (VF) parameters in patients with optic atrophy. METHODS: This study was performed on 35 eyes of 28 patients with optic atrophy. RNFL thickness was measured by OCT (Carl Zeiss, Jena, Germany) and automated perimetry was performed using the Humphrey Field Analyzer (Carl Zeiss, Jena, Germany). The correlation between RNFL thickness and VF parameters was evaluated. RESULTS: Mean global RNFL thickness was 44.9±27.5 µm which was significantly correlated with mean deviation score on automated perimetry (r=0.493, P=0.003); however, no significant correlation was observed between visual field pattern standard deviation and the corresponding quadrantic RNFL thickness. In a similar manner, no significant association was found between visual acuity and RNLF thickness. CONCLUSION: Mean global RNFL thickness as determined by OCT seems to be correlated with VF defect depth as represented by the mean deviation score on Humphrey VF testing. OCT may be used as an objective diagnostic tool in the evaluation of patients with optic atrophy.