Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting.

OBJECTIVE: The purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients. METHODS: Genetic testing was conducted on 2977 individuals originally referred for BRCA1 and BRCA2 hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted to PALB2 for the purposes of this study. A patient recontact decision tree was developed to assist in the returning of updated genetic test results to clinics and patients. RESULTS: Novel clinically actionable pathogenic variants were identified in the PALB2 gene in 18 participants (0.6%), the majority of whom were recontacted with their new or updated genetic test results. Eight individuals were unable to be recontacted; five individuals had already learnt about their new or updated findings from genetic testing outside the context of this study; three individuals prompted cascade testing in family members; two individuals were deceased. CONCLUSION: Novel pathogenic variants in PALB2 were identified in 18 individuals through retrospective gene panel testing. Recontacting these individuals regarding these new or updated findings had a range of outcomes. The process of conveying genomic results within this framework can be effectively accomplished while upholding patient autonomy, potentially leading to advantageous outcomes for patients and their families.

Clinical characteristics and surgical outcomes in patients with superior oblique muscle palsy: a retrospective study on 1057 patients.

BACKGROUND: To evaluate the clinical findings of patients with SOP who underwent surgery. METHODS: This historical cohort study was performed on 1057 SOP patients managed with surgery in Farabi Hospital, Iran, from 2011 to 2022. RESULTS: There were 990 (93.7%) patients with unilateral SOP with the mean age of 21.8 ± 14.8 years. Of these, 715 patients (72.2%) were diagnosed with congenital SOP, and 275 patients (27.8%) had acquired SOP (P < 0.001). In contrast, 67 (6.3%) patients were diagnosed with bilateral SOP, with the mean age of 19.4 ± 15.6 years. Among these, 18 cases exhibited the masked type. The mean angle of vertical deviation in primary position at far in unilateral and bilateral cases was 15.6 ± 8.3 and 13.3 ± 9.1 △, respectively (P < 0.001). In unilateral cases, abnormal head posture (AHP) was detected in 847 (85.5%) patients and 12 (1.2%) had paradoxical AHP. Amblyopia was found in 89 (9.9%) unilateral and 7 (10.3%) bilateral cases. Solitary inferior oblique myectomy, was the most common surgery in both unilateral (n = 756, 77.1%) and bilateral (n = 35, 52.2%) patients. The second surgery was performed for 84 (8.6%) unilateral and 33 (49.3%) bilateral cases (P < 0.001). The prevalence of amblyopia and the mean angle of horizontal deviation were significantly higher in patients who needed more than one surgery (all P < 0.05). CONCLUSION: Congenital SOP was more than twice as frequent as acquired SOP and about 90% of unilateral and 50% of bilateral cases were managed with one surgery. Amblyopia and significant horizontal deviation were the most important factors for reoperation. TRIAL REGISTRATION: The Institutional Review Board approval was obtained from the Tehran University of Medical Sciences (IR.TUMS.FNM.REC.1400.012) and this study adhered to the tenets of the Declaration of Helsinki and HIPAA.

Strabismus management in retinoblastoma survivors.

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12-84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30-60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25-50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P < 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10-24) months, in which, 3 (17%) patients needed a second surgery. CONCLUSION: Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis.

Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository.

BACKGROUND: This study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation. METHODS: Laboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin. RESULTS: Twelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants. CONCLUSIONS: The COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care.

Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.

Arsenic trioxide (ATO) and statins have been demonstrated to have anti-neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real-time PCR. Our data displayed that Simvastatin (12 and 8 µM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 µM in PC3 and LNCaP cell lines respectively), and also their combination (12 µM Simvastatin and 8 µM ATO in PC3, 8 µM Simvastatin and 5 µM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti-proliferative and anti-angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer.

Impact of germline mutations in cancer-predisposing genes on long-term survival in patients with epithelial ovarian cancer.

BACKGROUND: Several clinical and tumour factors impact on ovarian cancer survival. It is important to evaluate if germline mutations impact long-term outcomes among patients with epithelial ovarian cancer. METHODS: We followed 1422 Ontario women with ovarian cancer. Clinical information was obtained from medical records and vital status was determined by registry linkage. Germline genetic testing was performed for 12 susceptibility genes. We estimated 20-year cancer-specific survival according to various factors. RESULTS: Twenty-year survival was inferior for women with serous cancers vs. other types (22.3% vs. 68.6%; P < 0.0001). Of the 1422 patients, 248 (17.4%) carried a germline mutation; 119 BRCA1; 75 BRCA2; 7 in a mismatch repair (MMR) gene and 47 in one of seven other genes. Among serous patients, 20-year survival was 28.9% for similar for women with a BRCA1 (28.9%), BRCA2 (21.2%) or no mutation (21.6%). Among endometrioid patients, 20-year survival was poor for women with a BRCA vs. no mutation (47.3% vs. 70.4%; P = 0.004). Six of the seven MMR mutation carriers are currently alive, while all three PALB2 mutation carriers died within 3 years of diagnosis. Among women with Stage III/IV serous cancers, 20-year survival was 9.4% for those with vs. 46.5% for those with no residual disease (HR = 2.91; 95% CI 2.12-4.09, P < 0.0001). CONCLUSIONS: The most important predictor of long-term survival was no residual disease post surgery. BRCA mutation status was not predictive of long-term survival while those with MMR mutations had excellent survival. Larger studies on PALB2 carriers are needed.

The influence of alternate part-time patching on control of intermittent exotropia: a randomized clinical trial.

PURPOSE: To evaluate the effect of alternate part-time patching on deviation control in patients with intermittent exotropia in comparison to observation. METHODS: In a randomized clinical trial, untreated 3-8-year-old children with intermittent exotropia were randomly divided into patching group who treated with alternate part-time patching and observation group. Deviation control was assessed with 3-point and 6-point scales. Stereoacuity and suppression were evaluated with Titmus and Worth-4-dot tests respectively. All exams were repeated 3 and 6 months after beginning of treatment. RESULTS: Seventy-six patients (35 in patching and 41 in observation group) with a mean age of 4.99 ± 1.33 years completed the 6-month course of study. Based on 3-point scale, deviation control was significantly better in patching group after 3 and 6 months at near and after 3 months at far (p = 0.011, 0.011, and 0.03, respectively) but non-significant after 6 months at far (p = 0.16). According to 6-point scale, deviation control was also significantly better in patching group after 3 months (p = 0.03 at far, 0.003 at near) and 6 months (p = 0.03 at far, 0.003 at near). Three and 6 months stereoacuity was not significantly different between groups (p = 0.86 for both). However, there was greater stereoacuity changes among patching group in comparison with observation group from baseline to 3 and 6 months (p = 0.006 for both). CONCLUSION: Patching seems effective in improving deviation control of 3-8-year-old children with intermittent exotropia in comparison with observation based on two common office control scales. TRIAL REGISTRATION NUMBER AND DATE: NCT03700632 (10/9/2018).

Anti-Vibriocholerae IgY Antibody Inhibits Mortality in Suckling Mice Model.

BACKGROUND: Regarding to the importance of cholera in Iran and the potential advantages of egg yolk antibody (IgY) for immunotherapy, the aim of this study was to produce IgY antibody against V. cholerae Lipopolysaccharide (LPS) and determine its potential for V. cholerae treatment. METHODS: LPS was prepared, and the Anti-V. cholerae LPS IgY was purified from egg yolk and serially diluted in phosphate-buffered saline (PBS), mixed with V. cholerae and then gavaged into several groups of suckling mice. RESULTS: The yield of Anti-LPS IgY extraction was 40 mg/Egg yolk. The results demonstrated that up to approximately 75 ng of IgY can detect specifically V. cholerae. The lowest protective dose of anti-V. cholerae LPS IgY was 2.5 µg. CONCLUSIONS: The produced anti-Vibrio LPS specific IgY showed a good reactivity with its specific antigen and it may use as a complimentary oral immunotherapy for cholera disease.

Medial rectus muscle elongation, a technique to treat very large-angle esotropia.

PURPOSE: The purpose was to describe the medial rectus muscle elongation (MRE) procedure to treat very large-angle esotropia (ET) with surgery on a lower number of muscles. METHODS: Twenty patients with very large-angle ET (more than 70 PD) underwent the MRE procedure. In the MRE procedure, the muscle was split longitudinally into three parts. The wider central part was sutured with 6/0 vicryl and disinserted. The distal end of the peripheral parts (still attached to the original insertion), 7-9 mm away from the insertion, was sutured to the proximal end of the central part. At the end of the procedure, the distance of the anastomosis site from the insertion was named as the final elongation. The dose-response effect of the final elongation was calculated in bilateral MRE cases. The mean of the dose-response effect, obtained in the binocular surgery group, was used in the monocular surgery group to calculate the resection effect of lateral rectus (LR) muscle. RESULTS: Eleven patients underwent bilateral MRE and nine patients underwent unilateral MRE and LR muscle resection. The mean preoperative far and near deviation was 94.10 ± 19.33 PD. The mean postoperative deviation was 14.60 ± 18.07 PD for far and 14.50 ± 18.23 PD for near deviation. In bilateral MRE cases, the mean dose-response effect of the elongation was 5.53 ± 0.67 PD/mm for far and 5.58 ± 0.69 PD/mm for near deviation. The mean LR muscle resection effect was 6.41 ± 1.99 PD/mm for far and 6.28 ± 1.93 PD/mm for near deviation. CONCLUSION: The MRE procedure seems an acceptable method to treat very large-angle ET with surgery on a lower number of muscles.

Mutation profile of BBS genes in Iranian patients with Bardet-Biedl syndrome: genetic characterization and report of nine novel mutations in five BBS genes.

Bardet-Biedl syndrome (BBS) is a rare ciliopathy disorder that is clinically and genetically heterogeneous with 18 known genes. This study was performed to characterize responsible genes and mutation spectrum in a cohort of 14 Iranian families with BBS. Sanger sequencing of the most commonly mutated genes (BBS1, BBS2 and BBS10) accounting for ∼50% of BBS patients determined mutations only in BBS2, including three novel mutations. Next, three of the remaining patients were subjected to whole exome sequencing with 96% at 20 × depth of coverage that revealed novel BBS4 mutation. Observation of no mutation in the other patients represents the possible presence of novel genes. Screening of the remaining patients for six other genes (BBS3, BBS4, BBS6, BBS7, BBS9 and BBS12) revealed five novel mutations. This result represents another indication for the genetic heterogeneity of BBS and extends the mutational spectrum of the disease by introducing nine novel mutations in five BBS genes. In conclusion, although BBS1 and BBS10 are among the most commonly mutated genes in other populations like Caucasian, these two seem not to have an important role in Iranian patients. This suggests that a different strategy in molecular genetics diagnostic approaches in Middle Eastern countries such as Iran should be considered.

ARHGDIA: a novel gene implicated in nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome arises from a defect in the glomerular filtration barrier that permits the unrestricted passage of protein across the barrier, resulting in proteinuria, hypoalbuminaemia, and severe oedema. While most cases are due to mutations in one of five genes, in up to 15% of cases, a genetic cause is not identified. We investigated two sisters with a presumed recessive form of congenital nephrotic syndrome. METHODS AND RESULTS: Whole exome sequencing identified five genes with diallelic mutations that were shared by the sisters, and Sanger sequencing revealed that ARHGDIA that encodes Rho GDP (guanosine diphosphate) dissociation inhibitor α (RhoGDIα, OMIM 601925) was the most likely candidate. Mice with targeted inactivation of ARHGDIA are known to develop severe proteinuria and nephrotic syndrome, therefore this gene was pursued in functional studies. The sisters harbour a homozygous in-frame deletion that is predicted to remove a highly conserved aspartic acid residue within the interface where the protein, RhoGDIα, interacts with the Rho family of small GTPases (c.553_555del(p.Asp185del)). Rho-GTPases are critical regulators of the actin cytoskeleton and when bound to RhoGDIα, they are sequestered in an inactive, cytosolic pool. In the mouse kidney, RhoGDIα was highly expressed in podocytes, a critical cell within the glomerular filtration barrier. When transfected in HEK293T cells, the mutant RhoGDIα was unable to bind to the Rho-GTPases, RhoA, Rac1, and Cdc42, unlike the wild-type construct. When RhoGDIα was knocked down in podocytes, RhoA, Rac1, and Cdc42 were hyperactivated and podocyte motility was impaired. The proband's fibroblasts demonstrated mislocalisation of RhoGDIα to the nucleus, hyperactivation of the three Rho-GTPases, and impaired cell motility, suggesting that the in-frame deletion leads to a loss of function. CONCLUSIONS: Mutations in ARHGDIA need to be considered in the aetiology of heritable forms of nephrotic syndrome.

The prevalence of amblyogenic factors in children with persistent congenital nasolacrimal duct obstruction.

BACKGROUND: To evaluate the prevalence of amblyopia risk factors in children that underwent probing for persistent congenital nasolacrimal duct obstruction (CNLDO). METHODS: The medical records of children with CNLDO (after 1 year of age) that underwent probing were reviewed. Amblyopia risk factors, based on the American Association for Pediatric Ophthalmology and Strabismus referral criteria in 2013, were sought in the patientsʹ records before probing. The proportion of the patients with anisometropia >1.5 diopters (D) was separately calculated. In unilateral cases of CNLDO, sphere, astigmatism, and spherical equivalent of the eyes with CNLDO were compared with contralateral eyes in order to assess the effect of CNLDO on refractive error. In the follow-up examinations, the success of the probing or the need for additional procedures (Crawford intubation, Monoka intubation, or dacryocystorhinostomy) was evaluated. The prevalence of anisometropia between 'successful probing' and 'failed probing' groups was compared. RESULTS: A total of 433 cases were included in the study. 41 cases (9.46 %) had amblyopia risk factors. Twenty-four cases (5.5 %) had anisometropia >1.5 D (spherical or cylindrical). In unilateral cases of CNLDO, the sphere and spherical equivalent of the eyes with CNLDO were significantly greater than those of the contralateral eyes (p < 0.001 for both). Thirty-nine patients (9 %) required other interventions due to failure of probing (failed probing group). There were significantly more anisometropia prevalence in this group, compared with the successful probing group, at the initial examination (p = 0.03). CONCLUSIONS: The findings of greater prevalence of anisometropia >1.5 D (compared with the prevalence in the general population) and significantly greater sphere and spherical equivalents in the eye with CNLDO (compared with contralateral eye) in unilateral cases with CNLDO, suggested some relationships between anisometropia and long-term untreated CNLDO. The finding of more anisometropia in failed probing cases may support the theory of structural abnormality as an explanation for the possible relationship between congenital nasolacrimal duct obstruction and anisometropia.

Acute bilateral nodular scleritis following strabismus surgery in a patient with Down syndrome.

Scleritis is a rare complication of strabismus surgery. We present the case of an 11-year-old girl with Down syndrome who underwent strabismus surgery and developed bilateral symmetric nodular scleritis 3 weeks after surgery. Anterior segment optical coherence tomography revealed localized hyporeflective thickening of the sclera at the primary site of muscle insertion in both eyes. Treatment with topical and oral corticosteroids led to resolution of her condition.

Sensory exotropia versus sensory esotropia: A comparative clinical features study.

PURPOSE: This study aimed to compare the preoperative clinical features of patients with sensory esotropia (ET) and sensory exotropia (XT). METHODS: In a retrospective study, the medical records of 13,252 patients who underwent strabismus surgery were reviewed at the Farabi Eye Hospital, Iran, from 2012 to March 2022. There were 1017 patients with sensory horizontal strabismus whose, in their worse eye, had corrected distance visual acuity (CDVA) equal to or <20/160 tested with the Snellen chart. RESULTS: The mean age of patients was 29.0 ± 12.4 years [574 (56.4%) males and 443 (43.6%) females]. Sensory XT and ET were observed in 717 (70.5%) and 300 (29.5%) patients, respectively (P<.001). The mean CDVA in the strabismic and non-strabismic eyes was 1.40 ± 0.75 and 0.05 ± 0.13, respectively (P<.001). Also, the CDVA in the strabismic eyes was significantly worse in the patients with sensory XT than in the patients with sensory ET (P<.001). Sphere and spherical equivalent (SE) components were more hyperopic in both eyes of patients with sensory ET than sensory XT (P<.001). In sensory ET group, the mean horizontal deviation at far and near was significantly higher than the sensory XT group (both P<.001). The prevalence of moderate and severe amblyopia among all patients with sensory strabismus was 274 (26.9%) and 727 (71.5%), respectively (P<.001). There were 398 (39.1%) patients who needed more than one surgery. CONCLUSION: The frequency of sensory XT was about 2.5 times more than the sensory ET. Most patients with sensory ET were operated at a younger age, had better CDVA, more hyperopic spherical and SE, and higher angle of deviation compared with patients with sensory XT. The chance of reoperation in patients with sensory strabismus was about 40%.

Comparison of Cambridge vision stimulator (CAM) therapy with passive occlusion therapy in the management of unilateral amblyopia; a randomized clinical trial.

INTRODUCTION: There are limited studies on the effectiveness of Cambridge vision stimulator (CAM) therapy as a management strategy in amblyopic patients. In addition, all these studies have a low sample size. The main purpose of this study was to compare the effect of CAM therapy with passive occlusion therapy in the management of unilateral amblyopia. METHODS: In this randomized clinical trial study, 110 cooperative amblyopic children, who had not been managed previously, were randomly divided into two groups of CAM therapy (n = 55) and passive occlusion therapy (n = 55). In the CAM procedure, five discs with different spatial frequencies (SF) (2, 6, 15, 20, 30 cycles/degree) were presented to the patient (30 minutes a day, twice a week). Plates with SF equal to the two lines better than the measured corrected distance visual acuity (CDVA) were chosen. During the training, the non-amblyopic eye was occluded. The standard occlusion therapy protocols were performed in the occlusion therapy group. The CDVA for all patients was measured at baseline and then at one, two, and three months after the treatment. RESULTS: The mean age of patients in CAM and occlusion therapy groups was 7.0 ± 2.1 and 6.9 ± 1.9 years, respectively (p = .721). There was no significant difference in the mean CDVA between CAM and occlusion therapy groups after one (0.30 ± 0.16 vs. 0.25 ± 0.14, p = .079), two (0.15 ± 0.10 vs. 0.15 ± 0.11, p = .732) and three months (0.05 ± 0.08 and 0.05 ± 0.06, p = .919) from baseline. However, the mean amount of CDVA increased significantly in each follow-up in both groups (all p < .001). Regarding the amblyopia type and severity, the mean improvement of CDVA from baseline in the anisometropic patients and in moderate amblyopia was significantly higher in the CAM group than the occlusion group after two and three months (p < .05). DISCUSSION: CAM and conventional occlusion therapies significantly improved CDVA in children with amblyopia, and the difference was not significant; therefore, they could be used as alternatives. CAM therapy requires cost and time for the amblyopic patient and parents. Thus, it can be considered as a second treatment option in amblyopic patients, especially anisometropic type and moderate amblyopia, with poor compliance to patching.

The Frequency and Manifestations of Ocular Causes of Abnormal Head Posture.

PURPOSE: To determine the frequency and manifestations of different ocular causes of abnormal head posture (AHP). METHOD: This prospective, consecutive case series study was performed on 149 patients with ocular AHP at Farabi hospital, Iran, from February 2020 to June 2021. All patients underwent routine ophthalmic examinations. The manifestation of AHP was determined by direct observation from three viewing angles, while the patient read the smallest line on the vision chart that they could see. In front, above, and lateral gazes, observations were performed to find head tilt, head turn, and chin abnormal position, respectively. A picture with habitual AHP was taken from all patients. The amount of head tilt was measured by calculating the angle between the line that connects the lips center to the center of the eyebrows and the vertical line using the Corel Draw X7 computer software. RESULTS: The mean age of 149 patients with ocular AHP [101 (67.8%) males and 48 (32.2%) females] was 16.2 ± 12.2 (range, 2-57) years. The most common ocular sources of AHP were found to be superior oblique palsy (SOP) in 66 (44.3%) patients, 54 (36.2%) cases with Duane's retraction syndrome (DRS), and 12 (8.1%) patients with nystagmus. Other frequent causes of ocular AHP were dissociated vertical deviation (DVD) in 5 (3.4%), A and V pattern strabismus in 3 (2.0%), and 2 cases (1.3%) in each of Brown syndrome, inferior rectus (IR) palsy, and congenital fibrosis of the extraocular muscles (CFEOM). The most common manifestations of AHP in all cases were "pure head turn" (48.3%), followed by "pure head tilt" (24.8%), "simultaneous head tilt and head turn" (20.8%), and "chin up" (6.0%). The mean head tilt among all patients with head tilt was 10.4° ± 8.9° (range, 5.0°-31.7°). CONCLUSION: The most frequent ocular sources of AHP were SOP, DRS, and nystagmus, followed by DVD, A and V pattern strabismus, IR palsy, CFEOM, and Brown syndrome. In addition, pure head turn and pure head tilt were the most common manifestations of ocular AHP but were not always seen in the same direction or combination as previously reported with these etiologies.

Fluoxetine as a possible treatment for adult amblyopia: results of a double-blind, randomized, placebo-controlled trial.

PURPOSE: To evaluate the effects of oral fluoxetine on visual acuity and visual-evoked potential (VEP) parameters in adults with amblyopia. METHODS: In this randomized clinical trial, adults (>18 years of age) with anisometropic or strabismic amblyopia were assigned randomly to a treatment (fluoxetine) group or a placebo group. Standard treatments for amblyopia (glasses prescription and patching) were prescribed for 4 months for all patients. The first group received fluoxetine (20 mg per day) and the second group received a placebo for 3 months. Visual acuity evaluation and VEP were performed before and after treatment. RESULTS: A total of 55 participants were included: 29 in the fluoxetine group and 26 in the placebo group. Mean age was 27.2 ± 8.6 years (18-54). The mean logMAR visual acuity of the amblyopic eye improved by 0.20 ± 0.24 (0-0.8) in the fluoxetine group (P < 0.001) and by 0.08 ± 0.15 (0-0.7) in the placebo group (P = 0.01); mean logMAR improvement was significantly higher in the fluoxetine group than in the placebo group (P = 0.04). At the end of the study, mean visual acuity of the fluoxetine group (0.36 ± 0.21 log MAR) was better than the placebo group (0.43 ± 0.35 log MAR). Among the VEP parameters, N75 amplitude did not change significantly in either group relative to baseline, but the changes were statistically significantly different between the two groups (P = 0.05); N135 latency improved from baseline in the fluoxetine group (P = 0.03). CONCLUSIONS: In our study cohort, fluoxetine treatment for adult amblyopia resulted in greater improvement in visual acuity than placebo.

Internuclear Ophthalmoplegia Following COVID-19 with Abnormal Findings on Neuroimaging; A Case Report.

COVID-19 had been reported to be associated with neuro-ophthalmic complications. However, there is a shortage of evidence regarding internuclear ophthalmoplegia (INO) presentation after COVID-19 infection with related brain magnetic resonance imaging (MRI). Herein, we report a case of INO in a 69-year-old woman with presentation of diplopia following COVID-19 infection, along with her neuroimaging. We concluded that it is important to recognize the possibility of INO in patients with diplopia after COVID-19 and to consider brain MRI as an informative tool in these patients.

Refractive features and amblyopia in Duane's Retraction Syndrome: A review of the 582 patients.

PURPOSE: To report the visual and refractive characteristics and the prevalence of amblyopia in patients with different types of Duane's Retraction Syndrome (DRS). METHOD: This retrospective study was performed on hospital records of 582 DRS patients at Farabi Hospital, Iran, from 2012 to March 2022. RESULTS: The mean age of patients was 19.4 ± 11.9 (range, 3-70) years [335 (57.6 %) females and 247 (42.4 %) males (P < .001)]. DRS type I, II, III, and IV were presented in 347 (59.6 %), 148 (25.4 %), 82 (14.1 %), and 5 (0.9 %) patients, respectively. There were 530 (91.1 %) patients with unilateral and 52 (8.9 %) with bilateral involvement. In the unilateral patients, the DRS eyes' corrected distance visual acuity (CDVA) and astigmatism were significantly worse than the Non-DRS Eyes (P < .001). The mean amount of all refractive and visual parameters in bilateral patients' right or left eyes was significantly lower than in unilateral patients' non-DRS eyes (all P < .05). Anisometropia was observed in 75(12.9 %) of the patients. Amblyopia was observed in 18.5 % (98 patients) and 36.5 % (19 patients) of unilateral and bilateral DRS patients, respectively (P < .001). In unilateral patients, amblyopia was found in 57 (16.4 %) patients with Type I, 22 (14.9 %) patients with Type II, 16 (19.5 %) patients with Type III, and 3 (60 %) patients with Type IV. Forty-four (37.6 %) of patients with amblyopia had anisometropia. CONCLUSION: This large-scale study indicates that DRS types differ in terms of refractive error, visual acuity, and the prevalence of amblyopia and anisometropia. Clinicians should be aware of the clinical features associated with different types of DRS.

How Similar Are Drug Data and Disease Self-report? Estimating the Prevalence of Chronic Diseases in Less Developed Settings.

BACKGROUND: Drug data has been used to estimate the prevalence of chronic diseases. Disease registries and annual surveys are lacking, especially in less-developed regions. At the same time, insurance drug data and self-reports of medications are easily accessible and inexpensive. We aim to investigate the similarity of prevalence estimation between self-report data of some chronic diseases and drug data in a less developed setting in southwestern Iran. METHODS: Baseline data from the Pars Cohort Study (PCS) was re-analyzed. The use of disease-related drugs were compared against self-report of each disease (hypertension [HTN], diabetes mellitus [DM], heart disease, stroke, chronic obstructive pulmonary disease [COPD], sleep disorder, anxiety, depression, gastroesophageal reflux disease [GERD], irritable bowel syndrome [IBS], and functional constipation [FC]). We used sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the Jaccard similarity index. RESULTS: The top five similarities were observed in DM (54%), HTN (53%), heart disease (32%), COPD (30%), and GERD (15%). The similarity between drug use and self-report was found to be low in IBS (2%), stroke (5%), depression (9%), sleep disorders (10%), and anxiety disorders (11%). CONCLUSION: Self-reports of diseases and the drug data show a different picture of most diseases' prevalence in our setting. It seems that drug data alone cannot estimate the prevalence of diseases in settings similar to ours. We recommend using drug data in combination with self-report data for epidemiological investigation in the less-developed setting.