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.

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.

Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.

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.

Peripheral blood CD163(+) monocytes and soluble CD163 in dry and neovascular age-related macular degeneration.

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.

New criteria for evaluation of electroretinogram in patients with retinitis pigmentosa.

BACKGROUND: Electroretinogram (ERG) plays an essential role in the diagnosis of retinal disease. Choosing appropriate methods could extract valuable information from ERG. In this study, a new criterion based on time-frequency domain analysis was proposed to investigate the retina in retinitis pigmentosa (RP) patients. MATERIALS AND METHODS: The total number of 16 eyes from eight RP patients and 20 eyes from age-matched healthy subjects were assessed. The signals included photopic and scotopic ERGs. Continuous wavelet transform was applied to ERGs. Dominant frequencies were extracted, and the contours related to these dominant frequencies were selected. As a new criterion, the areas related to dominant frequency contours were considered a feature to differentiate the RP and normal groups. To better evaluate the proposed criterion results, the time-domain analysis characteristics of ERG were also considered. RESULTS: The results showed an increase in implicit time and reduced amplitude in RP patients (P < 0.05). A significant decrease of dominant frequencies and increasing their occurrence time were seen in ERG of RP patients. Also, in RP patients, the third dominant frequency was disappeared from the three main frequencies observed in photopic ERGs of normal subjects. The area criterion showed a significant decrease in RP groups (P < 0.05). CONCLUSION: RP can cause changes in the time and time-frequency components of the ERG. The area index could represent a new view of the characteristics of the ERG in the time-frequency domain. This criterion can help the ophthalmologist to have a better evaluation of retinal disease.

COL18A1 is a candidate eye iridocorneal angle-closure gene in humans.

Primary angle-closure glaucoma (PACG) is a common form of glaucoma in the Far East. Its defining feature is iridocorneal angle closure. In addition to PACG, indications of angle closure are included in the diagnostic criteria of related conditions primary angle-closure suspect (PACS) and primary angle closure (PAC). To the best of our knowledge, a causative gene for iridocorneal angle closure in humans has not been identified. This study aimed to identify the genetic cause of iridocorneal angle closure in a pedigree with at least 10 individuals diagnosed with PACS, PAC or PACG. Results of linkage analysis, segregation analysis of 44 novel variations, whole exome sequencing of 10 individuals, screenings of controls and bioinformatics predictions identified a mutation in COL18A1 that encodes collagen type XVIII as the most likely cause of angle closure in the pedigree. The role of COL18A1 in the etiology of Knobloch syndrome (KS) that is consistently accompanied by optic anomalies, available functional data on the encoded protein and the recognized role of collagens and the extracellular matrix in glaucoma pathogenesis supported the proposed role of the COL18A1 mutation in the pedigree. Subsequent identification of other COL18A1 mutations in PACS affected individuals of two unrelated families further supported that COL18A1 may affect angle closure. These PACS individuals were parents and grandparents of KS-affected children. In conclusion, a gene that affects angle closure in humans, a critical feature of PACG, has been identified. The findings also reinforce the importance of collagens in eye features and functions.

Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluation.

As vascular endothelial growth factor in choroidal neovascularization is a major cause of visual loss of the elderlies and diabetics, gene therapy may offer an alternative treatment. However, siRNA instability and inefficient delivery are the main hindrances. To address this issue, we developed a nano-sized siRNA loaded therapeutic delivery system. The chitosan-hyaluronic acid nano-polyplexes were prepared by the modified ionic gelation method. The obtained nano-polyplex with a narrow size distribution, indicated no significant cytotoxicity in the MTT test and proper cellular uptake in confocal images. The RT-PCR analysis indicated remarkable gene silencing on HUVEC cells. The intravitreally administered nano-polyplexes in rabbits overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. Intravitreal injections of the VEGFR-2 siRNA nano-polyplexes significantly reduced the size of the laser-induced choroidal neovascularization, compared to the control group. Consequently, the developed formulation can be a promising candidate for intravitreal delivery of siRNA.

Peptide selected by phage display increases survival of SH-SY5Y neurons comparable to brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a well-known neuroprotectant and a potent therapeutic candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we designed and developed BDNF-mimicking small peptides as an alternative to circumvent these problems. A phage-displayed peptide library was screened using BDNF receptor (neurotrophic tyrosine kinase receptor type2 [NTRK2]) and evaluated by ELISA. The peptide sequences showed similarity to loop2 of BDNF, they were recognized as discontinuous epitopes though. Interestingly, in silico molecular docking showed strong interactions between the peptide three-dimensional models and the surface residues of the NTRK2 protein at the IgC2 domain. A consensus peptide sequence was then synthesized to generate a mimetic construct (named as RNYK). The affinity binding and function of this construct was confirmed by testing against the native structure of NTRK2 in SH-SY5Y cells in vitro using flow-cytometry and MTT assays, respectively. RNYK at 5 ng/mL prevented neuronal degeneration of all- trans-retinoic acid-treated SH-SY5Y with equal efficacy to or even better than BDNF at 50 ng/mL.

Effects of intravitreal connective tissue growth factor neutralizing antibody on choroidal neovascular membrane-associated subretinal fibrosis.

Connective tissue growth factor (CTGF) plays an essential role in the regulation of extracellular matrix proteins and pro-fibrotic and angiogenic factors. This experimental research was conducted to evaluate if CTGF is elevated after induction of a choroidal neovascular membrane (CNVM) and whether intravitreal anti-CTGF without and with intravitreal bevacizumab (IVB) may have any effect on the CNVM associated sub-retinal fibrosis. In adherence to ARRIVE guidelines, CNVM was induced by laser spots in the right eye retinas of ninety-four pigmented rats. Quantitative real-time reverse transcription PCR (qRT-PCR) and western-blot analysis were performed on sclerochoroidal tissues of forty-four rats before and at different time intervals after laser application. The remaining fifty rats were randomly divided into five groups after laser application. Group A received intravitreal injection of 2  µl of the 50 µg/ml anti-CTGF. In group B, intravitreal injection of 2  µl of 25 mg/ml bevacizumab was performed. Group C received 1  µl intravitreal anti-CTGF and 1  µl IVB. Group D did not receive any intravitreal injection as the control group. In group E, intravitreal injection of 2  µl of nonspecific purified mouse IgG antibody was performed as the placebo group. After two weeks, double immunohistochemistry was performed by isolectin B4 and anti-collagen type1 on the sclerochoroidal flat-mounts. Masked measurement of the fluorescent images of the CNVM and CNVM associated sub-retinal fibrosis areas was performed using the image J software. Ctgf mRNA and CTGF protein levels increased to the maximum level in 24 h after laser application and remained higher than the control level up to the 14th day for the Ctgf mRNA and up to the 7th day for the CTGF protein level. Means of CNVM associated sub-retinal fibrosis areas in three treatment groups (A, B and C) were significantly less than the control (D) and placebo (E) groups (P < 0.001, <0.05, <0.001 respectively). For groups A and C, mean CNVM associated sub-retinal fibrosis areas were also significantly less than group B (P < 0.05 and < 0.01, respectively). In conclusion, this study showed significant reduction of the CNVM associated sub-retinal fibrosis via inhibition of the CTGF which mediates the final steps of fibrosis in various inflammatory and angiogenic pathways.

Combination of intravitreal bevacizumab and erythropoietin versus intravitreal bevacizumab alone for refractory diabetic macular edema: a randomized double-blind clinical trial.

PURPOSE: To evaluate the effect of three intravitreal bevacizumab (IVB) injections alone or in combination with intravitreal erythropoietin (EPO) in the treatment of refractory diabetic macular edema (DME). METHODS: In a randomized double-blind clinical trial, 48 eyes of 34 diabetic patients with refractory DME were enrolled. Eyes were randomly assigned to receive either 3 monthly injections of 0.05 cc (1.25 mg) IVB plus 0.05 cc (1000 unit) EPO or 0.05 cc (1.25 mg) IVB alone. Main outcome was best-corrected visual acuity (BCVA) changes and secondary outcome was central macular thickness (CMT). The patients were followed for 6 months. RESULTS: Mean BCVA changes up to 4 and 6 months were insignificant in both groups. It changed from 0.72 ± 0.56 logMAR at baseline to 0.74 ± 0.5 (P = 0.85) and 0.71 ± 0.44 (P = 0.40) in the combination group and from 0.48 ± 0.39 logMAR to 0.47 ± 0.35 (P = 0.48) and 0.52 ± 0.33 (P = 0.69) in the IVB alone group, at 4 and 6 months, respectively. The difference of mean BCVA changes between the groups was insignificant at both 4 and 6 months (P = 0.07 and P = 0.36, respectively). Within the group changes of mean CMT were significant only in the combination group at 4 and 6 months, from 518 ± 134 µ at baseline to 472 ± 151 to 475 ± 167 µ, respectively (P = 0.01 and P = 0.05). Corresponding changes were not significant in the IVB alone group. However, the difference between the groups was not significant at all visits (P = 0.51 and P = 0.71, respectively). CONCLUSIONS: This clinical trial demonstrated that intravitreal erythropoietin had no additional effect to IVB in the treatment of refractory DME in the short term. TRIAL REGISTRATION: Clinical trials.gov identifier: NCT03821168.

Human organotypic retinal flat-mount culture (HORFC) as a model for retinitis pigmentosa11.

The splicing factor PRPF31 is the most commonly mutated general splicing factor in the retinitis pigmentosa. We used a rapid, convenient and cost effective transfection method with an efficient PRPF31 knockdown in HORFC in order to study the effect of PRPF31 downregulation on retinal gene expressions in an ex vivo model. Modified calcium phosphate method was used to transfect HORFC by PRPF31 siRNA. Different times and doses of siRNA for transfection were assayed and optimum condition was obtained. PRPF31 mRNA and protein downregulation were assessed by qRTPCR and Western blot. The tissue viability of HORFC was measured using the MTT. ImageJ analysis on stained retinal sections by immunohistochemistry was used for thickness measurement of outer nuclear photoreceptor layer. The PRPF31 gene downregulation effects on retinal specific gene expression were analyzed by qRTPCR. A total of 50 nM of PRPF31 siRNA transfection after 63 h in HORFC, showed the optimum reduction in the level of PRPF31 mRNA and protein as shown by qRTPCR and Western blot (over 90% and 50% respectively). The PRPF31 mRNA silencing with calcium phosphate had no effect on cell viability in the period of the experiment. Thickness measurement of outer nuclear photoreceptor layer with IHC showed the significant reduction after 63 h of study (P value = 0.02). siRNA induced PRPF31 knockdown, led to reduction of retinal specific mRNA gene expression involved in phototransduction (RHO, GNAT1, RP1), photoreceptor structure (ROM1, FSCN2, CA4, SEMA4) and transcription factor (CRX) (fold change >5), after 63 h.

Pten Regulates Retinal Amacrine Cell Number by Modulating Akt, Tgfß, and Erk Signaling.

UNLABELLED: All tissues are genetically programmed to acquire an optimal size that is defined by total cell number and individual cellular dimensions. The retina contains stereotyped proportions of one glial and six neuronal cell types that are generated in overlapping waves. How multipotent retinal progenitors know when to switch from making one cell type to the next so that appropriate numbers of each cell type are generated is poorly understood. Pten is a phosphatase that controls progenitor cell proliferation and differentiation in several lineages. Here, using a conditional loss-of-function strategy, we found that Pten regulates retinal cell division and is required to produce the full complement of rod photoreceptors and amacrine cells in mouse. We focused on amacrine cell number control, identifying three downstream Pten effector pathways. First, phosphoinositide 3-kinase/Akt signaling is hyperactivated in Pten conditional knock-out (cKO) retinas, and misexpression of constitutively active Akt (Akt-CA) in retinal explants phenocopies the reduction in amacrine cell production observed in Pten cKOs. Second, Akt-CA activates Tgfß signaling in retinal explants, which is a negative feedback pathway for amacrine cell production. Accordingly, Tgfß signaling is elevated in Pten cKO retinas, and epistatic analyses placed Pten downstream of TgfßRII in amacrine cell number control. Finally, Pten regulates Raf/Mek/Erk signaling levels to promote the differentiation of all amacrine cell subtypes, which are each reduced in number in Pten cKOs. Pten is thus a positive regulator of amacrine cell production, acting via multiple downstream pathways, highlighting its diverse actions as a mediator of cell number control. SIGNIFICANCE STATEMENT: Despite the importance of size for optimal organ function, how individual cell types are generated in correct proportions is poorly understood. There are several ways to control cell number, including readouts of organ function (e.g., secreted hormones reach functional levels when enough cells are made) or counting of cell divisions or cell number. The latter applies to the retina, where cell number is regulated by negative feedback signals, which arrest differentiation of particular cell types at threshold levels. Herein, we show that Pten is a critical regulator of amacrine cell number in the retina, acting via multiple downstream pathways. Our studies provide molecular insights into how PTEN loss in humans may lead to uncontrolled cell division in several pathological conditions.

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.

Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

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.

Effect of Music During General Anesthesia on Anesthetic Consumption During Vitrectomy Surgery.

Background: Controversy remains about the positive role of music during general anesthesia and postoperative recovery. We, therefore, tested the hypothesis that intraoperative exposure to classical music reduces the propofol necessary to maintain the bispectral index (BIS) close to 50 during vitrectomy surgery. Materials and Methods: This double-blind clinical study is evaluating 50 patients undergoing vitrectomy surgery under general anesthesia. Patients were randomly assigned to music and white noise groups, and relevant sounds were played to patients after induction of anesthesia. The two groups were compared for the use of propofol as an anesthetic to maintain a BIS near 50 and for postoperative pain, anxiety, nausea, and vomiting. Results: Propofol consumption to maintain the set BIS score was much lower in the music group than in the white noise group (78.72 ± 25.76 microgram/kg/min and 117.91 ± 36.78 microgram/kg/min, respectively, P-value = 0.000). Postoperative pain scores were also much lower in the music group than in the white noise group (P-value = 0.000) and anxiety levels between these two groups did not differ (P-value = 0.870). No patient in the music group had complaints of postoperative nausea and vomiting (PONV) compared to six patients in the white noise group (P-value = 0.011). Conclusions: Listening to music during general anesthesia for vitrectomy surgery can reduce the use of anesthetics, postoperative pain, and PONV. Further, controlled studies are necessary to confirm our results.

Risk of Arrhythmia Among New Users of Hydroxychloroquine in Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.

OBJECTIVES: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE). METHODS: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow-up. We used cause-specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes. RESULTS: We identified 11,518 propensity score-matched patients with RA or SLE in each group. Over the mean follow-up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause-specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89-1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83-1.04), 0.98 (95% CI 0.87-1.11), and 0.95 (95% CI 0.84-1.07), respectively. CONCLUSION: Risk of any type of arrhythmia was not increased among new users of HCQ.

Choroidal structure investigated by choroidal vascularity index in patients with inherited retinal diseases.

PURPOSE: To evaluate the choroidal structure in patients with inherited retinal diseases (IRDs) by investigating the choroidal vascularity index (CVI). METHODS: The present study was conducted on 113 IRD patients and 113 sex- and age-matched healthy individuals. Patients' data was extracted from the Iranian National Registry for IRDs (IRDReg®). Total choroidal area (TCA) was determined between retinal pigment epithelium and choroid-scleral junction,1500 microns on either side of the fovea. Luminal area (LA) was considered as the black area corresponding to the choroidal vascular spaces, following Niblack binarization. CVI was calculated as the ratio of the LA to the TCA. CVI and other parameters were compared among different types of IRD and the control group. RESULTS: The IRD diagnosis included retinitis pigmentosa (n = 69), cone-rod dystrophy (n = 15), Usher syndrome (n = 15), Leber congenital amaurosis (n = 9), and Stargardt disease (n = 5). Sixty-one (54.0%) individuals of each of the study and control groups were male. The average CVI was 0.65 ± 0.06 in the IRD patients and 0.70 ± 0.06 in the control group (P < 0.001). Accordingly, the average of TCA and LA were 2.32 ± 0.63 and 1.52 ± 0.44 mm [1] in patients with IRDs, respectively. The measurements for the TCA and the LA were significantly lower in all subtypes of IRD (P-values < 0.05). CONCLUSION: CVI is significantly lower in patients with IRD than in healthy age-matched individuals. Choroidal changes in IRDs may be related to the changes in the lumen of the choroidal vessels rather than the stromal changes.

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.

Application of a Mapping Method in the Analysis of Electroretinogram in Patients with Retinitis Pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is a group of degenerative retinal diseases characterized by mutations in genes affecting retinal pigment epithelium (RPE) function, as well as mutations directly involving photoreceptors. This paper aims to evaluate a nonlinear method to distinguish between the RP and normal eye based on the Electroretinogram (ERG) signal. METHOD: ERG signal was recorded from 28 eyes of patients with the RP and 32 normal eyes. The ERG signal consists of four different stimuli, including two dark-adapted and two light-adapted stimuli. The time-domain analysis includes the amplitude and implicit time to consider the robustness of the nonlinear method. A parabolic mapping method was performed, and two criteria (Theta angle and density) extracted from the parabola were compared for both groups. RESULTS: The results showed that a-wave's amplitude and implicit time significantly changed in the dark- and light-adapted stimuli. The amplitude of the b-wave showed significant changes in all stimuli. However, the implicit time of b-wave had a significant increase only in the dark-adapted 3.0 ERG. Both nonlinear criteria showed significant changes in the RP group for all the stimuli. The p-values of dark-adapted 3.0 (p = .0121), dark-adapted 10.0 (p = .0014), light-adapted 3.0 (p = .0119), and flicker 30 Hz (p = .0323) showed significant differences. Using the density criterion, the statistical test demonstrated a significant difference between the RP and healthy normal group in dark-adapted 3.0 (p = .0076), dark-adapted 10.0 (p = .0024), light-adapted 3.0 (p = .0021), and flicker 30 Hz (p = .0165). CONCLUSION: The proposed features have made it possible to distinguish between healthy and RP eyes. This method might be helpful in early diagnosis.

Vision-Related Quality of Life in Patients with Inherited Retinal Dystrophies.

Purpose: To evaluate the effect of inherited retinal dystrophies (IRDs) on vision-related quality of life (VRQoL) among IRDs' patients in Iran. Methods: This cross-sectional study was conducted on 192 patients with different types of IRDs who were randomly selected from registered patients in the Iranian National Registry for Inherited Retinal Dystrophy (IRDReg®). All ophthalmic findings were collected based on the recorded data in IRDReg®. Moreover, the eligible participants were interviewed to fill out the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) to assess their VRQoL. Ordinal logistic regression was used to evaluate the possible association of the different clinical and nonclinical factors such as demographic information, socioeconomic status, and visual function with VRQoL. Results: The overall mean of a composite score of VRQoL was 45. All subscales obtained from the NEI VFQ-25 questionnaire except general health, mental health, and ocular pain had a significant negative correlation with logMAR best corrected visual acuity (BCVA) and near visual acuity variables. There was a statistically significant relationship between VRQoL and factors like age (odds ratio [OR] = 0.91, 95% confidence interval [CI]: 0.87-0.94), employment status (OR = 1.37, 95% CI: 1.05-4.74), logMAR BCVA (OR = 0.31, 95% CI: 0.19-0.49) and normal color vision (OR = 1.92, 95% CI: 1.74-5.01). Conclusion: The VRQoL of patients with IRDs in this study was low. BCVA could be an indicator to show VRQoL.