INTS13 variants causing a recessive developmental ciliopathy disrupt assembly of the Integrator complex.

Oral-facial-digital (OFD) syndromes are a heterogeneous group of congenital disorders characterized by malformations of the face and oral cavity, and digit anomalies. Mutations within 12 cilia-related genes have been identified that cause several types of OFD, suggesting that OFDs constitute a subgroup of developmental ciliopathies. Through homozygosity mapping and exome sequencing of two families with variable OFD type 2, we identified distinct germline variants in INTS13, a subunit of the Integrator complex. This multiprotein complex associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. We determined that INTS13 utilizes its C-terminus to bind the Integrator cleavage module, which is disrupted by the identified germline variants p.S652L and p.K668Nfs*9. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Accordingly, its knockdown in Xenopus embryos leads to motile cilia anomalies. Altogether, we show that mutations in INTS13 cause an autosomal recessive ciliopathy, which reveals key interactions between components of the Integrator complex.

Effects of Smoking on Outcomes of Anti-Vascular Endothelial Growth Factor Therapy in Patients with Diabetic Macular Edema: A Retrospective Case-Control Study.

PURPOSE: To determine the effect of smoking on the response to anti-vascular endothelial growth factor (anti-VEGF) therapy treatment in patients with diabetic macular edema (DME). METHODS: This is a retrospective case - control study that included 60 eyes with DME. Smoking habits were obtained from hospital records and patient recall. Patients were divided into two groups: the ever-smoker group and the never-smoker group. All patients received Intravitreal ranibizumab with three loading doses followed by PRN protocol and all were followed up for at least 1 year. Outcome measures were best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, and number of visits. RESULTS: Smoking was not associated with worse posttreatment visual acuity and was not found to influence the change in ocular coherence tomography measurement of central macular thickness and the change in BCVA (posttreatment minus pretreatment). There were no statistically significant differences in the duration of treatment or number of visits between two groups of patients the ever-smoker group and the never-smoker group (P > 0.05). CONCLUSION: In this study, smoking status did not influence the treatment outcome of anti-VEGFs; however, smoking should be encouraged due to its well-known other systemic unwanted effects.

Association Between Keratoconus and Shoulder Dislocation: A Cross-Sectional Study.

Introduction Few studies have highlighted the correlation between shoulder dislocation and keratoconus (KC). This study aimed to examine the association between KC and shoulder dislocation using patients with KC and matched controls. Methods This cross-sectional study was conducted at Jordan University Hospital. We included patients diagnosed with KC from Jordan University Hospital's Ophthalmology Department between 2015 and 2018. We also included age- and sex-matched controls recruited randomly from fitness centers and shopping malls. All participants had complete ophthalmic and orthopedic assessments. KC was diagnosed by clinical examination followed by Pentacam (Scheimpflug Images, Oculyzer, WaveLight, Alcon, USA) confirmation. Results A total of 238 patients, with a mean age of 29.53 (±11.20) years, were included in this study. They were 144 (60.5%) men and 94 (39.5%) women. Moreover, 120 (50.4%) had KC while 118 (49.6%) did not have KC. Only 11 (4.6%) patients had previous shoulder dislocation. We did not find a significant difference in the frequency of shoulder dislocation between patients with and without KC (p = 0.512). Conclusion This study provides further evidence on the lack of association between shoulder dislocation and KC, an association that was presumed due to shared collagen characteristics.

Clinical and technical determinants of positive temporal artery biopsy: a retrospective cohort study.

Temporal artery biopsy (TAB) is one of the diagnostic tools to confirm the diagnosis of giant cell arteritis (GCA). We aim to evaluate the clinical and technical determinants of a positive biopsy. Demographics, clinical, technical, and laboratory data of all TAB's performed between 2007 and 2019 at a single academic medical center. 107 biopsies performed for 103 patients were included; 72.9% were female, and 27.1% were male. The mean age at the time of biopsy was 67.1 ± 9.3 years. One biopsy was excluded for lack of arterial tissue content. Of the remaining 106, 19.6% were positive. The length of the biopsy and the number of arterial cross-sections were not significantly associated with its result. A positive biopsy was seen more in patients with low albumin (p = 0.010) and hypothyroidism (p = 0.017) but less in those with prior glucocorticoids treatment (p = 0.028). Predictors of a positive biopsy included male gender [OR 4.029, 95% CI (1.330-12.209), p = 0.014]; elevated ESR [OR 3.998, 95% CI (1.908-6.787), p = 0.023]; polymyalgia rheumatica (PMR) symptoms [OR 5.121, 95% CI (2.094-9.872), p = 0.001]; and advancing in age (6.5% per every additional year), [OR 1.065, 95% CI (1.005-1.130), p = 0.033]. 53.7% of the patients were eventually diagnosed with GCA; 39.2% of them were based on positive biopsy. In conclusion, old age, male gender, elevated ESR, and PMR symptoms increase the odds of positive TAB. Technical factors, such as biopsy length and the number of cross-sections, did not influence eventual biopsy results, highlighting the pivotal role of the clinical presentation of the patients in selecting patients for TAB.

Delayed Intravitreal Anti-VEGF Therapy for Patients During the COVID-19 Lockdown: An Ethical Endeavor.

PURPOSE: To assess the impact of Jordanian's Corona Virus Disease (COVID-19) lockdown on visual acuity and macular thickness in patients with macular edema receiving intravitreal injections, and to assess the ethical endeavor of lockdown among serious sight threatening conditions. PATIENTS AND METHODS: This retrospective observational study included patients planned for intravitreal injections who did not complete the planned course before the lockdown (ie, before 20th of March 2020). Data included demographics, indication for the intravitreal injection, corrected distance visual acuity (CDVA), and central macular thickness on Optical Coherence Tomography (OCT) before and after the lockdown. RESULTS: One-hundred and sixty-six eyes of 125 patients were studied, 68 (54.4%) patients were males, and the mean (± standard deviation, SD) age was 64.79 (±9.41) years. Mean (±SD) duration of delay in the planned injection was 60.97 (±24.35) days. The change in visual acuity was statistically significant for patients with diabetic macular edema (p= 0.045 improvement), patients with central retinal vein thrombosis (CRVO) (p= 0.05 deterioration), and patients with age-related macular degeneration (AMD) (p= 0.005 deterioration). Of interest, delay of more than 2 months and the previous need for 3 or more injections were significant poor prognostic factors for visual outcome for patients with diabetic macular edema (p=0.027 and 0.045). CONCLUSION: The impact of delay in the scheduled intravitreal injections resulted in variable outcomes depending on the indication. Triaging the urgency of patients should be based on the indication to support the equity principle of bioethics, where those in need are prioritized against others, depending on potential adverse outcome.

Characteristics, fates and complications of long-term silicone oil tamponade after pars plana vitrectomy.

BACKGROUND: Silicone oil tamponade has become a mainstay in treatment of advanced retinal detachment due to multiple etiologies. The aim of this study is to assess the characteristics, fates and complications of long-term silicone oil tamponade after par plana vitrectomy (PPV), and to compare the outcomes of different silicone oil viscosities used in a cohort of consecutive patients. METHODS: This is a retrospective comparative case series of eyes undergoing vitrectomy with silicone oil tamponade for retinal detachment by a single surgeon using different oil viscosities that were followed for one year with the silicone oil in situ. Visual acuity (VA), intraocular pressure (IOP) and complications associated with the follow up period were analyzed and compared. RESULTS: Eighty-five eyes of 85 patients were included in this study. Forty three patients had 1000 centistoke (cs) oil injected and 42 patients had 5000cs oil utilized. Demographic, cause of retinal detachment and preoperative ocular characteristics were similar in both groups. Long term complications in both groups included ocular hypertension (67.4% vs 66.7%), keratopathy due to silicone oil emulsification and migration to the anterior chamber (7.0% vs 11.9%), recurrent retinal detachment (4.7% vs 19%) and epiretinal membrane formation (7% vs 19%). In the 1000cs oil group, there was no significant difference between baseline IOP and any subsequent visit. There was a significant difference between baseline IOP and visits at day 1 (with IOP difference of 2.61 mmHg (±6.5)) (p = 0.028), 1 month (with IOP difference of 3.52 mmHg (±8.1)) (p = 0.026), 4 months (with IOP difference of 6.38 mmHg (±9.3)) (p = 0.005), and one year (with IOP difference of 4.24 mmHg (±11.1)) (p = 0.048), all higher in the post-operative period in the 5000cs oil group. Excluding the first post-operative day, no significant difference was found for VA between baseline visits and subsequent visits for either silicone oil groups. CONCLUSION: In this cohort of patients with long-term silicone oil tamponade after PPV to treat retinal detachment, IOP increased significantly in patients who received 5000cs silicone oil. There was no significant difference between other complication rates in patients receiving either oil viscosities. Long term silicone oil tamponade remains a viable option in certain cases, and a vigilant follow up for complications is necessary to limit any adverse effects and improve visual and surgical outcomes.

Platelet lysate promotes re-epithelialization of persistent epithelial defects: a pilot study.

PURPOSE: To study the use of autologous platelet lysate prepared in a standardized method for the healing of persistent corneal epithelial defects (PED). STUDY DESIGN: Clinical and experimental investigation. METHODS: In this prospective pilot study (ClinicalTrials.gov identifier NCT02979912), ten patients with a PED duration of a minimum 14 days were included. Autologous platelet lysate was prepared in a standardized methodology. Repeated freeze-thaw cycles were used to lyse the platelets. Patients were advised to apply the eye drops four times a day and were evaluated at baseline and on days 7, 14, 21, 28. RESULTS: No adverse events were reported due to the use of undiluted autologous platelet lysate. A total of 70% of patients had complete re-epithelialization within 28 days. Of these, 40% healed within 14 days (effective group) and 30% within 28 days (partially effective group). CONCLUSIONS: Undiluted autologous platelet lysate, prepared according to a standardized methodology, is a safe and effective adjunct therapy for the treatment of PED.

Characteristics, management, and outcome of squamous carcinoma of the conjunctiva in a single tertiary cancer center in Jordan.

AIM: To evaluate the features and outcome of management of malignant conjunctival squamous tumors in King Hussein Cancer Center (a referral tertiary cancer center in the Middle East). METHODS: Retrospective case series of 31 eyes for 31 patients with conjunctival squamous neoplasia. Main outcome measures included: age, gender, laterality, tumor location, pathological features, tumor stage, treatment modality, and outcome. RESULTS: Twenty (65%) patients were males and median age was 58y. Twenty-two (71%) eyes had the tumor in the nasal quadrant. Tumor invasion to nearby structures was seen in 19 (61%) eyes, including the cornea, fornix, eyelid, and orbit in 17 (55%), 1 (3%), 2 (6%), and 3 (10%) eyes, respectively. Eye salvage was achieved by surgical excision with cryotherapy followed by topical chemotherapy in 28 (90%) eyes, and orbital exenteration was necessary in 3 (10%) eyes due to orbital tumor invasion. Tumor recurrence was seen in 7 (23%) eyes, and the significant predictive factors for recurrence were tumor extension onto the nearby structures (P=0.04), tumor invasiveness (P=0.038), and tumor TNM stage (P=0.031). No significant change in visual acuity was seen, and disease related mortality was 6% (2 patients, both had orbital invasion by invasive squamous carcinoma). CONCLUSION: Conjunctival squamous carcinoma is more common in males. Advanced American Joint Committee on Cancer (AJCC) T-stage, tumor local invasion, more pathologically aggressive tumors, and surgical treatment alone (without adjuvant therapy) are associated with higher risk for recurrence, and orbital invasion is the most important poor prognostic factor for metastasis and death. Treatment strategies should be affected by tumor characteristics at presentation.

Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy.

AIMS: This open-label prospective phase I/IIa clinical study used autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) followed by mesenchymal stromal cells conditioned media (MSC-CM) for the first time to treat multiple sclerosis (MS) patients. The primary goal was to assess the safety and feasibility and the secondary was efficacy. The correlation between the MSC-CM content and treatment outcome was investigated. METHODS: Ten MS patients who failed conventional therapy were enrolled. Adverse events were recorded to assess safety. The Expanded Disability Status Scale (EDSS) was the primary efficacy measurement, the secondary included clinical (25WFT, 9-PHT), cognitive (MMS), ophthalmology (OCT, VEP), and radiological (MRI lesion and volume) tests. The MSCs-CM concentration of 27 inflammatory biomarkers was investigated. RESULTS: The treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL-6, IL-8, and VEGF MSC-CM content. CONCLUSION: The used protocol was safe and feasible with possible efficacy. The addition of MSC-CM could be related to the magnitude of EDSS improvement observed.

Canalicular pyocele: A new entity and literature review.

Canaliculoceles are rare, and under-recognized lesions of the upper lacrimal drainage system that may present as medial canthal masses or swelling. The current case is that of an 85-year-old female patient presented with a painful right upper lid medial, cystic swelling of 10-day duration involving the punctum and the upper canaliculus. A literature review showed that this is the seventh reported case of a canaliculocele but the first case of acute onset that is associated with inflammatory signs and symptoms and accumulation of purulent material. The term canalicular pyocele is suggested to describe this condition.

Keratoconus Asymmetry between Both Eyes Based on Corneal Tomography.

PURPOSE: To characterize the asymmetry between both eyes in patients with keratoconus based on corneal tomography. MATERIALS AND METHODS: All patients with keratoconus who presented to the eye clinic at Jordan University Hospital between January 2008 and November 2011 were included in the study. Using computerized corneal tomography, the keratometric values and indices of both eyes of participants with keratoconus and normal controls were compared. For both eyes to be considered symmetrical, the difference between the mean curvature power (Km), flat curvature power (K1), or steep curvature power (K2) in both eyes was equal to or <2.5 diopters, and the difference between the thinnest corneal points was equal to or <25.0 µm between both eyes. RESULTS: Ninety-eight patients with keratoconus and 49 normal participants were evaluated. The mean age of the participants was 26.3 ± 6.6 years. The results showed two populations of patients with keratoconus: one with asymmetrical corneas who were more affected by the disease and another with symmetrical corneas. As the disease severity increased, the differences between the two eyes increased for patients with the asymmetrical form, while both corneas of patients with the symmetrical form were similar. CONCLUSIONS: Corneal tomography identified two forms of keratoconus: symmetrical and asymmetrical. The latter tended to be more severe and occurred in a younger age group. Questions remain about whether the two keratoconic forms are specific to the Middle Eastern population and whether there are ethnic or demographic forms of the disease.

Isolated Bilateral Lacrimal Gland Agenesis.

A 5-year-old boy presented to the ophthalmology department complaining of absent tearing while crying. Slit-lamp examination showed decreased tear margin film with normal punctae. Orbit magnetic resonance imaging was done and showed bilateral absent lacrimal glands. This is the third case of isolated bilateral lacrimal gland agenesis in the literature. [J Pediatr Ophthalmol Strabismus. 2016;53:e35-e38.].

Outcomes of Penetrating Keratoplasty With Imported Corneas Compared With Local Corneas.

PURPOSE: The outcomes of penetrating keratoplasty (PK) were compared using local corneas obtained at the same hospital in which they were transplanted with corneas obtained from the United States and grafted at the Jordan University Hospital. METHODS: A retrospective, nonrandomized review included the medical records of 484 patients who underwent PK at the Jordan University Hospital from 2007 to 2009. Patients with at least 18 months of follow-up included 71 patients in the local group and 75 patients who received imported corneas. Data regarding the preoperative vision and diagnosis, tissue characteristics, preservation-to-surgery time of donor tissue on graft survival, and postoperative outcomes were collected. RESULTS: One hundred forty-six patients (mean age, 31.8 yrs ± 18.3 SD; range, 13-80 yrs) were included. Ninety-three (63.7%) patients were men. The most common indications for PK were keratoconus (67.8%) and corneal opacity (11%). Both groups were similar in age, indications, and outcomes. The success rates for PK after 18 months were 86% and 88% in the local and imported cornea groups, respectively; the difference between them did not reach significance (P = 0.196). The only significant (P < 0.001) factor was a longer preservation-to-surgery time in the imported group (8.6 ± 2.9 d) compared with the local group (4.5 ± 2.2 d). CONCLUSIONS: The success rate for PK remains relatively high (average, 87%) with both local and imported corneas. Despite the longer preservation-to-surgery time and older donor age for the imported corneas, no significant difference in graft outcomes was seen between the 2 groups.

Enucleation and evisceration at a tertiary care hospital in a developing country.

BACKGROUND: To analyze the demographics, indications, and surgical outcomes of anophthalmic surgery (enucleation and evisceration) at Jordan University Hospital during a 5-year period. METHODS: We conducted a retrospective chart review of patients who had undergone evisceration or enucleation between August 2006 and June 2011. The data collected included age at time of surgery, sex, affected eye, surgical indication, implant size, and postoperative complications. RESULTS: Anophthalmic surgery was performed for 68 eyes of 67 patients during the study period (42 (62 %) eviscerations and 26 (38 %) enucleations). Forty-three patients (64 %) were men, and 40 (59 %) eyes were right eyes. Trauma was the leading cause for anophthalmic surgery in 40 % of cases followed by a blind painful eye secondary to glaucoma (19 %) in the enucleation group and endophthalmitis (28.6 %) in the evisceration group. The most common anophthalmic surgery complication was wound dehiscence in 11.5 % of patients in the enucleation and 9.5 % in the evisceration groups. The mean and median sizes of the implants for evisceration were 16.6 and 18.0 mm, respectively; for enucleation, both were 20 mm. CONCLUSIONS: Evisceration was the preferred anophthalmic surgery in our series unless contraindicated. Trauma was the most common predisposing factor for evisceration and enucleation in our tertiary care center followed by blind painful eyes and endophthalmitis. The most common complication was wound dehiscence in both groups.

Intracranial Hypertension in Children: Etiologies, Clinical Features, and Outcome.

This retrospective study aimed to describe the clinical presentations, possible causes, and outcomes of children with idiopathic intracranial hypertension who presented to the authors' clinic. The mean age at onset of symptoms in the authors' cohort of 19 children was 6 years (range: 7 months to 12 years). Most patients (90%) were under 11 years old and (84.2%) symptomatic. The probable cause was identified in 7/19 (37.0%) patients. The most common cause was vitamin D deficiency (26.3%). Other associated probably coincidental comorbidities included sinusitis (5/19, 26.3%), hypophosphatasia (1/19), Pyle disease (1/19), and measles vaccine (1/19). Apart from 2 patients who required lumboperitoneal shunt, the cerebrospinal fluid pressure returned to normal in all patients within a period of 6 weeks to 1 year (average, 5 months). Of those who followed up with the authors' ophthalmologist, 30.7% developed optic atrophy or pallor; 75% of these patients had previous ocular comorbidities.

Prevalence of thrombophilic genetic factors among patients with retinitis pigmentosa.

PURPOSE: To determine the prevalence of thrombophilic factors in patients with retinitis pigmentosa (RP). METHODS: Fifty consecutive patients with RP and 50 controls matched by age and gender were tested for the presence of the following mutations: factor II (GA20210), factor V Leiden (GA1691), methylenetetrahydrofolate reductase (CT677), factor XIIIa (Val→Leu), ß-fibrinogen (GA455), tumor necrosis factor receptor (TNFRII) (M196R), plasminogen activator inhibitor-1 (PAI-1) (4 G/5 G), and plasminogen activator inhibitor-1 (PAI-1) (GA844). RESULTS: The following heterozygous mutations were found in patients/controls: factor V Leiden (12/14), factor XIIIa (20/30), methylenetetrahydrofolate reductase 677 TT (48/52), ß-fibrinogen GA455 (36/36), TNFRII (M196R) (40/42), PAI-1 4 G/5 G (40/48), and PAI-1 GA844 (50/52). The difference between patients with RP and the control group was not statistically significant for the prevalence of any of the studied factors (P > 0.05). CONCLUSION: In this study, thrombophilic mutations were not increased in patients with RP. Thrombophilic mutations do not seem to be risk factors for RP. Routine investigation of hereditary thrombophilia in these patients is not justified.

Long-term efficacy and safety of botulinum toxin A injections to treat blepharospasm and hemifacial spasm.

BACKGROUND: To evaluate efficacy and safety of botulinum toxin A injections after more than 10 consecutive years of treatment for benign essential blepharospasm and hemifacial spasm. DESIGN: Retrospective chart review at university-affiliated hospital. PARTICIPANTS: Study consisted of 64 patients treated with botulinum toxin A injections between October 2005 and May 2006. METHODS: Inclusion criteria included patients treated with at least one annual botulinum toxin-A injection for more than 10 consecutive years. Data collected included diagnoses and patient characteristics, injection dates, doses administered at each visit, response scores, duration of effect, and adverse events. MAIN OUTCOME MEASURES: Included changes in doses, response scores, duration of effects, and adverse events between the first and last botulinum toxin A injections. RESULTS: Thirty-two of 64 patients (mean age at first injection, 57.2 ± 12.4 years; 25 women) met the inclusion criteria. The mean duration of follow up was 14.1 ± 3.1 years (range 10-20 years; mean total visits 44.4 ± 19). A higher mean injection dose per visit was administered during the last year compared with the first year (26.8 ± 10.3 vs. 22.5 ± 7.5 units, respectively) (P = 0.003). The mean durations of effect during the first and last years were 12.4 ± 7.1 and 14.6 ± 7.0 weeks, respectively (P = 0.076). There were no significant differences between genders or between benign essential blepharospasm and hemifacial spasm subgroups. The most common adverse events were ptosis, lagophthalmos and dry eye. CONCLUSIONS: Botulinum toxin A is an effective, safe, long-term treatment for patients with benign essential blepharospasm and hemifacial spasm. Sustained treatment efficacy required higher doses; however, fewer adverse reactions developed.

Bilateral simultaneous pyogenic granuloma after perforated punctal plug insertion.

A 44-year-old woman with recurrent attacks of bilateral adenoviral keratoconjunctivitis infections presented with excessive tearing of 5 months' duration. Slit-lamp examination showed bilateral punctal stenosis. Tearing improved for 2 months after insertion of perforated silicone punctal plugs, after which she had a bilateral foreign-body sensation due to pyogenic granuloma pushing through the lumen of the silicone plugs. The foreign-body sensation improved after removing the plugs and a short course of topical steroid-antibiotic eye drops.

Ocular manifestations of Behçet's disease in Jordanian patients.

PURPOSE: To study the prevalence, manifestations and severity of ocular involvement of Behçet's disease in Jordanian patients. METHODS: The study population consisted of 43 patients diagnosed to have Behçet's disease through Rheumatologist's examinations conducted at Jordan University Hospital between January 2002 and July 2009. The sample involved patients who displayed ocular manifestations. This included 18 patients; 12 males and 6 females with a mean age of 35 years (SD = 17.26). Ophthalmological examinations and retrospective analysis of medical files were carried on. RESULTS: Ocular manifestations were seen in 41.9% of patients. The most common manifestation for Behçet's disease was vitritis with a prevalence of 55.6%, followed by anterior uveitis and retinal vasculitis (50% for each). On the other hand, the most frequent complications involved were cataract, cystoid macular edema (CMO), posterior synechiae and glaucoma with a prevalence of (44.4%), (33.3%), (11.1%) and (5.6%), respectively. CONCLUSION: The prevalence and severity of ocular lesions in Behçet's disease is relatively low in Jordanian patients. This result indicates that early diagnoses and intervention might delay or even prevent vision loss for those patients.