Diagnosis and Treatment of Lacrimal Gland Prolapse: A Narrative Review.

BACKGROUND: Lacrimal gland prolapse (LGP) is considered to be one of the causes for upper eyelid contour abnormality that should be recognized and treated properly to yield satisfactory outcomes in blepharoplasty. To describe current findings about the prevalence, pre- and intraoperative diagnosis of LGP and its treatment options. METHODS: PubMed and Google Scholar were thoroughly searched for articles published describing the diagnosis and treatment of LGP. RESULTS: The reported prevalence of LGP by various authors varies between 10 and 60% based on their preoperative or intraoperative reports. Techniques such as dacryoadenopexy, modified dacryoadenopexy, and dacryoplasty have been described to secure the prolapsed lacrimal gland back into its original position. Additionally, creating a Whitnall's barrier has also been suggested as a method to reposition the gland. While all these surgical procedures have shown promising immediate results, there is a lack of published data on their long-term outcomes. CONCLUSION: Diagnosis and proper treatment of LGP could enhance the cosmetic results of upper eyelid blepharoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Superior Oblique Muscle Extramedullary Plasmacytoma in a Patient with Multiple Myeloma and a Review of Literature.

Introduction: Multiple myeloma (MM), a plasma cell malignancy, is a systemic disease affecting various body organs. Plasmacytoma of bone and extramedullary disease (EMD) are presentations of MM. EMD is usually the sign of a more aggressive form of the disease. Herein, we report a patient with refractory MM presenting with extramedullary plasmacytoma in the superior oblique (SO) muscle. Case Presentation: A 51-year-old female presented complaining of gradual protrusion of the left eye and ocular pain from 20 days prior. She received bone marrow transplantation 1 year prior and was on a chemotherapy regimen for MM for the past 1 year. Ocular examination revealed proptosis of the left eye and mild limitations of adduction and elevation. Orbital magnetic resonance imaging demonstrated remarkable enlargement of the left SO muscle with focal contrast enhancement. The patient underwent a biopsy and mass debulking. The histopathologic exam revealed fibromuscular tissue containing a neoplasm composed of sheets of plasmacytoid cells in a varying degree of differentiation with intervening scantly vascularized stromal components. The plasmacytoid cells were diffusely positive for a cluster of differentiation 138 (CD138), leading to a diagnosis of EMD involving the EOM and soft tissue of the orbit. The patient underwent palliative radiotherapy and a systemic workup. The PET-CT scan revealed involvement of the pelvic bone and left calf. Accordingly, the chemotherapy regimen was upgraded to reflect the aggressive nature of the disease. In the last follow-up, there was no sign of tumor reactivation in the orbital soft tissues. Unfortunately, the patient succumbed to her illness 7 months following her most recent presentation. Conclusion: Early recognition of disease recurrence is lifesaving in MM patients; ophthalmic manifestations should be seriously considered as a sign of MM activity.

Diet quality indices and their relationship with dyslipidemia in adults: A cross-sectional study.

INTRODUCTION: Food habits may influence a range of modifiable risk factors of cardiovascular diseases (CVDs) including dyslipidemia. This study was conducted to find whether healthy eating index (HEI) and dietary quality index-international (DQI-I) were associated with the risk of dyslipidemia among the Iranian adults in Shiraz. METHOD: In this study, 236 participants with the age of 20-50 years were recruited from Shiraz medical centers through random cluster sampling. The HEI-2015 and DQI-I scores were computed using dietary intakes based on a 168-item food frequency questionnaire (FFQ). Logistic regression was utilized to estimate the relation between HEI-2015 and DQI-I score and lipid profile. RESULTS: Individuals in the greatest adherence to the HEI-2015 was associated with reduced odds ratio (OR) of total cholesterol (TC) and low-density lipoprotein (LDL) in the crude model (OR: 0.46 and OR: 0.30). This association was significant after adjustment for potential confounders (OR: 0.40 and OR: 0.31). Also, we observed significant association between DQI-I with TC and LDL in crude model (OR: 0.42 and OR: 0.45). In the adjusted model, participants in the last tertile of DQI-I were 55%, 58% and 57% less likely to have abnormal TC (OR: 0.45), LDL (OR: 0.42) and high-density lipoprotein (HDL) (OR: 0.43), compared those in the first tertile. CONCLUSION: In conclusion, higher adherence to DQI-I score was related to lower LDL and total cholesterol and higher HDL levels. Furthermore, in participants with higher adherence of HEI-2015 score, LDL and total cholesterol level were lower.

Tissue Extract from Brittle Star Undergoing Arm Regeneration Promotes Wound Healing in Rat.

This study set out to evaluate the wound healing properties of brittle star extracts in vitro and in vivo. Due to the great arm regeneration potential of the brittle star, Ophiocoma cynthiae, the present study aimed to evaluate the wound healing effect of hydroalcoholic extracts of brittle star undergoing arm regeneration in wound healing models. The brittle star samples were collected from Nayband Bay, Bushehr, Iran. After wound induction in the arm of brittle stars, hydroalcoholic extracts relating to different times of arm regeneration were prepared. The GC-MS analysis, in vitro MTT cell viability and cell migration, Western blot, and computational analysis tests were performed. Based on the in vitro findings, two BSEs were chosen for in vivo testing. Macroscopic, histopathological and biochemical evaluations were performed after treatments. The results showed positive proliferative effects of BSEs. Specifically, forty-two compounds were detected in all groups of BSEs using GC-MS analysis, and their biological activities were assessed. The MTT assay showed that the 14 d BSE had a higher proliferative effect on HFF cells than 7 d BSE. The cell migration assay showed that the wound area in 7 d and 14 d BSEs was significantly lower than in the control group. Western blot analysis demonstrated an increase in the expression of proliferation-related proteins. Upon the computational analysis, a strong affinity of some compounds with proteins was observed. The in vivo analysis showed that the evaluation of wound changes and the percentage of wound healing in cell migration assay in the 7 d BSE group was better than in the other groups. Histopathological scores of the 7 d BSE and 14 d BSE groups were significantly higher than in the other groups. In conclusion, the hydroalcoholic extract of O. cynthiae undergoing arm regeneration after 7 and 14 days promoted the wound healing process in the cell and rat skin wound healing model due to their proliferative and migratory biological activity.

Association between ultra-processed foods intake with lipid profile: a cross-sectional study.

The purpose of this cross-sectional study was to examine the association between ultra-processed foods (UPFs) intake and lipid profile in Iranian people. The study was performed on 236 individuals with the age range of 20-50 years in Shiraz, Iran. Food intakes of the participants were evaluated using a 168-item food frequency questionnaire (FFQ) which was previously validated in Iranian populations. In order to estimate the ultra-processed foods intake, classification of NOVA food group was used. Serum lipids including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. The results showed that mean of age and body mass index (BMI) of the participants were 45.98 years and 28.28 kg/m2, respectively. Logistic regression was used to evaluation the relation between UPFs intake and lipid profile. Higher UPFs intake was associated with increased OR of TG and HDL abnormality in both crude (OR 3.41; 95% CI 1.58, 7.34; P-trend = 0.001 and OR 2.99; 95% CI 1.31, 6.82; P-trend = 0.010) and adjusted models (OR 3.69; 95% CI 1.67, 8.16; P-trend = 0.001 and OR 3.38 95% CI 1.42, 8.07; P-trend = 0.009). But, there were no association between UPFs intake and other indices of lipid profile. Also, we found significant associations between UPFs intake and dietary nutrient profiles. In conclusion, UPFs consumption could worsen the nutritional profile of the diet and lead to negative changes in some indices of the lipid profile.

Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder.

PURPOSE: Developmentally regulated Guanosine-5'-triphosphate-binding protein 1 (DRG1) is a highly conserved member of a class of GTPases implicated in translation. Although the expression of mammalian DRG1 is elevated in the central nervous system during development, and its function has been implicated in fundamental cellular processes, no pathogenic germline variants have yet been identified. Here, we characterize the clinical and biochemical consequences of DRG1 variants. METHODS: We collate clinical information of 4 individuals with germline DRG1 variants and use in silico, in vitro, and cell-based studies to study the pathogenicity of these alleles. RESULTS: We identified private germline DRG1 variants, including 3 stop-gained p.Gly54∗, p.Arg140∗, p.Lys263∗, and a p.Asn248Phe missense variant. These alleles are recessively inherited in 4 affected individuals from 3 distinct families and cause a neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature, and craniofacial anomalies. We show that these loss-of-function variants (1) severely disrupt DRG1 messenger RNA/protein stability in patient-derived fibroblasts, (2) impair its GTPase activity, and (3) compromise its binding to partner protein ZC3H15. Consistent with the importance of DRG1 in humans, targeted inactivation of mouse Drg1 resulted in preweaning lethality. CONCLUSION: Our work defines a new Mendelian disorder of DRG1 deficiency. This study highlights DRG1's importance for normal mammalian development and underscores the significance of translation factor GTPases in human physiology and homeostasis.

Dietary Antioxidant Capacity Indices are Negatively Correlated to LDL-Oxidation in Adults.

Introduction: Former research studies have demonstrated controversial associations between dietary indices and oxidative stress biomarkers including oxidized low-density lipoprotein (ox-LDL) and malondialdehyde (MDA). So, in this cross-sectional study, we aimed to assess the association of dietary total antioxidant capacity (DTAC), oxidative balance score, and phytochemical index (PI) with ox-LDL/MDA in a healthy adult population of Shiraz, Iran. Methods: 236 individuals participated in this cross-sectional study. DTAC, OBS, and PI were calculated using a 168-item food frequency questionnaire (FFQ), which was previously validated in Iran. We measured ox-LDL and MDA in blood samples of the participants using commercially existing kits. Crude and adjusted models of linear regression were used to evaluate the relation of dietary indices with ox-LDL and MDA. Results: There was a significant association between ox-LDL and DTAC in both crude (ß = -1.55; 95% CI: -2.53, -0.58; P-trend = 0.002) and adjusted (ß = -1.65 95% CI: -2.66, -0.64; P-trend = 0.001) models. Also, a negative association was observed between ox-LDL and PI in the crude (ß = -1.26 95% CI: -2.33, -0.29; P-trend = 0.01) and adjusted (ß = -1.36 95% CI: -2.38, -0.34; P-trend = 0.01) models. Conclusion: Results of this study showed that DTAC and PI were inversely associated with ox-LDL as markers of lipid peroxidation. But no correlations were seen between MDA and dietary antioxidant indices.

QUS characteristics in Normal Population: a Mini Review and our experience.

Objectives: Quantitative ultrasound (QUS) is a bone densitometry method that is less expensive and more portable than DXA. It is also noninvasive. QUS parameters include speed of sound (SOS), broad band ultrasound attenuation (BUA), and stiffness index (SI). This study defined normal values of QUS parameters in Iranian men and women. Methods: QUS of heels measured in 258 Iranian men and women, aged 20-76 y/o. They were participants of Iranian Multicenter Osteoporosis study (IMOS), selected by randomized sampling. QUS device was an Achilles+ (GE-Lunar) device. Results: Percentiles of SI (2.5%, 50%, and 97.5%) determined. We found a good agreement between the Iranian reference values and western reference (used by device) value in defining normal and osteoporotic people (κ = 0.875). Conclusion: Results from this study suggest that QUS of the heel may be a good method for diagnosis of low bone mass in different regions.

Identification of a TPP1 Q278X Mutation in an Iranian Patient with Neuronal Ceroid Lipofuscinosis 2: Literature Review and Mutations Update.

Neuronal ceroid lipofuscinoses type 2 (CLN2), the most common form of Batten disease, is caused by TPP1 loss of function, resulting in tripeptidyl peptidase-1 enzyme deficiency and cerebral accumulation of lipopigments. Clinical hallmarks include epileptic seizures, vision loss, progressive movement disorder, ataxia, and eventually death. Diagnosis is often delayed due to the rarity of the conditions. Results: Here, we report a case presenting with clinical features of CLN2, carrying a homozygous novel nonsense variant in TPP1 (NM_000391:c.C832T, (p.Q278*), rs1352347549). Moreover, we performed a comprehensive literature review regarding previously identified disease-causing TPP1 mutations and genotype-phenotype correlations. Conclusion: Depending on the type of mutation, different phenotypes are observed in patients with CLN2, suggesting that the severity of phenotypes is related to the genotype of the patients.

High detection rate for disease-causing variants in a cohort of 30 Iranian pediatric steroid resistant nephrotic syndrome cases.

Background: Steroid resistant nephrotic syndrome (SRNS) represents a significant renal disease burden in childhood and adolescence. In contrast to steroid sensitive nephrotic syndrome (SSNS), renal outcomes are significantly poorer in SRNS. Over the past decade, extensive genetic heterogeneity has become evident while disease-causing variants are still only identified in 30% of cases in previously reported studies with proportion and type of variants identified differing depending on the age of onset and ethnical background of probands. A genetic diagnosis however can have implications regarding clinical management, including kidney transplantation, extrarenal disease manifestations, and, in some cases, even causal therapy. Genetic diagnostics therefore play an important role for the clinical care of SRNS affected individuals. Methodology and results: Here, we performed NPHS2 Sanger sequencing and subsequent exome sequencing in 30 consanguineous Iranian families with a child affected by SRNS with a mean age of onset of 16 months. We identified disease-causing variants and one variant of uncertain significance in 22 families (73%), including variants in NPHS1 (30%), followed by NPHS2 (20%), WT1 (7%) as well as in NUP205, COQ6, ARHGDIA, SGPL1, and NPHP1 in single cases. Eight of these variants have not previously been reported as disease-causing, including four NPHS1 variants and one variant in NPHS2, ARHGDIA, SGPL1, and NPHP1 each. Conclusion: In line with previous studies in non-Iranian subjects, we most frequently identified disease-causing variants in NPHS1 and NPHS2. While Sanger sequencing of NPHS2 can be considered as first diagnostic step in non-congenital cases, the genetic heterogeneity underlying SRNS renders next-generation sequencing based diagnostics as the most efficient genetic screening method. In accordance with the mainly autosomal recessive inheritance pattern, diagnostic yield can be significantly higher in consanguineous than in outbred populations.

Association between plant and animal proteins intake with lipid profile and anthropometric indices: A cross-sectional study.

BACKGROUND: Results of studies on the effects of plant and animal proteins on lipid profile are controversial. So we aimed to assess the relationship between plant and animal protein intake with lipid profile and novel anthropometric indices in healthy individuals. METHOD: In this cross-sectional study, 236 participants have selected from Shiraz medical centers (Iran) through random cluster sampling. Food intakes were assessed using a 168-items food frequency questionnaire (FFQ). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were measured. Anthropometric indices including a body shape index (ABSI), abdominal volume index (AVI), buddy roundness index (BRI), and conicity index (CI) were calculated. RESULTS: In the crude and fully adjusted models, more consumption of plant proteins was associated with TG levels (OR = 2.31; 95% CI: 1.08, 4.95; P = 0.03 and OR = 2.39; 95% CI: 1.03, 5.15; P = 0.04). Also, there was a significant direct association between plant proteins and BRI in the curd model (OR = 3.55; 95% CI: 1.32, 9.54; P = 0.01), and after adjusting for age and energy intake (OR = 3.32; 95% CI: 1.21, 9.14; P = 0.01). More consumption of plant proteins was related to higher CI in the crude model (OR = 3.06; 95% CI: 1.12, 8.31; P = 0.03), but not in the fully adjusted model. CONCLUSION: We found that a higher intake of plant proteins was associated with a higher TG level, BRI, and CI index. However, more research is needed to confirm these relations and provide the evidence needed to exert these findings into clinical practice.

Facial and Abducens Nerve Palsies Following COVID-19 Vaccination: Report of Two Cases.

A broad spectrum of neurological side effects has been reported after immunisation for COVID-19, including functional neurological disorders, cerebral vascular events, cerebral venous thrombosis, intracerebral haemorrhage, neuroleptic malignant syndrome, cranial nerve palsies, and otologic manifestations. Multiple cranial neuropathies have also been reported following vaccination in which involvement of VII nerve is the most prevalent, followed by the VI, III, and IV nerves. We describe two male patients, one with with facial nerve palsy and the other with abducens nerve palsy following COVID-19 vaccination. The patient with facial nerve palsy received the AstraZeneca vaccine 2 days before the symptoms began. In contrast, the patient with the abducens palsy had received his first dose of the Sinopharm vaccine 7 days previously. Both patients demonstrated a gradual recovery within the next 2 months. Further studies are required to investigate the proper relationship between cranial nerve palsies and vaccinations.

Trend of tendency to critical thinking among medical students in Tehran University of Medical Sciences, 2010-2015: A longitudinal study.

BACKGROUND: Critical thinking is one of the goals of education. It is a criterion for academic accreditation in medical education by concentration on students' soft skills. Due to lack of basic information on critical thinking tendency in undergraduate medical program, this study aimed to determine the trend of tendency toward critical thinking of medical students in two phases: basic science (year 1) and preinternship (year 5) at Tehran University of Medical Sciences. MATERIALS AND METHODS: This longitudinal descriptive-analytic study has been conducted in two phases (2010 and 2015); all 105 medical students were selected by accessible sampling method. Years of entrance to college was the inclusion criterion. The psychometric properties of The California Critical Thinking Dispositions Inventory (CCTDI) were confirmed, and then, the instrument was completed twice by participants. Data were analyzed by SPSS: 16 using student t-test, and paired t-tests. RESULTS: There was a significant difference between genders of students (P < 0.05). Males were more disposed toward critical thinking than females. The significant increase was found between mean of truth-seeking in the second test compared to the first test; instead, the mean of inquisitiveness, analyticity and self-confidence and inquisitiveness was significantly decreased (P < 0.05). However, in other subscales, there were no significant differences between the 1st and the 5th year students (P > 0.05). The total score of the test in the second phase was lower than the first phase, which was not significant. CONCLUSION: According to the findings, there is necessary to consider the critical thinking dispositions in medical students training programs and break down the barriers. Tendency toward critical thinking seems to be as prerequisite of critical thinking skills in undergraduate medical program.

Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome.

BACKGROUND: Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date. RESULTS: Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3. Further, we have collected COL9A3 genotype-phenotype associations from the literature. CONCLUSION: Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function.

The associations between dietary patterns and cardiovascular risk factors among adults: A cross-sectional study.

OBJECTIVE: Cardiovascular diseases (CVDs) are the major causes of death, worldwide. Although for decades the associations between individual foods and nutrients and CVDs have been investigated, little attention has been paid to dietary patterns. Therefore, this study was conducted to examine the association between dietary patterns and CVD risk factors among Iranian adults. METHODS: This cross-sectional study was performed on 236 adults who attended public health centers. Dietary intakes were collected using a valid food frequency questionnaire. Sociodemographic characteristics, anthropometric measures, and biochemical biomarkers were measured using standardized methods. Dietary patterns derived using the factor analysis. Logistic regression assessed the odds of CVD risk factors across tertiles of data-driven dietary patterns. RESULTS: We identified three dietary patterns. After adjusting for possible confounders, we observed that participants in the third category of the healthy dietary pattern (HDP) had lower odds of low HDL-C (OR = 0.26; 95% CI: 0.10-0.64) compared to those in the first category. Adherence to the mixed pattern was associated with increased odds of high serum TC in men only (OR = 3.69; 95% CI: 1.06-12.81). However, women with higher adherence to the Western dietary pattern (WDP) had higher odds of high serum TG (OR = 5.61; 95% CI: 1.69-18.59), and those with a greater adherence to HDP had lower odds of low HDL-C (OR = 0.25; 95% CI: 0.07-0.98). CONCLUSION: This study showed that adherence to HDP may protect against a low level of HDL-C, whereas mixed and Western-type diets may contribute to high serum TG levels. Future longitudinal studies are needed to assess the potential causality of the observed associations.

The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study.

BACKGROUND: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report. METHODS: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations. RESULTS: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals. CONCLUSION: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease.

An analysis of factors associated with graft topographic outcomes after deep anterior lamellar keratoplasty.

PURPOSE: To investigate the correlations between preoperative, operative, and postoperative factors and corneal graft topographic parameters after deep anterior lamellar keratoplasty (DALK) performed in keratoconus-affected eyes. METHODS: This prospective, interventional study enrolled 44 eyes. Graft topographic parameters, including keratometric astigmatism and the surface regularity index (SRI), were assessed after complete suture removal. Univariate analyses were used to evaluate the effects of preoperative factors (donor quality, donor and recipient age, keratoconus severity), operative factors (graft size, donor button roundness, roundness and centration of the donor-recipient junction), and postoperative factors (time point of suture removal) on postoperative topographic parameters. RESULTS: The roundness of the donor-recipient junction after complete suture removal had a significant association with the roundness of the donor button after trephination (P = 0.04) and the amount of graft decentration relative to the limbus (P = 0.03). A significant correlation was found between the value of graft decentration relative to the limbus and postoperative keratometric astigmatism (P = 0.001) and between the roundness of the donor-recipient junction and the postoperative SRI (P = 0.02). The flat axis of the keratometric astigmatism and the longer axis of the graft lay in the direction of graft displacement. Other investigated factors had no significant association with postoperative topographic indices. CONCLUSION: Graft displacement relative to the limbus and roundness of the donor-recipient junction were the main predictors of graft astigmatism and regularity, respectively, after DALK. Noncircularity of the donor button after trephination could increase the graft surface irregularity indirectly by influencing the roundness of the surgical wound.

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.

Outcomes of big-bubble deep anterior lamellar keratoplasty for pediatric keratoconus.

PURPOSE: To evaluate the outcomes and complications of deep anterior lamellar keratoplasty (DALK) performed for pediatric keratoconus. METHODS: This retrospective study enrolled 44 consecutive eyes of 39 keratoconus-affected children (≤ 18 years of age). All patients underwent big-bubble DALK from March 2004 to June 2016. The outcome measures included postoperative best spectacle-corrected visual acuity (BSCVA), manifest refraction, keratometry readings, and complications. RESULTS: The mean participant age was 16.8 ± 1.4 years, and the mean follow-up period was 68.5 ± 39.9 months. Successful big bubble was achieved in 33 eyes (75.0%), while the surgical technique was predescemetic DALK in 11 (25.0%). The mean BSCVA changed from 1.34 ± 0.49 LogMAR preoperatively to 0.24 ± 0.10 LogMAR postoperatively (P < 0.001). The mean keratometry decreased from 59.54 ± 5.17 D preoperatively to 46.23 ± 2.17 D postoperatively (P < 0.001). The complications encountered during the study period were intraoperative Descemet's membrane perforation (n = 5, 11.4%), the Urrets Zavalia syndrome (n = 1, 2.3%), graft epithelial problems (n = 3, 6.8%), subepithelial graft rejection (n = 5, 11.4%), high intraocular pressure (n = 8, 18.2%), and traumatic wound dehiscence (n = 2, 4.6%). Suture-related complications included premature loosening (n = 13, 29.6%), broken sutures (n = 12, 27.3%), suture-tract vascularization (n = 6, 13.6%), suture-associated abscesses (n = 5, 11.4%), and suture cheese wiring (n = 2, 4.6%). A clear graft was found in 40 eyes (90.9%) at the last follow-up examination. CONCLUSION: This study showed promising results with big-bubble DALK in keratoconus-affected children. A frequent and close follow-up with dedicated parental involvement is essential for the early recognition and management of postoperative complications.