Implementation of thyroid eye disease registry in Iran: rationale and research protocol.

BACKGROUND: To describe the implementation of a registry system for patients with thyroid eye disease (TED) in Iran to obtain more information about its nature, prevalence, and annual incidence, as well as extend insight into the etiology, pathogenesis, and eventually make an accurate prognosis of different medical or surgical treatment methods. METHODS: After receiving approval from the Disease Registry Committee of Iran University of Medical Sciences (IUMS) in 2019 and the Ministry of Health and Medical Education (MOHME) in 2020, the protocol was introduced in three consecutive phases at regional, provincial and national levels. The establishment of a registry committee in Rassoul Akram Hospital, one of the medical centers affiliated to IUMS, was the first step to organizing the registry project's main core. The steering committee included six subgroups of required subject fields. The members are experts in developing a guideline, providing a new dataset, drawing an outline for the next steps, and structuring user-friendly software through several panel discussion meetings. The data is collected from clinical and para-clinical/imaging findings, laboratory evaluations, and their selected treatment strategy, retrospectively and prospectively. RESULTS: The purpose is to broaden our knowledge about the profile of TED; accordingly, data related to patients' demographics, thyroid gland disease (status, duration, treatments, and function tests), general medical and ocular history, along with visual/ocular exams resulting TED status are collected and recorded in a 2- language software. The web-based software system is accessible at https://orc.iums.ac.ir . To maintain data security, prioritized user access was defined for different members. Furthermore, diverse methods, such as employing trained staff and utilizing software validation rules, were implemented to control data quality in every step of data collection, entry, and registration. Medical records of retrospective subjects were also evaluated and entered after accuracy verification. CONCLUSION: Iran's TED registry provides practitioners with comprehensive data on natural history and phenotype variations in clinical features and outcomes. It facilitates patient recruitment and, consequently, earlier diagnosis on a large scale which helps improve treatment and quality of life for patients.

The correlation between humoral immune responses and severity of clinical symptoms in COVID-19 patients.

The SARS-CoV-2 pandemic persists with global repercussions. Initial COVID-19 symptoms encompass pneumonia, fever, myalgia, and fatigue. The human immune system produces IgM and IgG antibodies in response to SARS-CoV-2. Despite previous research, a comprehensive understanding of the interplay between clinical manifestations and humoral immune responses remains elusive. This study aims to scrutinize this association. 134 COVID-19 patients were enrolled, and stratified into mild, moderate, and severe symptom groups. Serum IgM and IgG levels were assessed thrice at one-month intervals using ELISA. The findings reveal significant elevation in serum IgG levels in moderate compared to mild cases (P < 0.001). Additionally, IgG production was significantly heightened in severe cases compared to both mild (P < 0.0001) and moderate (P < 0.05) groups. IgM and IgG levels peaked initially and diminished over time. While anti-SARS-CoV-2 antibodies are expected to confer protection, the direct correlation between IgG levels and symptom severity may arise from delayed immune activation, resulting in an intense antibody response in severe cases. Given evidence linking delayed immune function with a dysregulated innate immune response, comprehensive data collection should encompass not only serum IgG and IgM, but also early measurement of type I interferons at symptom onset. This could provide a more thorough understanding of COVID-19 progression.

Impact of COVID-19 on the patient referral pattern and conversion rate in the university versus private facial plastic surgery centers.

PURPOSE: To compare the number of referrals and conversion rate between the pandemic and pre-pandemic period. METHODS: The number of referrals and conversion rate between the 10-month pandemic (March-December 2020) and pre-pandemic (March-December 2019) were evaluated in the two university (mainly non-cosmetic) and private (mainly cosmetic) facial plastic surgery centers. Demographics and monthly number and type (cosmetic and non-cosmetic) of the referrals and surgeries were recorded from the both and cosmetic facial injections (botulinum toxin and filler) and the source of referrals (web- and non-web-based) from the private center. The conversion rate was a ratio of the number of the surgeries to the number of referrals. RESULTS: The number of referrals declined by 7.7% in the private center which was significantly higher for the non-cosmetic (26%) than the cosmetic (0.5%) referrals. It was 32% in the university center. The private center conversion rate significantly (P < 0.001) decreased for both the cosmetic (60%) and non-cosmetic (82%) procedures. It was not significantly different between the cosmetic (65%) and non-cosmetic (58%) procedures in the university center. However, the number of cosmetic facial injections (11%) and the web-based referral source (4%) increased. The recovery was better for the number of referrals (better in the private center) than the conversion rate. CONCLUSION: The fall in the conversion rate was statistically significant in the private center. While the number of referrals recovered to almost the pre-pandemic level, the conversion rates, despite recovery, remained at a lower level at the end.

A Systematic Review on the Role of Antioxidants in Thyroid Eye Disease.

Purpose: To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED). Methods: A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including in vitro) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of H2O2-dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the in vitro studies. Results: Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 in vitro studies from 1993 to 2018. While ß-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in in vitro studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial. Conclusion: While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice.

Optic Nerve Head Vessel Density Changes from Graves' Disease without TED to TED Dysthyroid Optic Neuropathy: Does Optic Nerve Head Ischemia Play a Role?

PURPOSE: To compare the retinal peripapillary capillary (RPC) vessel density (VD) between 5 groups of patients on the spectrum of thyroid eye disease (TED). METHOD: This is a prospective comparative study looking at 5 groups of patients who were consecutively included from January 2018 to March 2021. They were composed of: Healthy volunteers (39 eyes and 20 subjects), patients with Graves' disease without TED (26 eyes and 13 patients), mild TED (28 eyes and 14 patients), moderate-severe TED (30 eyes and 17 patients), and TED with dysthyroid optic neuropathy (DON) (21 eyes and 12 patients). Ocular and periocular examination, visual field indices, RPC-VD (with optical coherence tomography angiography), and retinal nerve fiber layer, and macular ganglion cell complex thickness were recorded. RESULT: An initial insignificant (0.5 < p < 0.9) rise in the peripapillary-VD (pp-VD) and whole image-VD (wi-VD) from the healthy subject to the Graves' disease without TED was followed by a significant (p = 0.001) fall in RPC-VD in different severity grades of the TED. Paired comparison between the 5 groups showed that the statistically significant fall from the Graves' disease group occurred in the moderate-severe and DON groups (0.001 ≤ p ≤ 0.04). No variable significantly affected the VD (0.08 ≤ p ≤ 0.9). A lower wi-VD and pp-VD were significantly (0.001 ≤ p ≤ 0.009) correlated with the impaired optic nerve functional and structural tests. The sensitivity and specificity of wi-VD (81% and 76%) and pp-VD (69% and 71%) for detecting the DON were statistically significant (p < 0.001). CONCLUSION: Despite an insignificant rise in the wi- and pp-VD from the healthy volunteers to the patients with Graves' disease without TED, VD showed a declining trend in the course of patients with TED, which was statistically significant in the moderate-severe TED and DON groups.

Safety of the subconjunctival injection of doxycycline in rabbits.

Purpose: To evaluate the safety of subconjunctival injection of doxycycline in rabbit eyes. Methods: Eight white New Zealand rabbits were selected. Different concentrations of 250 micrograms (µg), 500 µg, 1000 µg, and 2000 µg in 0.1 ml were prepared for subconjunctival injection. Each concentration was injected into the two eyes of each rabbit. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. All rabbits underwent ocular examination in the 1st, 3rd, and 30th day after injection. The rabbits were sacrificed 30 days after injections and the histopathological examination was performed. Results: No obvious change was detected in all four groups from the 1st day to the 3rd day after injection in terms of tearing, hyperaemia, and chemosis. There was no visible sign of inflammation or necrosis, and also no histological change in both clinical and histopathological examinations. Conclusion: Subconjunctival injection of doxycycline with different dosages of 250 to 2000 ug in 0.1cc in rabbit eyes was safe and no clinical or histological changes were observed after one month.

Intravitreal injection of a Rho-kinase inhibitor (fasudil) combined with bevacizumab versus bevacizumab monotherapy for diabetic macular oedema: a pilot randomised clinical trial.

Click here to listen to the Podcast BACKGROUND/AIMS: To compare the efficacy of combined intravitreal injection of bevacizumab and a Rho-kinase inhibitor, fasudil (intravitreal bevacizumab (IVB)/intravitreal fasudil (IVF)), with IVB alone for centre-involving diabetic macular oedema (DME). METHODS: In this prospective randomised clinical trial, 44 eyes with centre-involving DME were randomised into two groups. The combined group received three consecutive injections of IVB (1.25 mg) and IVF (50 µM/L) monthly, while the monotherapy group received only one IVB (1.25 mg) injection per month for 3 months. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared between the two groups at months 3 and 6. The primary outcome measure was the mean change in BCVA at month 6. RESULTS: Mean BCVA was significantly improved in both groups at month 3 (P<0.001), but it persisted up to month 6 only in the IVB/IVF group. Improvement of BCVA was greater in the IVB/IVF group at both time points (P=0.008, P<0.001). In the IVB/IVF and IVB groups, 54.5% versus 10% of the eyes gained≥15 ETDRS letters at month 6 (P=0.026). Between months 3 and 6, mean BCVA significantly decreased by 5±7 ETDRS letters in the IVB group (P=0.002), while no significant deterioration was observed in the IVB/IVF group. Corresponding with the BCVA changes, CMT was significantly reduced in both groups at month 3 (p=0.006, p<0.001) but this reduction sustained only in the IVB/IVF group up to month 6 (p<0.001). CONCLUSION: Adjunctive intravitreal injection of a Rho-kinase inhibitor may enhance and prolong the therapeutic effects of anti-vascular endothelial growth factor drugs for centre- involving DME.

Association of Socio-Economic Status and Visual Impairment: A Population-Based Study in Iran.

BACKGROUNDS: To assess the role of socio-economic inequality in visual impairment (VI) in Varamin district, Iran. PATIENTS AND METHODS: Using multistage cluster sampling method, 60 clusters (each with 50 subjects) were recruited and underwent clinical eye examinations. Socio-economic status (SES) was identified based on education, occupation, family assets and housing conditions that were measured at the participants' households using a semi-structured questionnaire and a two-step cluster analysis model. In addition, principal component analysis and the concentration index were used to identify the gap between high and low SES groups. RESULTS: Participants were categorized in high (522, 24.4%), moderate (974, 43.1%) and low (763, 33.7%) socio-economic levels. In these levels, the prevalence of VI was 5.9% (95% CI: 3.3 to 8.6), 10.4% (95% CI: 8.4 to 12.4), and 12.6% (95% CI: 10.1 to 15.1), respectively. The prevalence of VI in people with low SES was significantly greater than those in high SES level. The proportions of avoidable causes were relatively high in all SES levels (more than 80%) with no significant difference between different levels. CONCLUSIONS: There is significant inequality in VI prevalence in Varamin district. Avoidable causes are high in all SES groups. Therefore, community-based modalities and preventive programs with a specific notice to poorer SES groups are recommended to improve eye health in this district.

A Possible Role for LTBP2 in the Etiology of Primary Angle Closure Glaucoma.

PURPOSE: To assess the association of LTBP2 mutations with primary angle closure glaucoma (PACG). METHODS: We studied 54 unrelated patients with PACG and one individual with pseudoexfoliation accompanied with angle closure glaucoma; these consisted of 28 female and 27 male subjects aged 27 to 82 (mean, 63) years. The 36 exons and flanking intronic sequences of LTBP2 in all patients were amplified by PCR and sequenced by the Sanger protocol. The sequences were compared to LTBP2 reference sequences. A total of 100 to 400 controls aged at least 60 years old were screened for various variations. RESULTS: Out of 24 observed sequence variations, ten were in amino acid coding regions; of these four created synonymous codons while six caused amino acid changes. Based on allele frequencies, biochemical parameters, absence in control individuals, evolutionary conservation of affected amino acids, and bioinformatic predictions on the effects on protein function, it was concluded that only two mutations causing p. Gln1417Arg and p. Gly1660Trp may contribute to PACG. The p. Gly1660Trp mutation was observed in a patient with both PACG and PEX syndrome. P. Gln1417Arg had previously been reported only in a subject with POAG. CONCLUSION: LTBP2 may contribute to PACG. This finding emphasizes that there may be an overlap in the etiology of various forms of glaucoma and the overlaps likely contribute to common features in various forms of glaucoma.

Intrasubject Difference in CCT among POAG versus Normal Individuals.

PURPOSE: To evaluate intrasubject asymmetry in central corneal thickness (CCT) among patients with primary open-angle glaucoma (POAG) as compared with that of normal subjects and to determine whether the eye with thinner cornea has more severe glaucomatous visual field damage. METHODS: In this case-control study, CCT of both eyes was measured using an ultrasonic pachymeter (UP-1000; Nidek Technologies, Gamagori, Japan) among POAG patients and normal subjects. The intrasubject difference in CCT was calculated and compared between the study groups; correlations between CCT and intraocular pressure (IOP), vertical cup-to-disc ratio (VCDR), and visual field defects were also evaluated. RESULTS: A total of 62 patients with bilateral POAG and 56 normal subjects were included. There was no significant difference between the study groups in terms of age, sex, and ocular parameters except for visual acuity, IOP, and VCDR. The POAG patients demonstrated significantly greater intrasubject asymmetry in CCT (8 ± 7 µm vs. 5 ± 3 µm; p = 0.041) and a higher prevalence of significant (>10 µm) intrasubject CCT difference (30.6 vs. 5.4%; p < 0.001) as compared with normal subjects. Although each higher level of glaucomatous damage was associated with 4-µm thinner CCT, the correlation was not statistically significant (95% confidence interval, -8 to 1 µm; p = 0.117; GEE analysis). No significant correlation was observed between CCT and IOP or VCDR (p = 0.302 and 0.137, respectively). CONCLUSIONS: Patients with POAG demonstrate a larger amount of intrasubject difference in CCT as compared with normal subjects.

Biometric parameters in different stages of primary angle closure using low-coherence interferometry.

PURPOSE: To compare ocular biometric parameters using low-coherence interferometry among siblings affected with different degrees of primary angle closure (PAC). METHODS: In this cross-sectional comparative study, a total of 170 eyes of 86 siblings from 47 families underwent low-coherence interferometry (LenStar 900; Haag-Streit, Koeniz, Switzerland) to determine central corneal thickness, anterior chamber depth (ACD), aqueous depth (AD), lens thickness (LT), vitreous depth, and axial length (AL). Regression coefficients were applied to show the trend of the measured variables in different stages of angle closure. To evaluate the discriminative power of the parameters, receiver operating characteristic curves were used. Best cutoff points were selected based on the Youden index. Sensitivity, specificity, positive and negative predicative values, positive and negative likelihood ratios, and diagnostic accuracy were determined for each variable. RESULTS: All biometric parameters changed significantly from normal eyes to PAC suspects, PAC, and PAC glaucoma; there was a significant stepwise decrease in central corneal thickness, ACD, AD, vitreous depth, and AL, and an increase in LT and LT/AL. Anterior chamber depth and AD had the best diagnostic power for detecting angle closure; best levels of sensitivity and specificity were obtained with cutoff values of 3.11 mm for ACD and 2.57 mm for AD. CONCLUSIONS: Biometric parameters measured by low-coherence interferometry demonstrated a significant and stepwise change among eyes affected with various degrees of angle closure. Although the current classification scheme for angle closure is based on anatomical features, it has excellent correlation with biometric parameters.

"Planning eye health services in Varamin district, Iran: a cross-sectional study".

BACKGROUND: A recent survey of avoidable blindness in Varamin District, Iran, identified moderately high levels of visual impairment (10%) and blindness (1.5%) in people >50 years. This study aimed to define current provision, identify gaps and suggest practical solutions for improving eye health services in this area. METHODS: The World Health Organization (WHO) framework for analyzing health systems has several key components: service delivery, health workforce, information system, medical products and technologies, financing, and governance. We used this structure to investigate the strengths and weaknesses of the eye health system in Varamin. All public and private eye care facilities and a random selection of primary health care (PHC) units were assessed using semi-structured researcher-administered questionnaires. RESULTS: Varamin has 16 ophthalmic clinics, including two secondary hospitals that provide cataract surgery. There were ten ophthalmologists (1:68,000 population), two ophthalmic nurses and five optometrists working in Varamin district. There were no eye care social or community workers, ophthalmic counsellors, low vision rehabilitation staff. Although the Vision 2020 target for ophthalmologists has been met, numbers of other eye care staff were insufficient. The majority of patients travel to Tehran for surgery. The recent survey identified cataract as the leading cause of blindness, despite the availability of surgical services in the district and high health insurance coverage. Poor awareness is a major barrier. No units had a written blindness prevention plan, formal referral pathways or sufficient eye health promotion activities. Only one of the PHC units referred people with diabetes for retinal examination. There is partial integration between eye care services and the general health system particularly for prevention of childhood blindness: chemo-prophylaxis for ophthalmia neonatorum, school vision tests, measles immunization and Vitamin A supplementation. CONCLUSIONS: This analysis demonstrated the need for better integration between eye care services and the general health system, local planning for prevention of blindness, an information system, a better staff mix and health education to increase community awareness and service uptake. There is the capacity to deliver far more surgery locally. All aspects of a health system need to be developed to deliver comprehensive and efficient eye care.

Prevalence of Amblyopia and Refractive Errors Among Primary School Children.

PURPOSE: To determine the prevalence of amblyopia and refractive errors among 7 to 12-year-old primary school children in Tehran, Iran. METHODS: This population-based cross-sectional study included 2,410 randomly selected students. Visual acuity was tested using an E-chart on Yang vision tester. Refractive errors were measured by photorefractometry and cycloautorefraction. Strabismus was checked using cover test. Direct ophthalmoscopy was used to assess the anterior segment, lens opacities, red reflex and fundus. Functional amblyopia was defined as best corrected visual acuity ≤20/40 in one or both eyes with no anatomical problems. RESULTS: Amblyopia was present in 2.3% (95% CI: 1.8% to 2.9%) of participants with no difference between the genders. Amblyopic subjects were significantly younger than non-amblyopic children (P=0.004). Overall, 15.9% of hyperopic and 5.9% of myopic cases had amblyopia. The prevalence of hyperopia ≥+2.00D, myopia ≤-0.50D, astigmatism ≥0.75D, and anisometropia (≥1.00D) was 3.5%, 4.9%, 22.6%, and 3.9%, respectively. With increasing age, the prevalence of myopia increased (P<0.001), that of hyperopia decreased (P=0.007), but astigmatism showed no change. Strabismus was found in 2.3% of cases. Strabismus (OR=17.9) and refractive errors, especially anisometropia (OR=12.87) and hyperopia (OR=11.87), were important amblyogenic risk factors. CONCLUSION: The high prevalence of amblyopia in our subjects in comparison to developed countries reveals the necessity of timely and sensitive screening methods. Due to the high prevalence of amblyopia among children with refractive errors, particularly high hyperopia and anisometropia, provision of glasses should be specifically attended by parents and supported by the Ministry of Health and insurance organizations.

Prevalence of angle closure in siblings of patients with primary angle-closure glaucoma.

PURPOSE: To determine the frequency of angle closure in siblings of patients with primary angle-closure glaucoma (PACG). METHODS: In this cross-sectional observational study, siblings of consecutive patients with PACG underwent a comprehensive ophthalmologic examination, including slit-lamp biomicroscopy, measurement of intraocular pressure, stereoscopic optic nerve head examination, and dynamic gonioscopy. Ultrasonic pachymetry was obtained in all subjects; peripapillary retinal nerve fiber layer thickness measurement by optical coherence tomography and standard achromatic perimetry were performed in subjects with angle closure, categorized as primary angle-closure suspect (PACS), primary angle closure (PAC), and PACG, or any suspicion of glaucoma in the presence of open angles. RESULTS: Overall, 95 siblings from 47 families with at least 1 subject affected with PACG participated in the evaluations; 55 (57.9%) individuals were categorized within the spectrum of angle closure, including 34 (35.8%) subjects with PACS, 7 (7.4%)individuals with PAC, and 14 (14.7%) cases of PACG. Nine (9.5%) individuals with open angles demonstrated other abnormal features, these included 3 (3.2%) subjects with suspicious discs, 5 (5.3%) cases of primary open-angle glaucoma, and 1 patient (1.1%) with normal-tension glaucoma. The remaining 31 individuals (32.6%) had no evidence of glaucoma. CONCLUSIONS: Our findings indicate familial segregation of angle closure. Siblings of PACG patients are at high risk for the condition, such that two thirds of them demonstrate clinical findings related to glaucoma. These observations suggest a hereditary basis for angle closure; therefore, siblings of patients affected with angle closure should undergo targeted screening for glaucoma.

Comparison of three phakic intraocular lenses for correction of myopia.

PURPOSE: To compare the visual outcomes and complications of three different types of phakic intraocular lenses (PIOLs), for correction of moderate to high myopia. METHODS: We reviewed 112 myopic eyes undergoing PIOL implantation using Artisan (40 eyes), Artiflex (36 eyes), and implantable collamer lens (ICL, 36 eyes). Best corrected visual acuity (BCVA), intraocular pressure (IOP), pachymetry, corneal endothelial cell (CEC) loss, and higher order aberrations (HOA) were compared. RESULTS: Mean follow-up period was 30 ± 11 months. Preoperatively, spherical equivalent (SE) refractive error was -11.6 ± 3.7, -9.59 ± 1.97, and -12.3 ± 4.8 D in the Artisan, Artiflex and ICL groups, respectively. SE was comparable among the study groups at final follow-up (P = 0.237). Mean astigmatic reduction was 0.31 ± 0.72, 0.45 ± 0.62, and 0.0 ± 0.57 in the Artisan, Artiflex and ICL groups, respectively (P = 0.007). Emmetropia (±1 D) was achieved in 60%, 91.7% and 77.8% of eyes in the Artisan, Artiflex and ICL groups, respectively, the difference was significant between the Artisan and Artiflex groups (P = 0.017). BCVA improvement more than one line occurred in 25%, 19.4% and 38.9% of eyes (P = 0.158); pachymetric changes were minimal with no difference among the three groups (P = 0.754), and mean CEC loss was 10 ± 9%, 9 ± 6% and 9 ± 10% in the Artisan, Artiflex and ICL groups, respectively (P = 0.694). HOAs (P = 0.039), vertical trefoil (P = 0.032) and spherical aberration (P = 0.001) were higher with Artisan group as compared to ICL. Total aberrations (P = 0.028) and spherical aberration (P = 0.001) was also higher with Artisan group as compared to Artiflex. CONCLUSION: Visual and refractive outcomes were comparable with Artisan, Artiflex and ICL. In terms of HOAs and quality of vision, ICL and Artiflex seem to be better choices in highly myopic eyes.