Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics.

Purpose: Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment. Methods: The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits' eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC). Results: The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug. Conclusion: PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization.

A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy.

Purpose: Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the underlying cause. Patients show a high level of ornithine in body fluids which may be controlled by low protein diets. Pyridoxine (vitamin B6) supplementation may also be effective, however, most patients appear to be nonresponsive to this modality of treatment. Case Report: Here, we report a characterized case of a vitamin B6-responsive GACR who had a splicing mutation in the OAT gene. The GACR diagnosis was confirmed through the clinical features, imaging, biochemical findings, and whole-exome sequencing (WES) results. WES data revealed the splicing mutation in intron 4 of the OAT gene (NM_001322967: c.425-1G>A). Conclusion: Our knowledge about the diagnosis and treatment of GACR can be improved by identifying novel mutations in the OAT gene and accurate follow-up of the patients to determine how they respond to treatment.

Vision-related quality of life in patients with retinal vein occlusion.

PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.

A health terminological system for inherited retinal diseases: Content coverage evaluation and a proposed classification.

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

Are inner nuclear layer ischemic lesions hidden indicators of retinal vein occlusion risk? A case-control study.

PURPOSE: To investigate the association between retinal vein occlusion (RVO) and evidence of previous, unnoticed inner nuclear layer (INL) infarction in the fellow eye. METHODS: This prospective case-control study compared the prevalence of INL lesions in the fellow eye of consecutive people with hypertension (PwHTN) with unilateral RVO versus a randomly chosen eye of an age-matched control group of PwHTN without RVO. En face slabs above the outer plexiform layer (OPL) were generated from 6 × 6 fovea-centered optical coherence tomography scans. Cross-sectional scans and en face slabs were surveyed for evidence of active/resolved ischemic INL lesions. RESULTS: 69 PwHTN were included and assigned to two groups, i.e., the RVO group (n = 37; 22 BRVO and 15 CRVO) and the control group (n = 32). There was no inter-group difference regarding age, gender distribution, and background diseases. Resolved INL lesions were more frequent in the RVO group (n = 26) than in the control group (n = 4) (70.3% vs. 12.5%, p < 0.001). BRVO and CRVO cases had similar prevalence of INL lesions in their fellow eyes. Unlike diabetes, ischemic heart disease, and gender, INL lesions were associated with RVO (in the fellow eye) with an odds ratio of 15.7 (95%CI: 4.17-76.73, p < 0.001). CONCLUSION: We identified a substantially higher prevalence of INL lesions in PwHTN with RVO compared to PwHTN without RVO. The atrophic appearance of lesions suggests they may serve as early markers of increased RVO risk in individuals with systemic or cardiovascular predisposing factors.

Optical coherence tomography angiography parameters after cataract surgery.

PURPOSE: To evaluate the changes in macular blood flow after cataract surgery through optical coherence tomography angiography (OCT-A). METHODS: In this prospective case series, 50 patients who underwent uncomplicated cataract surgery by the resident were included. OCT-A images and complete ocular examinations were performed at baseline, 1 and 3 months postoperatively. The changes in OCT-A parameters including foveal avascular zone (FAZ) area, vessel density (VD) of superficial and deep plexus, and central macular thickness were assessed before and after surgery. Cataract grading, intraocular inflammation, and duration of surgery were analyzed. RESULTS: FAZ was significantly reduced from 0.36 ± 0.13 mm2 at baseline to 0.32 ± 0.12 mm2 at month 1 (P < 0.001) and this reduction continued until month 3. In the superficial layer, vessel density of the fovea, parafovea, and whole image significantly increased from 13.9 ± 6.8, 43.7 ± 4.7, and 43.2 ± 4.4 at baseline to 18.4 ± 7.9, 45.7 ± 4.9, and 44.9 ± 4.5 at month 1. The increase in the vessel density of the deep layer was similar to the superficial layer. Accordingly, CMT at the fovea was significantly increased from 240.5 ± 21.99 µm at baseline to 253.1 ± 23.2 microns at month 1 (P < 0.001) and the increase significantly continued and reached 259.5 ± 22.6 µm at month 3 (P < 0.001). Accordingly, the FAZ area significantly reduced one month postoperatively. In regression analysis, CMT changes positively correlated with cataract grading. FAZ area negatively correlated with intraocular inflammation on the first postoperative day. CONCLUSION: The present study shows that CMT and vessel density of the macula significantly increase after uncomplicated cataract surgery, while the FAZ area reduces. Postoperative inflammation could be the possible explanation for the findings of this study.

Retinal ischemic cascade: New insights into the pathophysiology and imaging findings.

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

RONA Technique: A Novel ILM Peeling Method for Treatment of Large Full-Thickness Macular Holes.

PURPOSE: To present a new technique, RONA, for internal limiting membrane peeling and show its comparable success rate in closure of large full-thickness macular holes (FTMHs). METHODS: This prospective interventional case series was implemented from January 2018 to November 2019. Consecutive cases with large FTMH with an aperture size of more than 500 µ m were included. The RONA technique was used to make consecutive flaps; the central border of which remained adherent to the FTMH edge. The emphasis is that the central border of all flaps should remain adherent to the FTMH edge, letting the flaps remain there spontaneously. RESULTS: Seventeen eyes of 17 patients (4 males and 13 females; age 62.3 ± 7.8 years) were included. The mean size of opening and base of FTMH were 651.1 ± 141.1 µ m (range: 501-950) and 964.6 ± 383.8 µ m (range: 527-2098), respectively. One week after the surgery, complete closure of all FTMHs occurred with no hole reopening until the end of 12 months. The mean best-corrected visual acuity at baseline and 12 months after surgery were 1.57 ± 0.30 and 0.75 ± 0.028 logarithm of the minimum angle of resolution, respectively, with statistically significant improvement ( P < 0.001). CONCLUSION: The first advantage of this efficacious technique is that there is no need to manipulate FTMH edge or underneath tissues. Another and of course, the most important advantage is that there is no need to care about flap unfolding during the exchange stage.

Optical Coherence Tomography Angiography in Patients with Amblyopia.

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

A Case of Fingolimod-associated Cryptococcal Meningitis.

BACKGROUND: Leukopenia, a rare adverse effect of Fingolimod therapy, paves the way for opportunistic infections. In this study, we reported rare fingolimod associated cryptococcal meningitis. CASE PRESENTATION: A 39-year-old woman with RRMS was referred to the emergency department. The patient's major complaints were headache, fever, weakness, and progressive loss of consciousness within the last two days prior to the referral. The patient had a history of hospitalization due to RRMS [two times]. In the second hospitalization, interferon Beta-1a was replaced with Fingolimod. Using polymerase chain reaction, Cryptococcus neoformans was detected in CSF. Liposomal amphotericin B and fluconazole [800 mg per day] were started. Six weeks later, the patient was discharged without any major complaints. CONCLUSION: Albeit fingolimod associated cryptococcal meningitis is a rare event, Fingolimod therapy in patients with MS should be performed cautiously. Regular follow-ups may give rise to a timely diagnosis of probable fingolimod associated cryptococcal meningitis. Fingolimod therapy can lead to lymphocytopenia and various infections. We, therefore, suggest that intermittent blood lymphocyte counts as well as monitoring of clinical manifestations among MS patients treated with Fingolimod to avoid additional neurological and physical disabilities in these patients.

Combined intravitreal injection of bevacizumab and a ROCK inhibitor (fasudil) for refractory macular edema secondary to retinal vein occlusion: a pilot study.

BACKGROUND: To investigate the adjunctive effect of an intravitreal ROCK inhibitor (fasudil) in combination with intravitreal bevacizumab (IVB) on refractory macular edema secondary to retinal vein occlusion (RVO). METHODS: In this prospective interventional case series, 17 eyes of 17 patients (10 men, 7 women) with refractory RVO-related macular edema underwent three consecutive intravitreal injections of bevacizumab plus fasudil. Monthly evaluation was continued up to 12 months and IVB injection was performed if needed during the follow-up. Changes in the best corrected visual acuity (BCVA) was the primary outcome measure. The secondary outcome measures included central macular thickness (CMT) changes and any adverse events. RESULTS: BCVA significantly improved (mean change: -0.15 LogMAR; P = 0.017) after 3 consecutive intravitreal injections of fasudil in combination with bevacizumab. CMT significantly decreased (mean change: -206 µm; P = 0.028). The anatomical and functional improvement was maintained during the 12 month follow-up. No adverse effects were noticed. CONCLUSION: Intravitreal ROCK inhibitors may break the resistance to anti-VEGF therapy and improve the RVO induced macular edema via affecting the VEGF-independent pathways.

PANRETINAL PHOTOCOAGULATION VERSUS INTRAVITREAL BEVACIZUMAB VERSUS A PROPOSED MODIFIED COMBINATION THERAPY FOR TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Three-Arm Clinical Trial (CTPDR Study).

PURPOSE: To compare safety and therapeutic effect of three treatment protocols on patients with naive proliferative diabetic retinopathy. METHODS: A total of 207 eyes with proliferative diabetic retinopathy were randomly divided into three groups: full panretinal photocoagulation group; intravitreal bevacizumab (IVB) group with four monthly IVB injections; and modified combination group with two bimonthly IVB injections and a modified laser therapy. The best-corrected visual acuity and area of neovascularization leakage were compared at 1-year follow-up. RESULTS: The difference in final best-corrected visual acuity was not significant between the groups (P = 0.77). The modified combination group had the lowest final leakage area (P = 0.006). The difference in final mean deviation of visual field was not significant between IVB and modified combination groups (mean difference = 0.25, P = 0.23, 95% confidence interval, 0.12-1.38). There was no difference in rate of new-onset diabetic macular edema between IVB and modified combination groups (mean difference = 1.5%, P = 0.31, 95% confidence interval, 1.1-1.88). Mean of total IVB injections were 3.5, 7.4, and 6.2 for panretinal photocoagulation, IVB, and modified combination groups, respectively (P = 0.002). Patients in the IVB group underwent more visits (P = 0.001). In subgroup analysis, the difference in the final leakage area was significant for the eyes with diabetic macular edema (P = 0.005). CONCLUSION: A combination protocol of photocoagulation and IVB can be recommended for proliferative diabetic retinopathy, especially with baseline diabetic macular edema.

Retinal Vascular Response to Hyperoxia in Patients with Diabetes Mellitus without Diabetic Retinopathy.

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

Ocular Manifestations of the Sturge-Weber Syndrome.

Sturge-Weber syndrome (SWS) or encephalotrigeminal angiomatosis is a non-inherited congenital disorder characterized by neurologic, skin, and ocular abnormalities. A somatic activating mutation (R183Q) in the GNAQ gene during early embryogenesis has been recently recognized as the etiology of vascular abnormalities in SWS. Approximately, half of the patients with SWS manifest ocular involvement including glaucoma as the most common ocular abnormality followed by choroidal hemangioma (CH). The underlying pathophysiology of glaucoma in SWS has not been completely understood yet. Early onset glaucoma comprising 60% of SWS glaucoma have lower success rates after medical and surgical treatments compared with primary congenital glaucoma. Primary angle surgery is associated with modest success in the early onset SWS glaucoma while the success rate significantly decreases in late onset glaucoma. Filtration surgery is associated with a higher risk of intraoperative and postoperative choroidal effusion and suprachoroidal hemorrhage. CH is reported in 40-50% of SWS patients. The goal of treatment in patients with CH is to induce involution of the hemangioma, with reduction of subretinal and intraretinal fluid and minimal damage to the neurosensory retina. The decision for treating diffuse CHs highly depends on the patient's visual acuity, the need for glaucoma surgery, the presence of subretinal fluid (SRF), its chronicity, and the potential for visual recovery.

Retinal Vascular Abnormalities in Different Types of Inherited Retinal Dystrophies Assessed by Optical Coherence Tomography Angiography.

PURPOSE: To investigate the retinal vascular characteristics among patients with different types of inherited retinal dystrophies (IRDs). METHODS: This comparative cross-sectional study was conducted on 59 genetically confirmed cases of IRD including 37 patients with retinitis pigmentosa (RP) (74 eyes), 13 patients with Stargardt disease (STGD) (26 eyes), and 9 patients with cone-rod dystrophy (CRD) (18 eyes). Both eyes of 50 age- and sex-matched healthy individuals were investigated as controls. All participants underwent optical coherence tomography angiography to investigate the vascular densities (VDs) of superficial and deep capillary plexus (SCP and DCP) as well as foveal avascular zone area. RESULTS: In RP, significantly lower VD in whole image (P = 0.001 for DCP), fovea (P = 0.038 for SCP), parafovea (P < 0.001 for SCP and DCP), and perifovea (P < 0.001 for SCP and DCP) was observed compared to controls. In STGD, VD of parafovea (P = 0.012 for SCP and P = 0.001 for DCP) and fovea (P = 0.016 for DCP) was significantly lower than controls. In CRD, the VD of parafovea (P = 0.025 for DCP) was significantly lower than controls. Whole image density was significantly lower in RP compared to STGD (P < 0.001 for SCP) and CRD (P = 0.037 for SCP). VD in parafovea (P = 0.005 for SCP) and perifovea (P < 0.001 for SCP and DCP) regions was significantly lower in RP compared with STGD. Also, foveal VD in STGD was significantly lower than RP (P = 0.023 for DCP). CONCLUSION: Our study demonstrated lower VDs in three different IRDs including RP, STGD, and CRD compared to healthy controls. Changes were more dominant in RP patients.

Intravitreal connective tissue growth factor neutralizing antibody or bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model.

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

Multimodal imaging for paracentral acute maculopathy; the diagnostic role of en face OCT.

BACKGROUND: To describe the features of multimodal imaging and the diagnostic role of en face OCT in the paracentral acute middle maculopathy (PAMM) spectrum. METHODS: In this observational case series, 5 eyes of 5 patients with acute PAMM were identified. Demographic characteristics as well as data regarding the underlying disease, presenting visual acuity (VA) and ophthalmic examination results were recorded. All patients underwent multimodal imaging within 3 days after symptom onset. RESULTS: The mean age of patients was 52.2 (range, 33-67) years. Systemic comorbidities including diabetes mellitus and hypertension were identified in two patients. Except for one patient diagnosed with isolated PAMM, other patients had signs of retinal vascular disease such as a cilioretinal artery or branch retinal artery obstruction, non-ischemic central retinal vein occlusion, or a combination of these vascular disorders. The central vision was preserved in two cases; however, the remaining cases presented with profound VA reduction. Different patterns of PAMM including arterial, globular, and fern-like were observed in en face OCT at deep capillary plexus (DCP) level. En face OCT images could precisely delineate the margin of the PAMM area. Optical coherence tomography angiography (OCTA) showed decreased vascular density in DCP. Unresolved projection artifact by conventional OCTA software was observed in DCP and choriocapillaris slabs in all cases. CONCLUSION: En face structural OCT in PAMM can delineate the area of ischemia and the degree of foveal involvement. Unresolved projection artifact by conventional OCTA software in the PAMM area can be seen in DCP and choriocapillaris layers.

Retinal changes in patients with angina pectoris and anginal equivalents: a study of patients with normal coronary angiography.

Background and aims. Approximately 10-30% of the patients with typical symptoms of angina pectoris have normal angiography showing normal macrovasculature. In these patients, however, the microvascular problems should be monitored. Hence, the main aim of this study is to evaluate retinal changes in normal angiographic patients.Methods. In this descriptive cross-sectional study, 60 normal angiographic patients with typical chest pain or anginal equivalents visiting Modarres Hospital Cardiology Research Center between 2018 and 2019 were enrolled and retinal changes were determined in Labbafinejad Hospital by Optical Coherence Tomography Angiography using Foveal Avascular Zone (FAZ), Superficial Vascular Density (SVD), and Deep Vascular Density (DVD).Results. The results of this study demonstrated that FAZ was normal in all subjects, but SVD and DVD were abnormal in 45% and 8.3%, respectively. Totally, 18.5% and 66.7% showed abnormal SVD among stable angina (SA) and unstable angina (UA) cases, respectively (P < 0.001). There was no statistically significant difference between abnormal DVD in SA and UA cases (P = 0.058). Abnormal SVD was significantly more common among diabetic patients (P < 0.001), while DVD was not related to diabetes presence in the study population (P > 0.05). Moreover, abnormal SVD was more common among patients with chest pain (P = 0.036), while there was no significant difference for DVD (P = 0.371). Interestingly, abnormal ECG was associated with both abnormal DVD and SVD.Conclusions. The results of this study showed that nearly half of the patients with angina pectoris or anginal equivalents who revealed normal angiographic findings may suffer from retinal changes. Thus, retinal assessment is needed in these patients to evaluate microvascular changes.