Search

Catherine Wang,1 Katherine A Joltikov,1,2 Sasha Kravets,2,3 Deepak P Edward2,4 1University of Illinois at Chicago College of Medicine, Chicago, IL, USA; 2Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA; 3Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA; 4Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Deepak P Edward, Illinois Eye and Ear Infirmary, 1009 S Wood St, Chicago, IL, 60612, USA, Tel +1 312 996 6590, Fax +1 312 996 4255, Email deepedwa@uic.eduPurpose: The purpose of this study was to evaluate Computer Vision Syndrome (CVS) in undergraduate and medical students since transitioning to online learning during the COVID-19 pandemic.Patients and Methods: This was a cross-sectional single center survey-based study using a validated CVS questionnaire (CVS-Q). The survey was distributed to 20,080 undergraduate students and 680 medical students at the University of Illinois at Chicago. The primary outcome measures were prevalence of CVS (based on CVS severity score of 6 or more), frequency of CVS and intensity of CVS symptoms.Results: The survey was completed by 2300 undergraduate students (11.4% response rate) and 154 medical students (22.6% response rate). The prevalence of CVS was 77.1% in undergraduate students and 69.1% in medical students. CVS-Q severity scores were highest for headaches and eye dryness, with over half of students reporting worsening of symptoms since March 2020. Increased time spent on online learning (undergraduate: P < 0.001, medical: P = 0.018), blue light glasses usage (undergraduate: P < 0.001, medical: P = 0.0015), and increased number of device usage were associated with higher CVS severity scores (undergraduate: P < 0.001, medical: P = 0.0032).Conclusion: CVS among undergraduate and medical students has increased since the start of the COVID-19 pandemic. More focus should be placed on the management of CVS for students in higher education. Physicians should be cognizant of the consequences of online learning and be proactive about providing advice regarding preventative measures.Keywords: digital eye strain, screen time

Ahmad AlJaloud,1,2 Sara AlHilali,1 Deepak P Edward,1,3 Khabir Ahmad,4 Rizwan Malik1,5 1Glaucoma Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 2King Abdullah bin AbdulAziz University Hospital, Riyadh, Saudi Arabia; 3University of Illinois Eye and Ear Infirmary Chicago, Chicago, IL, USA; 4Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 5Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, CanadaCorrespondence: Khabir Ahmad, Research Department, King Khaled Eye Specialist Hospital, Al Aruba Branch Road, Riyadh, 12329, Saudi Arabia, Tel +966 11 482 1308, Email drkhabir@gmail.comPurpose: We describe the technique of trimming the 350 mm2 AADI glaucoma shunt plate and report preliminary results that test the hypothesis that the IOP-lowering efficacy of the trimmed AADI glaucoma shunt is comparable to the Baerveldt 250 mm2 glaucoma drainage implant with a comparable safety profile to the standard AADI implant.Methods: Consecutive patients who had received the modified trimmed-plate AADI, standard AADI and Baerveldt 250 mm2 were included in the study. This included patients with refractory or primary or secondary glaucoma of all ages and eyes with and without previous glaucoma surgery. The decision for trimming the AADI plate was made according to the surgeon’s perceived risk of hypotony. Pre-operative, intraoperative and post-operative data were collected from the hospital electronic medical record system. Surgical success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg on two consecutive visits after 3 months, whilst maintaining at least LP vision and avoiding re-operation for glaucoma.Results: The sample consisted of 69 eyes (19 with trimmed-plate AADI implant; 36 eyes with the standard AADI implant and 14 eyes who received a BGI-250). The mean IOP reduction at 1 year was 15 mmHg for the Baerveldt-250, 10 mmHg for the AADI and 13 mmHg for the trimmed-plate AADI. The surgical success rate of the implants over 1 year was 85.7% (95% CI, 53.9– 96.2%) for BGI-250, 81.5% (62.6– 91.5%) for standard AADI and 78.2% (51.7– 91.3%) for the trimmed AADI.Conclusion: Trimming the plate of the AADI manually may provide a safe and low-cost method of obtaining a successful surgical outcome in eyes at high risk of hypotony.Keywords: refractory glaucoma, non-valved glaucoma drainage device, AADI, trimmed-plate implant, hypotony

Ahmed Al Habash,1,2 Leyla Ali Aljasim,1 Ohoud Owaidhah,1 Deepak P Edward1,3 1King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia; 2Department of Ophthalmology, University of Dammam, Dammam, Saudi Arabia; 3Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: The success of trabeculectomy, which is considered the gold standard in the surgical treatment of glaucoma, depends on the wound healing response. The introduction of antiproliferative agents such as mitomycin C (MMC) has increased the success rates of trabeculectomy. However, complications due to these agents can be challenging to manage. Hence, it is important to determine the most efficacious dose and duration of exposure. Multiple studies suggest that many factors, including but not limited to MMC preparation, different concentrations, different exposure times, and method of application may affect success rate, and these factors were reviewed in this article. We concluded that lower concentrations of MMC that are prepared and applied in a standardized fashion, such as that using the Mitosol® kit (for 2–3 minutes) during trabeculectomy, could potentially provide trabeculectomy success rates similar to that reported with off-label preparations, and that such a treatment regime could result in in lower complication rates than higher doses of MMC. Keywords: mitomycin C, Mitosol, filtering surgery, trabeculectomy, outcomes

Shameema Sikder,1 Jia Luo,2 P Pat Banerjee,2 Cristian Luciano,2 Patrick Kania,2 Jonathan C Song,1 Eman S Kahtani,3 Deepak P Edward,1,3 Abdul-Elah Al Towerki3 1Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA; 2College of Engineering, University of Illinois at Chicago, Chicago, IL, USA; 3King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia Purpose: To evaluate a haptic-based simulator, MicroVisTouch™, as an assessment tool for capsulorhexis performance in cataract surgery. The study is a prospective, unmasked, nonrandomized dual academic institution study conducted at the Wilmer Eye Institute at Johns Hopkins Medical Center (Baltimore, MD, USA) and King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia).Methods: This prospective study evaluated capsulorhexis simulator performance in 78 ophthalmology residents in the US and Saudi Arabia in the first round of testing and 40 residents in a second round for follow-up.Results: Four variables (circularity, accuracy, fluency, and overall) were tested by the simulator and graded on a 0–100 scale. Circularity (42%), accuracy (55%), and fluency (3%) were compiled to give an overall score. Capsulorhexis performance was retested in the original cohort 6 months after baseline assessment. Average scores in all measured metrics demonstrated statistically significant improvement (except for circularity, which trended toward improvement) after baseline assessment. A reduction in standard deviation and improvement in process capability indices over the 6-month period was also observed.Conclusion: An interval objective improvement in capsulorhexis skill on a haptic-enabled cataract surgery simulator was associated with intervening operating room experience. Further work investigating the role of formalized simulator training programs requiring independent simulator use must be studied to determine its usefulness as an evaluation tool. Keywords: medical education, computer simulation, educational assessment, technology assessment, cataract surgery

Ramzi Al Judaibi,1 Khaled K Abu-Amero,2,3 Jose Morales,1 Sami Al Shahwan,1 Deepak P Edward1,4 1King Khaled Eye Specialist Hospital, 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, USA; 4Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore MD, USA Purpose: Here, we present two patients with congenital anterior staphyloma, with mutations in the CYP1B1 gene. Methods: We reviewed the medical records, including the genetic analysis. Results: Two unrelated patients presented with congenital anterior staphylomas. Both patients showed mutations in the CYP1B1 gene. The first patient, the product of a consanguineous marriage, showed a homozygous misssense mutation g.3987G>A (p.G61E). The second patient had compound heterozygous misssense mutations [g.4160 G>T (p.A119S) and g.8131 C>G (p.L432V)]. Conclusion: CYP1B1 gene mutation may be associated with congenital anterior staphylomas. Keywords: mutation analysis, congenital glaucoma, consanguinity, congenital aphakia

The purpose of this study was to determine the relationship between clinical measures of visual function and driving-related skills in patients with glaucoma who had good visual acuity in at least one eye and mild to moderate visual field loss. Methods. Twenty-five patients with glaucoma and twenty-nine age-equivalent normally sighted control subjects were included in the study. We tested each patient on an interactive driving simulator and collected vision data, including Lighthouse visual acuity, Goldmann and Humphrey visual fields, and Pelli-Robson contrast sensitivity. Information about real-world accident history for the previous 5-year period was obtained. Results. The glaucoma patients did not have significantly more simulator or real-world accidents than the normally sighted group. There were no significant differences between the groups in performance on seven of the eight simulator indexes that were measured. Of the clinical visual function measures, only lower contrast sensitivity in the eye with better contrast sensitivity correlated with driving skills, including slower speeds (r(24) = 0.58, p

Background: Fanconi's syndrome (FS) is characterized by type-2 renal tubular acidosis, short stature, and renal rickets, along with glycosuria, aminoaciduria, hypophosphaturia, and urinary bicarbonate wasting. The genetic form of FS has been linked to HNF4A variants. Although additional clinical features such as hearing impairment have recently been associated with HNF4A-linked FS, its ocular manifestation has not been described., Material and Methods: Presenting a case of a 5-year-old male child with bilateral progressive corneal opacification and the presence of bilateral greyish-white deposits in the interpalpebral region since infancy. A next-generation sequencing (NGS)-based genetic testing was performed for the child followed by parental genetic testing for the identified variant. Furthermore, relevant works of literature were reviewed related to this condition., Results: Detailed corneal findings showed a bilateral band-shaped keratopathy (BSK) in the patient. Physical and systemic findings showed signs consistent with FS. Sequencing analysis revealed a novel heterozygous c.635C>T, (p.Pro212Leu) variant in the HNF4A gene in the proband and mother, while the father had a normal genotype., Conclusions: Our case highlights the occurrence of BSK in an exceptionally rare manifestation of hereditary FS linked to HNF4A gene variant. The variant exists both in proband and asymptomatic mother. Therefore, the variable penetrance which is known to exist in HNF4A is acknowledged in this context. This report suggests the first documented instance establishing a plausible connection between BSK and HNF4A-associated FS, characterized by the variable penetrance attributed to the HNF4A gene.

Purpose: The aim of this study was to report the clinical profile and patterns of recurrence after femtosecond laser-assisted anterior lamellar keratoplasty (FALK) in Reis-Bucklers corneal dystrophy., Methods: This is a case series of 5 eyes of 4 patients with Reis-Bucklers corneal dystrophy. Clinical images of recurrence were correlated with the high-resolution optical coherence tomography. Histopathologic examination of excised corneal samples was performed when possible., Results: The median time to recurrence was 2 (1-5) years after FALK. Of the 5 eyes, 1 eye had primary FALK, whereas 4 eyes had secondary interventions, which included previous phototherapeutic keratectomy (once in 1 eye and twice in 2 eyes), and previous penetrating keratoplasty, followed by phototherapeutic keratectomy (1 eye). Recurrence was noted at the level of the subepithelium. In addition, 1 eye showed interface deposits along with epithelial downgrowth at the graft-host bed., Conclusions: The 2 distinct patterns of recurrence noted were at the subepithelial region and the interface. The clinical patterns of recurrence favor an epithelial origin of recurrent deposits., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications., Methods: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications., Results: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate ( p  = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant., Conclusions: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Congenital hereditary endothelial dystrophy (CHED) is a rare genetic corneal disorder causing progressive cornea clouding and significant visual impairment. CHED remains a leading indication for pediatric corneal transplantation despite its infrequency, particularly in regions with high consanguinity rates like Southeast Asia. Identifying the Solute Carrier Family 4 Member 11 (SLC4A11) gene as the genetic basis of CHED has led to the discovery of it's various genetic variations. However, a comprehensive understanding of its clinical-genetic correlation, pathophysiology, and optimal management is ongoing. This review aims to consolidate current knowledge about CHED, covering its genetic origins, pathophysiological mechanisms, clinical presentation, and management strategies. Surgical intervention, such as penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK), remains the primary treatment. DSAEK and DMEK offer advantages over PK, including quicker visual recovery, reduced complications, and longer graft survival, especially in the pediatric age group. The timing of surgical interventions depends on disease severity, age at presentation, comorbidities, and visual potential. Elevated oxidative stress in CHED corneal tissue suggests potential benefits from anti-inflammatory drugs to rescue mutated endothelial cells. Considering the limitations of corneal graft surgeries, exploring novel gene-based molecular therapies are essential for future management. Early diagnosis, appropriate surgical interventions, amblyopia control, and genetic counseling for predictive analysis are pivotal for optimizing CHED management. A multidisciplinary approach involving ophthalmologists, researchers, and genetic counselors is essential for precise diagnosis and optimal care for CHED patients., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2023 Taiwan J Ophthalmol.)

Axenfeld-Rieger syndrome (ARS) is a rare autosomal-dominant neurocristopathy that presents with a variety of classical ocular and systemic findings. The pathophysiology of the disease involves anterior segment dysgenesis, and patients may present with ophthalmic complications early in life, including secondary glaucoma, high refractive errors, amblyopia, and permanent visual damage. There are a limited number of studies in the literature that focus primarily on pediatric patients with ARS. The purpose of this article was to review the current literature on clinical presentation, genetic associations, diagnosis, secondary complications, and treatment of ARS in pediatric patients. Evaluating the essential clinical aspects of the disease in children may allow for earlier diagnosis and treatment and prevent visual morbidity from amblyopia and secondary glaucoma that may result in permanent visual damage., Competing Interests: The authors declare that there are no conflicts of interests in this article., (Copyright: © 2023 Taiwan J Ophthalmol.)

Purpose: The purpose of this study was to identify the genetic cause of aggressive corneal vascularization in otherwise healthy children in one family. Further, to study molecular consequences associated with the identified variant and implications for possible treatment., Methods: Exome sequencing was performed in affected individuals. HeLa cells were transduced with the identified c.1643C>A, p.(Ser548Tyr) variant in the platelet-derived growth factor receptor beta gene (PDGFRB) or wild-type PDGFRB. ELISA and immunoblot analysis were used to detect the phosphorylation levels of PDGFRβ and downstream signaling proteins in untreated and ligand-stimulated cells. Sensitivity to various receptor tyrosine kinase inhibitors (TKIs) was determined., Results: A novel c.1643C>A, p.(Ser548Tyr) PDGFRB variant was found in affected family members. HeLa cells transduced with this variant did not have increased baseline levels of phosphorylated PDGFRβ. However, upon stimulation with ligand, excessive activation of PDGFRβ was observed compared to cells transduced with the wild-type variant. PDGFRβ with the p.(Ser548Tyr) amino acid substitution was successfully inhibited with tyrosine kinase inhibitors (axitinib, dasatinib, imatinib, and sunitinib) in vitro., Conclusions: A novel c.1643C>A, p.(Ser548Tyr) PDGFRB variant was found in family members with isolated corneal vascularization. Cells transduced with the newly identified variant showed increased phosphorylation of PDGFRβ upon ligand stimulation. This suggests that PDGF-PDGFRβ signaling in these patients leads to overactivation of PDGFRβ, which could lead to abnormal wound healing of the cornea. The examined TKIs prevented such overactivation, introducing the possibility for targeted treatment in these patients.

Purpose: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens., Methods: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls., Results: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048)., Conclusions: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease., Competing Interests: J.T.R. has in the past consulted for Genentech/Roche and was a co-investigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. J.T.R., R.A.D., and D.O.K. are consultants, while G.J.H. and B.S.K. have in the past consulted for Horizon Pharmaceuticals, which manufactures teprotumumab. Other authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: The purpose of this study was to compare the corneal endothelial characteristics in Axenfeld anomaly (AXA), Rieger anomaly (RGA), and Axenfeld-Rieger anomaly/syndrome with age-matched healthy controls., Methods: This is a retrospective, comparative case-control study of 52 eyes of 30 patients with AXA/RGA and AXA/S and 36 controls., Results: Median age at endothelial imaging was 21.5 years (interquartile range, 13.8-33.3 years). In the study group, the mean endothelial cell density (ECD) was 2112.4 ± 78.5 cells/mm 2 , the mean cell area (MCA) was 526.9 ± 28.5 μm 2 , and the coefficient of variation of cell size was 41.2 ± 1.8%. The ECD was significantly (all, P < 0.0001) lower than controls, while MCA ( P < 0.0001), SD of cell size ( P < 0.0001), and maximum cell area ( P = 0.0007) were significantly higher than controls. Four eyes of 3 patients had guttae on slitlamp evaluation and endothelial imaging. There were no differences in the corneal endothelial characteristics among the clinical subtypes., Conclusions: Patients with AXA, RGA, and Axenfeld-Rieger anomaly/syndrome have lower ECD and increased MCA compared with normal eyes. The reduced ECD associated with inherent anterior segment alterations can predispose to the risk of postcataract surgery endothelial decompensation in these eyes. The association of guttae in some eyes needs further investigational studies., Competing Interests: Conflicts of interest statement: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Topical netarsudil 0.02% may reduce intraocular pressure (IOP) by decreasing episcleral venous pressure (EVP), which carries theoretical utility for glaucoma associated with elevated EVP. A role for netarsudil in patients with elevated EVP is evaluated in a pilot investigation using a cohort of individuals with Sturge-Weber syndrome (SWS)., Methods: Retrospective study of patients with SWS and glaucoma who were treated with netarsudil. Five patients (six eyes) were identified. Data collected included demographics, visual acuity, IOP, glaucoma medical and surgical treatments, and adverse effects of netarsudil., Results: Mean age was 13.6  ±  8.5 years. EVP elevation was presumed based on clinical stigmata and/or historical features. Mean number of baseline glaucoma medications was 3.3  ±  1.2. There was a significant reduction in the IOP at netarsudil initiation (mean 26.2  ±  4.5 mmHg) to 1 month of netarsudil therapy (mean 20.2  ±  3.8 mmHg, p   =  0.0283 ) and latest IOP on netarsudil (mean 17.6  ±  1.4 mmHg, p   =  0.0034). Mean duration of netarsudil therapy was 18.7  ±  11.8 months. Three patients required additional glaucoma procedures; one patient required an additional glaucoma medication. Three eyes (50%) developed conjunctival hyperemia. One patient discontinued netarsudil at 29 months, to reduce drop burden., Conclusions: Netarsudil can effectively reduce IOP in patients with SWS, even when used as a fourth or fifth glaucoma medication. A possible role for netarsudil in the management of patients with elevated EVP is suggested pending further future investigations.

Purpose: To describe a professionalism survey tool and its use to assess knowledge of medical professionalism in ophthalmology training programs in Central India., Settings and Design: Multi-center survey study., Methods: A validated 33-question, scenario-based survey addressing professionalism attributes was administered at five centers in central India. The attributes tested included "personal characteristics," "physician-patient relationships," "workplace practice and relationships," and "socially responsible behaviors." A mean attribute score (%) was calculated and compared to "gold standard" responses by a group of expert senior ophthalmologists (100% agreement for responses)., Results: A total of 225 participants completed the survey; 124 residents, 47 fellows, and 54 consultants (98.4% response rate). The total mean attribute score was 80.7 ± 9.1 (min 16.67, max 100). There was variation in the mean attribute score by professionalism attribute (P < 0.001), and a trend toward higher mean attribute scores for consultants compared to trainees across all attribute groups. The scores for "personal characteristics" (93 ± 9.7) and "physician-patient relationship" (82 ± 15.8) were the highest, whereas scores for "socially responsible behaviors" (73.9 ± 18.6) and "workplace practices" were low (72 ± 13)., Conclusions: There is a generally high level of professionalism knowledge among ophthalmologists in central India. The results suggest that experience does impact knowledge of professionalism. Potential for improvement in professionalism exists in around "workplace practices", and around "socially responsible behaviors". These findings may serve as a valuable discussion starter and teaching tool to enhance professionalism in ophthalmology training programs., Competing Interests: None

Purpose: Our study aimed to evaluate the utility of the anterior segment morphometry for objectively assessing anterior segment architectural changes of corneal clouding in the mucopolysaccharidoses (MPS) cohort and to investigate whether these measurements correlate with the slit-lamp findings on the cornea and early diagnosis of glaucoma., Methods: This retrospective study involved 70 eyes of 35 children with cloudy cornea due to MPS variants. Anterior segment architectural alterations were measured using anterior segment imaging and biometry in MPS children and compared with controls., Results: Mean age of the cohort at the time of assessment was 7.9 ± 4.5 years. Males constituted two-thirds of the cohort. Variants of MPS with cloudy cornea were as follows: Type I (62%), Type IV (11%), and Type VI (22%). Morphometric measurements were available in 22 eyes of 11 MPS children and an age-matched healthy control group. There were significant differences between MPS cohort and controls in refraction in Diopters (5.03 ± 0.39 and 0.01 ± 0.04; P < 0.0001), axial length (AXL) in mm (21.39 ± 0.28 and 23.04 ± 0.28; P = 0.0002), average keratometry in Diopters (40.67 ± 0.44 and 42.83 ± 0.44; P < 0.0001), anterior chamber depth (ACD) in mm (2.92 ± 0.07 and 3.65 ± 0.07; P < 0.0001), and intraocular pressure (IOP) in mmHg (25.2 ± 2.0 and 14.1 ± 2.3; P = 0.0003). Secondary glaucoma was observed in 28% of the MPS cohort., Conclusion: The anterior segment morphometry in the cloudy cornea due to MPS provides an objective measurement of anterior segment architectural changes, thus diagnosing early-onset secondary glaucoma. These findings highlight that cloudy cornea due to MPS variants merits close monitoring throughout life., Competing Interests: None

Purpose: This study describes the surgical outcomes of selective endothelialectomy in Peters anomaly (SEPA), a relatively new technique to manage Peters anomaly (PA)., Methods: This study included 34 eyes of 28 children who had a visually significant posterior corneal defect due to PA and underwent SEPA between 2012 and 2019. A selective endothelialectomy from the posterior corneal defect was performed while preserving Descemet membrane. The primary outcome measure was the resolution of corneal opacification. The secondary outcome measures were functional vision, complications, and risk factors for failure., Results: At a mean postoperative follow-up of 0.96 ± 0.20 years, 29 eyes (85.3%) maintained a successful outcome. Mean preoperative and postoperative best-corrected visual acuities were 2.55 ± 0.13 and 1.78 ± 0.13 ( P < 0.0001), respectively. Ambulatory functional visual improvement was seen in 97%, and 23% attained vision ranging between 20/190 and 20/50. Corneal opacification failed to clear in 5 eyes (15%). Risk factors associated with surgical failure were female sex ( P = 0.006), disease severity ( P < 0.0001), glaucoma ( P = 0.001), and additional interventions after SEPA ( P = 0.002). In multivariate analysis, only disease severity (ie, a type 2 PA) was a significant risk factor for the failure of SEPA. There were no sight-threatening complications., Conclusions: SEPA is a safe and effective technique in select cases of posterior corneal defect due to PA. SEPA could be a potential surgical alternative to pediatric keratoplasty or optical iridectomy in children with central corneal opacification smaller than 7 mm due to PA., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To examine barriers and adherence to topical glaucoma medication in a pediatric glaucoma population in Saudi Arabia., Methods: This cross-sectional study was undertaken at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia during 2016-2017. Parents (father or mother) of children aged 6 months to 15 years with a history of glaucoma were interviewed. Rasch analysis was performed to assess the psychometric properties of the developed 12-item barriers-to-adherence tool (BAT-12) and to identify barriers deemed highly important. The 12-items were adapted from previous studies examining different barriers to adherence in different populations. Medication adherence was assessed by asking parents a series of closed-ended questions about the frequency of missed medications. Determinants of missed medications on at least 1 out of the last 3 days were examined using Poisson regression., Results: One hundred and six parents were interviewed. The 12-item scale had acceptable psychometric properties. Barriers deemed important were forgetfulness (logit -0.59), complex dosing regimen (logit 0.09), and being too busy with other work/activities (logit 0.14). When asked how often, on average, their child missed the prescribed medication, 26 (24.5%) reported daily, 17(16.0%) reported few times per week, and 32 (30.2%) reported once per week. A third of parents (n = 37, 34.9%) reported having missed giving all drops on at least one day in the last 3 days. Poisson regression with robust variance revealed that increase in age of the child (prevalence ratio, 1.08 [95% CI, 1.03-1.14]; p = 0.003) and increase in parents' barriers score (prevalence ratio, 2.13 [95% CI, 1.49, 3.03]; p < 0.001) were significantly associated with having missed medications on at least one out of the last three days while adjusting for the effect of father's current employment status and area of residence., Conclusions: The tool we used to examine barriers to glaucoma medication had acceptable psychometric properties and could be used and strengthened in future studies. Our study highlights poor adherence to glaucoma medications among children with glaucoma.

Purpose: Programmed cell death protein 1 (PD-1) and DNA mismatch repair (MMR) deficiency play an important role in tumour progression and response to treatment.Both markers have been studied in some ocular tumours but little is known about these markers in orbital tumours. This pilot study reports on PD-L1 expression and MMR mutations using next generation sequencing (NGS) in specific orbital tumours., Methods: We reviewed surgical specimens from patients with rhabdomyosarcoma, adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and biopsy negative tissue from orbital tumours used as a control. immunohistochemistry (IHC) was performed on Formalin fixed paraffin embedded tissue using a PD-L1 antibody. DNA was extracted for targeted gene panel NGS of the MMR genes PMS2 , MLH1 , MSH6 and MSH2 ., Results: The study included 17 orbital specimens. Scattered membrane PD-L1 staining was noted in 3/6 rhabdomyosarcoma specimens without an accompanying lymphocytic infiltrate. PD-L1 immunostaining was absent in 3/3 ACC, and 5/6 PA specimens. PD-L1 immunostaining was not detected in 2/2 control specimens. 4/17 samples shared the same pathogenic mutation in the MLH1 gene, including 3/6 rhabdomyosarcoma and 1/3 ACC samples. 1/6 PA samples had a mutation in MSH6 ., Conclusions: Our study demonstrated scattered, non-quantifiable or absent PD-L1 staining in a limited sample of orbital tumours suggesting that PD-1/PD-L1 inhibitor therapy may not be useful in treatment of malignant orbital tumours (rhabdomyosarcoma and ACC) when refractory to conventional therapy. Our pilot study suggest that PD-L1/MMR axis might not play a major role in the pathogenesis of primary orbital tumour.

Purpose: Pigmented basal cell carcinomas (PBCC) is an uncommon variant of basal cell carcinoma of the periocular region with limited information in the literature. We highlight the clinicopathological profile and somatic mutations in periocular PBCC., Methods: The clinicopathological features and somatic mutations in patients with periocular PBCC were examined and compared with periocular non-PBCC reported in the literature. Next-generation sequencing panel analysis for the excised tumors identified somatic mutations., Results: In a total of 31 patients, PBCC was common in females (54%; p = 0.03); as a unilateral lower eyelid (n = 22; 71%), solitary mass (n = 30; 98%). Pathologic subtypes were variable. Most were nodular or mixed variants (n = 23; 74%). During the follow up (2.5-4.5 years), 1 patient (3.5%) had a recurrence. The clinical and pathologic features of PBCC were similar to those reported in nonperiocular locations. Somatic mutations detected in 25/31 tumors. Variants in 50/161 genes in the panel were noted. PTCH1 (14/31), TERT (12/31), and SMO (7/31) variants were common. Fifteen patients had novel drivers, including POLE, FANCD2, and CREBBP. SMO mutations were significantly more common in females (7/7), lower eyelid (5/7), and TERT mutations were more common in nodular subtype (10/12)., Conclusions: In this large cohort of a relatively uncommon variant of BCC, the clinicopathological features and tumor behavior of PBCC was similar to periocular non-PBCC. The somatic mutation spectrum of PBCC resembles that reported in nonperiocular cutaneous BCC with novel drivers identified. We identified several potential actionable mutations that could be targeted with molecular therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix., Design: Case series., Participants: Archived specimens from patients with PE., Methods: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE., Results: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma., Main Outcome Measures: Identify location of PE and its immunohistochemical features., Conclusions: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity., (Published by Elsevier Inc.)

Competing Interests: None

Background: Orbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy., Aims: To test the hypothesis that shared signalling pathways are activated in different forms of OID., Methods: In this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls., Results: Among the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways., Conclusions: Although OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways., Competing Interests: Competing interests: JTR has in the past consulted for Genentech/Roche and was a coinvestigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. JTR, RAD, BSK, DOK, and GJH are consultants to Horizon Pharmaceuticals which manufactures teprotumumab. JTR receives research support from Horizon Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited., Competing Interests: None

Purpose: To determine the incidence of cosmetic-related lacrimal sac black deposits (LSBDs) in primary-acquired nasolacrimal duct obstruction (PANDO) biopsies and the role of LSBD in the pathogenesis of PANDO, in addition to their association with dry eye disease (DED)., Methods: A clinicopathological study included all patients who underwent surgical management of PANDO. We excluded patients in whom lacrimal sac biopsy was not taken during the surgery. Lacrimal sac tissues were evaluated for the presence of LSBD and related inflammation, with correlation to the demographics, clinical presentation, and pre-operative clinical assessment of dry eye. P <0.05 was considered statistically significant., Results: Of the 177 PANDO specimens, black deposit aggregates were noted in the sac stroma of 61 lacrimal sac specimens (34.5%; 95% confidence interval: 27.5-47.5). LSBDs were significantly more common in females ( P < 0.001). The age, residence, past ailments, and laterality were not associated with LSBD. Dry eye was more common with LSBD ( P = 0.004). Other presenting symptoms were not significantly associated with LSBD. The stromal black deposits in biopsies were mostly extracellular or in macrophages. The LSBD in only 10 specimens demonstrated birefringence. Energy dispersive spectroscopy determined that carbon and sulfur were the main elements in the black aggregates., Conclusion: Cosmetic-related LSBD is unlikely to play a role in the pathogenesis of PANDO. However, they were significantly associated with DED., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Ophthalmology.)

Purpose: To determine the frequency and risk factors of narrow angles in pseudoexfoliation (PXF) patients., Methods: A prospective case-control study was conducted during the period from March 2017 to December 2020. Adult patients (above 40 years) presenting with PXF were consecutively enrolled (study group). Cases were matched with individuals above 40 years presenting to a comprehensive ophthalmology clinic without evidence of PXF (control group)., Results: We enrolled 196 PXF patients and 98 controls. The occurrence of narrow angles was 25% in the PXF group and 5.1% in the control group (P = 0.0001). Compared to controls, PXF patients were older (72.6 ± 9.6 vs. 64.4 ± 8.5, P < 0.0001) and had a lower mean ACD (2.79 ± 0.4 vs. 3.05 ± 0.4, P < 0.0001). There was no difference in AL measurements between both groups (23.3 ± 1.4 vs. 23.7 ± 1.0, P = 0.0714). After stratification by age group and gender, the risk of narrow angles was higher in PXF patients above 70 years (OR, 4.15; 95% CI, 0.91-23.87; P, 0.044). There was no gender difference in the risk of developing narrow angles., Conclusion: Narrow angles are more frequently encountered in PXF patients compared to controls. Advanced age (> 70 years) is significantly associated with an increased likelihood of developing narrow angles., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To describe the clinical spectrum and management of glaucoma in congenital aphakia., Methods: The demographics and clinical spectrum of eyes with congenital aphakia with and without glaucoma were compared, and management outcomes of congenital aphakia cases with glaucoma were studied retrospectively between April 2000 and June 2020., Results: There were a total of 168 eyes (84 subjects) with a diagnosis of congenital aphakia, of which 29 eyes of 18 subjects were diagnosed with glaucoma. Corneal opacity was the presenting complaint in 26/29 eyes with glaucoma and 139/139 eyes without glaucoma. The (interquartile range (IQR)) horizontal corneal diameterwas 10.5mm (IQR, 9.0-12.5) and 8mm (IQR, 5-10) in eyes with and without glaucoma (P = 0.01), respectively. The median (IQR) axial length was 17.5mm (IQR, 13.5-19.5) and 15mm (IQR, 14-16) mm in eyes with and without glaucoma (P = 0.03), respectively. Nineteen eyes with glaucoma had adequate intraocular pressure (IOP) control with one medication. Three eyes underwent transscleral diode cyclophotocoagulation and maintained IOP without medications. Three eyes underwent trabeculectomy and trabeculotomy, trabeculectomy followed by penetrating keratoplasty, and trabeculectomy, respectively, of which two eyes became phthisical. At the last follow-up, the median (IQR) IOP was 14 mm Hg (IQR, 14-17) Hg. The median(IQR) follow-up duration was 4.53 months (IQR, 2.03- 48.06)., Conclusion: One-fifth of the eyes with congenital aphakia had secondary developmental glaucoma. The corneal diameter and axial lengths were higher in the eyes with glaucoma compared to eyes without glaucoma. Medical management is the preferred short-term mode of IOP control. Transscleral cyclophotocoagulation may be preferred over surgical intervention., Competing Interests: None

Purpose: To determine the magnitude, determinants, and public health issues related to diabetic retinopathy (DR) in India using 2019 data from a for-profit telescreening program. Methods: Digital retinal images were captured using a nonmydriatic fundus camera and transferred via the telescreening program to a reading center. Ophthalmologists trained in DR image reading created the DR status reports. Age/sex-adjusted rates of DR, sight-threatening DR (STDR), and diabetic macular edema (DME) were calculated and correlated with known risk factors. Results: Images of 51,760 Indian diabetic patients (103,520 eyes) were reviewed. The prevalence of DR, STDR, and DME was 19.1% (95% confidence interval [CI]: 18.9-19.5), 5.1% (95% CI: 4.9-5.3), and 3.9% (95% CI: 3.7-4.1), respectively. Based on these data, we projected 14.7 million cases of DR, 3.9 million with STDR, and 3.0 million DME cases in India. Statistically significant risk factors for DR were male gender (odds ratio [OR] = 1.19, p < 0.001), older age (χ 2  = 270, df = 3, p < 0.001), history of cataract surgery (OR = 2.0, p < 0.001), longer duration of diabetes (χ 2  = 1084, p < 0.001), and type 1 diabetes (OR = 3.9, p  = 0.01). There was a statistically significant variation of DR by geographic zones (χ 2  = 310, p < 0.001). Laser treatment coverage for STDR was 22%. Duration of diabetes ( p < 0.001), cataract surgery in the past ( p  = 0.02), and females ( p  = 0.001) were predictors of STDR. Conclusion: This model of telescreening for DR provides an additional pathway for screening and preventing diabetes-related visual morbidity in India. The data from this study can be used for epidemiologic and ophthalmic health policies related to diabetes.

Purpose: To assess the effectiveness and safety of adjunctive topical netarsudil 0.02% and latanoprostene bunod 0.024% in patients with glaucoma., Methods: A retrospective, multi-center, cohort study of patients with glaucoma treated with netarsudil 0.02% or latanoprostene bunod from five tertiary care centers. Inclusion criteria included patients with glaucoma treated with either medication as adjunctive therapy. Outcomes included mean absolute intraocular pressure (IOP) reduction and relative IOP reduction from baseline. Adverse reactions and reasons for discontinuation were reported. One-way analysis of variance, Kruskal-Wallis rank sum test, and Mann Whitney U test compared the outcomes., Results: A total of 95 eyes (95 patients) on netarsudil and 41 eyes (41 patients) on latanoprostene bunod were analyzed. Mean duration of use was 54.3 ± 28 days for netarsudil and 82.9 ± 51.2 days for latanoprostene bunod. At the final visit, mean IOP reduction was 3.9 ± 4.6 mmHg (17.5 ± 6.0%) ( p  < 0.0001) with netarsudil and 2.9 ± 3.7 mmHg (13.6 ± 16.3%) ( p  < 0.0001) with latanoprostene bunod. IOP lowering did not depend on baseline number of IOP-lowering medications. The most common reason for discontinuation was non-effectiveness in both groups., Conclusion: Similar to monotherapy, netarsudil and latanoprostene bunod demonstrated efficacy in lowering IOP when used as adjunctive therapy.

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. Orbitofacial NFs, in particular, may cause progressive, disfiguring tumors of the lid, brow, temple, face, and orbit, and clinical evidence suggests that they may have increased local aggressiveness compared to NFs developing at other sites. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We performed RNA-sequencing in orbitofacial (n = 10) and non-orbitofacial (n = 9) NFs. Differential gene expression analysis demonstrated that a variety of gene sets including genes involved in cell proliferation, interferon, and immune-related pathways were enriched in orbitofacial NF. Comparisons with publicly available databases of various Schwann cell tumors and malignant peripheral nerve sheath tumor (MPNST) revealed a significant overlap of differentially expressed genes between orbitofacial versus non-orbitofacial NF and plexiform NF versus MPNST. In summary, we identified gene expression differences between orbitofacial NF and NFs occurring at other locations. Further investigation may be warranted, given that orbitofacial NF are notoriously difficult to treat and associated with disproportionate morbidity., (© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Purpose: The purpose of the study was to determine knowledge, practice, and resources available to primary care physicians to diagnose and manage corneal abrasion in Saudi Arabia., Methods: This cross-sectional survey was held in 2017. Family physicians and emergency physicians attending an international conference were surveyed. The questions related to demography, invagination, and tools available in their institute were collected. The questionnaire on how to diagnose and how they manage case of corneal abrasion was also collected using tablet-based software., Results: Two hundred and twenty-five participants participated in the survey. Exposure to eye patients in two-third of participants was too low (93; 39.6%). Resources for diagnosing corneal abrasion were available in limited centers (51; 21.7%). The rate of good practice to manage corneal abrasion was 21.2% (95% confidence interval 16.0; 26.5). Certified emergency physicians ( P < 0.001) and western and central regions ( P < 0.001) were positively associated with good practice. Availability of slit lamp ( P = 0.2) was not significantly associated with the level of practice to manage corneal abrasion. Fluorescein staining and use of cobalt blue light are essential for diagnosing corneal abrasion as per 40% of participants. About 44.7% of participants replied that antibiotics and lubricants should be used to treat. Nearly one-fourth of participants suggested urgent reference to the ophthalmologist. Use of specific antibiotic varied widely; however, ofloxacin was the main choice of antibiotic in treating corneal abrasion., Conclusion: The knowledge and practice among physicians about corneal abrasion were low. Integrating primary eye care into emergency services through provision of required resources and training physicians is recommended., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Middle East African Journal of Ophthalmology.)

Purpose: This study was to report the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in managing corneal endothelial disorders in children less than 14 years of age., Methods: Medical records of 180 DSAEK performed, between 2008 and 2020, on 167 eyes of 111 children who had a visually significant endothelial dysfunction were retrospectively reviewed for the primary etiology of corneal decompensation, time of the onset and duration of cloudiness, preoperative visual acuity, the technique of endothelial keratoplasty, surgical modifications, and reintervention., Results: Median age at surgical intervention was 7.9 years (interquartile range, 5.2-11.2 years). At a median postinterventional follow-up of 2.5 years (interquartile range, 0.9-3.4 years), 86.2% (144 of 167 eyes, 95% confidence interval 79.9%-90.1%) maintained a clear graft. Median best-corrected visual acuity (logarithm of the minimum angle of resolution) improved from 1.45 ± 0.70 preoperatively to 0.90 ± 0.06 at the last follow-up visit (P < 0.0001). The cumulative overall long-term graft survival was 92.7%, 86.5%, and 77.7% at 1, 3, and 7 years, respectively. Cox proportional hazards regression analysis showed that the indication for DSAEK (P = 0.007; hazards ratio: 2.17 ± 0.62), age at surgery (P = 0.02; hazards ratio: 0.87 ± 0.05), and any subsequent intervention after DSAEK (P = 0.003; hazards ratio: 0.11 ± 0.08) were significant risk factors for DSAEK failure. The endothelial cell loss was 40.1% at 6 months, 45.4% at 1 year, 55.2% at 5 years, and 61.9% at 7 years., Conclusions: DSAEK is a safe and effective surgical strategy in managing endothelial disorders among the pediatric age group., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To characterize the proteome of the iris in primary angle closure glaucoma (PACG)., Experimental Design: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log 2 two-fold difference in expression in iris between PACG and controls., Results: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls., Conclusions and Clinical Relevance: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG., (© 2021 Wiley-VCH GmbH.)

Purpose: The purpose of this study was to report the clinicopathological features of Peters anomaly in a child with nail-patella syndrome., Methods: Nail-patella syndrome (NPS) is a rare autosomal dominant connective tissue disorder characterized by several anomalies of the extremities, joints and nails, glomerulopathy, and rarely ocular involvement. NPS is caused by heterozygous loss-of-functional mutations in the LMX1B gene that encodes the LIM homeodomain proteins., Results: This case reports a new association of Peters anomaly in a child with NPS that also had classic skeletal/nail anomalies and protein losing nephropathy. Furthermore, DNA sequence analysis identified a novel missense heterozygous mutation in the LMX1B gene (Transcript ID: NM&#95;001174146) resulting in the replacement of tryptophan by serine in codon 266, suggesting that the mutation (p.Trp.266Ser) affects LMX1B function by disturbing its interactions with other proteins. To the best of our knowledge, this association of Peters anomaly is novel and has not been reported earlier in the ophthalmic and systemic literature on NPS., Conclusion: The corneal findings in our case with NPS are similar to those seen in congenital corneal opacification because of Peters anomaly. This novel association of Peters anomaly with NPS may be related to the effects of the LMX1B mutation on corneal development., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To evaluate and compare the clinical and histopathological profile of primary and recurrent orbital-periorbital plexiform neurofibromas (OPPN) in patients with neurofibromatosis type 1. We retrospectively evaluated 43 primary or recurrent neurofibroma (NF) specimens from 26 patients (2002 to 2018) at the King Khaled Eye Specialist Hospital, Saudi Arabia. Demographics, clinical presentation, and surgical intervention data were collected. Histopathological specimens were studied with hematoxylin-eosin, Alcian blue, and immunohistochemical markers; S-100, CD44, CD117, smooth muscle actin (SMA), neurofilament, and Ki-67. Of the 43 NFs specimens, 20 were primary and 23 recurrent tumors. For primary NF, the ratio of plexiform to the diffuse type was 13:7, however in recurrent tumors was 3:8 after the first recurrence, and 1:5 after multiple recurrences. Of the 17 patients with primary tumors that had paired recurrent tumors, 12/17 (70.6%) primary NFs were plexiform and 5/17 (29.4%) were diffuse. However, when tumors recurred, 13/17 tumors (76.5%) were diffuse and only 4/17 tumors (23.5%) had a plexiform pattern. The odds of a tumor having a diffuse pattern in recurrent NF was significantly higher than the plexiform pattern [OR = 7.8 (95% confidence interval 1.69:36.1) P = 0.008]. Primary plexiform NFs underwent an excision at a significantly younger age than the diffuse type. Recurrent NFs had significantly higher CD44, CD117, and neurofilament labeling (P = 0.02, P = 0.01 and P<0.001 respectively) but had significantly decreased Alcian blue, and S-100 labeling (P = 0.03, and P = 0.02 respectively) compared to primary tumors. SMA and Ki-67 proliferation index were not different between primary and recurrent NFs (P = 0.86, and P = 0.3 respectively). There appears to be a high risk for primary plexiform NFs to develop a diffuse histologic pattern when they recur. Immunohistochemical staining suggests a role of mast cells (CD117) and expression of infiltration makers (CD44) in the transformation of plexiform tumors to the diffuse phenotype., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study aimed to present the outcomes of the therapeutic interventions for neovascular glaucoma (NVG) between 2002 and 2012 at a tertiary eye hospital in Saudi Arabia., Methods: A retrospective chart review of the patients with NVG treated in the last 10 years at King Khaled Eye Specialist Hospital was carried out. The demographics, visual acuity, and intraocular pressure (IOP) at the baseline were compared to that, at last, follow-up. The clinical course of treated eyes and causes for poor vision were reviewed., Results: Among 597 eyes with NVG, the mean IOP at presentation was 32 mmHg. A total of 335 eyes (56.1%) were treated with pan-retinal photocoagulation (PRP). In 459 (77%) eyes, IOP was controlled with medications or different surgeries. The vision on the last follow-up was 20/20 to 20/40 in 19 (3%) eyes, 20/50 to 20/200 in 67 (11%) eyes, <20/200 to 20/400 in 267 (45%) eyes, and <20/400 in 225 (38%) eyes. Nineteen eyes were soft/enucleated. In 45 (8%, 95% CI 6-10) eyes vision improved. The IOP was reduced to <22 mmHg in 369 (62%, 95% CI 58.2-65.9) eyes, 23-30 mmHg in 69 (12%) eyes and was > 31 mmHg in 102 (17%) eyes. In 26 (3.7%) eyes, ocular hypotony was noted. The causes of poor vision included retinal ischemia (n=75, 13%), optic nerve head cupping (n=104, 17%), retinal detachment (n= 42, 7%) and other (n=17, 3%)., Conclusion: The NVG is a serious ocular ischemic complication. Prompt therapy maintained or improved the vision and controlled IOP in 50% and more cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, AlRubaie et al.)

Purpose: Mesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow-derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits., Methods: Human bone marrow-derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes., Results: The viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection., Conclusions: Subconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models., Translational Relevance: These results provide preclinical data to support a phase I clinical study.

Purpose: To evaluate medication and follow-up adherence in incarcerated patients examined at an academic glaucoma clinic, in comparison to nonincarcerated controls., Methods: Retrospective, case-control study. Consecutive prisoners presenting for initial visits in the Glaucoma Clinic at the Illinois Eye and Ear Infirmary between December 2015 and December 2017 were included in the study. Nonincarcerated patients seen in the same Glaucoma Clinic with similar initial visit dates, age, race, sex, and disease severity were selected as controls. Glaucoma Clinic visits from each patient were reviewed until December 2018. Examination information, surgical intervention, follow-up and treatment recommendations, and patient-reported medication usage were recorded for each visit. Number of visits, loss to follow-up, follow-up delays, and medication nonadherence were studied as primary outcome measures., Results: Twenty-four prisoners and 24 nonincarcerated controls were included. Prisoners had an average of 2.46 ± 2.38 visits during the study period, compared to 5.04 ± 3.25 for controls ( P = 0.001). Follow-up visits occurred more than 30 days after the recommended follow-up time in 57.4% (95% confidence interval [CI]: 44.2%-70.6%) of prisoners, compared to 17.9% (95% CI: 10.2%-25.6%) of controls ( P < 0.00001). 70.8% of prisoners (95% CI: 66.3-74.5%) were lost to follow-up, compared to 29.2% of controls (95% CI: 25.5%-32.9%; P < 0.01). Medication nonadherence rates were similar between prisoners (13.6%; 95% CI: 12.1%-15.2%) and controls (12.0%; 95% CI: 11.4%-12.6%; P = 0.78)., Conclusions: Glaucoma follow-up adherence was significantly worse in prisoners compared to a nonincarcerated control population. Further study into causative factors is needed., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Current Ophthalmology.)

Purpose: To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition., Methods: Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality., Results: Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis ( p  = 0.037) using the 8th edition criteria but not with the 7th edition ( p  = 0.066). The 8th edition T categorization significantly correlated with eye survival ( p  = 0.022) while the 7th edition did not ( p  = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis ( p  = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death ( p  = 0.281, p  = 0.737, p  = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation ( p  = 0.001), and papillary histologic pattern ( p  = 0.024) but not with pagetoid spread ( p  = 0.056)., Conclusion: The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Purpose: To evaluate the baseline features associated with blindness in a cohort of children with primary congenital glaucoma (PCG) from a hospital registry., Design: Retrospective clinical cohort study., Methods: Setting: Observational cohort study. StudyPopulation: The registry included all children who presented to our tertiary care institute between 1995 and 2014 with a diagnosis of childhood glaucoma. ObservationProcedure: Baseline characteristics at initial presentation of children with PCG in the registry who were blind at the last follow-up were compared with those who were not blind, using bivariate and then multivariate regressions to account for potential confounders. MainOutcomeMeasures: Blindness was defined as a best-corrected visual acuity of 3/60 (20/400) or worse in the better eye at the final follow-up., Results: The eligible sample consisted of 196 children with a mean age of 9.54 ± 22.44 months at presentation. After a mean ± standard deviation follow-up of 8.49 ± 3.85 years, 20 (10.2%) children were blind. The baseline demographic factors, intraocular pressure, horizontal corneal diameter, spherical equivalent, axial length, and corneal thickness, were similar for the "blind" and "not blind" groups (P > .05). In the multivariate regression, only the severity of corneal opacification remained significantly (P < .001) associated with the risk of blindness (odds ratio = 4.05; 95% confidence interval: 1.89-8.85)., Conclusion: Corneal clouding is a predictor of future blindness in children with PCG. Children with severe corneal clouding may need more aggressive intraocular pressure control, closer follow-up, and earlier counseling., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ocular pterygium-digital keloid dysplasia (OPDKD) presents in childhood with ingrowth of vascularized connective tissue on the cornea leading to severely reduced vision. Later the patients develop keloids on digits but are otherwise healthy. The overgrowth in OPDKD affects body parts that typically have lower temperature than 37°C. We present evidence that OPDKD is associated with a temperature sensitive, activating substitution, p.(Asn666Tyr), in PDGFRB. Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibroblasts at 37°C but were further greatly increased at the average corneal temperature of 32°C. This suggests that the substitution cause significant constitutive autoactivation mainly at lower temperature. In contrast, a different substitution in the same codon, p.(Asn666Ser), is associated with Penttinen type of premature aging syndrome. This devastating condition is characterized by widespread tissue degeneration, including pronounced chronic ulcers and osteolytic resorption in distal limbs. In Penttinen syndrome fibroblasts, equal and high levels of phosphorylated PDGFRB was present at both 32°C and 37°C. This indicates that this substitution causes severe constitutive autoactivation of PDGFRB regardless of temperature. In line with this, most downstream targets were not affected by lower temperature. However, STAT1, important for tissue wasting, did show further increased phosphorylation at 32°C. Temperature-dependent autoactivation offers an explanation to the strikingly different clinical outcomes of substitutions in the Asn666 codon of PDGFRB., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The Aurolab ® aqueous drainage implant is a low-cost alternative to the Baerveldt glaucoma implant. The aim of this study was to test the hypothesis that the two implants are comparable in terms of surgical success and safety., Methods: We conducted a retrospective case-control study of Aurolab aqueous drainage implant done at our institution from May 2015 and May 2017. Twenty-five consecutive patients who received an Aurolab aqueous drainage implant were matched by age and diagnosis to patients who received a Baerveldt glaucoma implant. Data were collected pre-operative and post-operative visits, including visual acuity and intraocular pressure, number of medications, and complications. Surgical success was defined as intraocular pressure between 5 and 21 mmHg with a minimum 20% reduction from baseline, without loss of light perception or the need for further glaucoma surgery. Cox regression analysis was used to predict factors associated with surgical success., Results: The median (interquartile range, IQR) intraocular pressure at 1 year was 16.0 (8.0) mmHg for the Baerveldt glaucoma implant and 13.0 (8.0) mmHg for the Aurolab aqueous drainage implant, p = 0.38. Success (mean ± SE) at 1 year for the intraocular pressure >21-mmHg failure criterion was 65% ± 15% for the Baerveldt glaucoma implant and 79% ± 11% for the Aurolab aqueous drainage implant (p = 0.80). The frequency of complications listed was similar for the two groups (Fisher's exact p = 0.71). In the Cox regression, the type of implant was not found to be associated with surgical success., Conclusions: Our preliminary results suggest that the Aurolab aqueous drainage implant is comparable to the Baerveldt glaucoma implant. Further long-term data in a larger population are needed to confirm these findings.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness., Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function., Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome., Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function., Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses., Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome., Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.