Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis.

OBJECTIVES: To identify molecular pathways and prognostic- and diagnostic plasma-protein biomarkers for diabetic retinopathy at various stages. METHODS: This exploratory, cross-sectional proteomics study involved plasma from 68 adults, including 15 healthy controls and 53 diabetes patients for various stages of diabetic retinopathy: non-diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and diabetic macular edema. Plasma was incubated with peptide library beads and eluted proteins were tryptic digested, analyzed by liquid chromatography-tandem mass-spectrometry followed by bioinformatics. RESULTS: In the 68 samples, 248 of the 731 identified plasma-proteins were present in all samples. Analysis of variance showed differential expression of 58 proteins across the five disease subgroups. Protein-Protein Interaction network (STRING) showed enrichment of various pathways during the diabetic stages. In addition, stage-specific driver proteins were detected for early and advanced diabetic retinopathy. Hierarchical clustering showed distinct protein profiles according to disease severity and disease type. CONCLUSIONS: Molecular pathways in the cholesterol metabolism, complement system, and coagulation cascade were enriched in patients at various stages of diabetic retinopathy. The peroxisome proliferator-activated receptor signaling pathway and systemic lupus erythematosus pathways were enriched in early diabetic retinopathy. Stage-specific proteins for early - and advanced diabetic retinopathy as determined herein could be 'key' players in driving disease development and potential 'target' proteins for future therapies. For type 1 and 2 diabetes mellitus, the proteomic profiles were especially distinct during the early disease stage. Validation studies should aim to clarify the role of the detected molecular pathways, potential biomarkers, and potential 'target' proteins for future therapies in diabetic retinopathy.

Botulinum Toxin A Injection for Convergence Insufficiency.

PURPOSE: To evaluate the effects of botulinum toxin A injection in one or both lateral rectus muscles in patients with convergence insufficiency previously managed with non-surgical and/or surgical options other than botulinum toxin A injection. METHODS: All patients with symptomatic convergence insufficiency treated with botulinum toxin A injection to one or both lateral rectus muscles from 2013 to 2018 at the Department of Ophthalmology, Rigshospitalet-Glostrup, Copenhagen University Hospital were retrospectively reviewed. All patients had near symptoms and were previously treated with a combination of convergence exercises, prisms, and/or surgery. Patients with previous botulinum toxin A injection in an extraocular muscle were excluded. Reading symptoms and deviation at near and distance were recorded at baseline and after 1 and 6 months. RESULTS: Twenty-three patients with convergence insufficiency were included (8 men and 15 women). Follow-up was conducted after a median of 47 days (interquartile range [IQR]: 31.5 to 72.5 days) and 174 days (IQR: 139 to 267 days). At baseline, median near angle of deviation was 18 PD of exophoria (IQR: 13 to 21 PD). The near deviation was reduced to 10 PD of exophoria (IQR: 7 to 17 PD) at first follow-up visit and 14 PD of exophoria (IQR: 12 to 18 PD) at last follow-up visit. Thirteen of 23 patients (57%) and 3 of 13 patients (23%) reported improvement in reading symptoms at first and last follow-up visit, respectively, compared to baseline. CONCLUSIONS: Botulinum toxin A injection may be useful in patients with convergence insufficiency. However, some patients may require repeated injections. [J Pediatr Ophthalmol Strabismus. 2023;60(2):108-113.].

Strabismus surgery alleviates functional and psychosocial problems.

Strabismus is a common condition affecting both children and adults. Strabismus patients may experience double vision, abnormal head position and loss of stereovision. The psychosocial negative impact of strabismus may be severe, affect self-esteem, social relationships, and job opportunities. Strabismus is a congenital condition or a result of an illness in later life and surgical treatment should be considered as reconstructive surgery and not downrated as just ¼a cosmetic procedure«. Strabismus surgery is safe, effective and addresses functional as well as psychosocial problems.

Laser pointer maculopathy - on the rise?

PURPOSE: To report symptoms and ocular pathology in 13 patients exposed to light from laser pointers. METHODS: We conducted a multi-centre consecutive case series from eight ophthalmology departments. RESULTS: Eleven boys aged 9-15 years and two girls aged 7 (sister of one of the aforementioned boys) and 12 years, respectively, were included. Laser wavelengths were 572 nm (green), 450 nm (blue), and red laser of unknown wavelength. Output powers were between 5 and 5000 mW. Evaluation included slit lamp examination, colour fundus photography (CFP), and optical coherence tomography (OCT). All subjects complained of unilateral vision loss. Initial visual acuities in exposed eyes ranged from 0.05 to 1.0 Snellen equivalent or better. Nine subjects showed pathology on CFP and OCT abnormalities. One subject had a macular hole, which closed after vitrectomy. Long-term visual acuity ranged from 0.3 to 1.0 Snellen equivalent or better. CONCLUSION: High-powered laser pointers have become readily available on the internet, and they have the potential to induce lasting visual loss. More than half of the published laser pointer maculopathy cases since the first incidence in 1999 have been published in 2014-2017. We suspect that incidence of exposure and subsequent visual loss is rising, and we encourage national legislators to regulate this market.

The Forgotten Syndrome? Four Cases of Gradenigo's Syndrome and a Review of the Literature.

BACKGROUND: Gradenigo's Syndrome (GS) is defined as the clinical triad of acute otitis media, ipsilateral sixth nerve palsy, and pain in the distribution of the first and the second branches of the fifth nerve. The purpose of this study is to review the literature and report 4 cases of GS. METHODS: The study is a retrospective case series and a review of the literature. Four consecutive patients (aged 5-70 years) treated by otolaryngologists and ophthalmologists for GS in the Capital region of Denmark from 2003 to 2015 are presented. Diagnosis is based on the clinical triad, and in 3 of 4 patients, neuroimaging supports the diagnosis. Follow-up was continued until both the sixth nerve palsy and the ear infection had resolved. Diagnostic work-up and treatment profile are described. RESULTS: In 3 of our 4 reported patients, the presentation of GS was classic with a history of acute otitis media and ipsilateral sixth nerve palsy. One case presented as a chronic case with a sixth nerve palsy secondary to chronic suppurative otitis media (CSOM), with a relapse 6 years later. CONCLUSION: GS is a rare and potentially life-threatening complication to otitis media. GS can present in an acute and chronic form, and should be a differential diagnosis in the workup of unexplained sixth nerve palsy.

Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency.

INTRODUCTION: We evaluated the use of botulinum toxin A in adults with convergence insufficiency in whom prior treatment had failed. METHODS: We studied 8 patients (median age 36 years, range 17 to 77 years) with reading symptoms due to convergence insufficiency defined as an exodeviation greater at near, not exceeding 10 PD in the distance measured by prism and alternate cover test, and either convergence near point>6 cm or reduced fusional amplitudes. All patients were still symptomatic after prior treatment by convergence exercises (n=8), base-in prism glasses (n=5) or strabismus surgery (n=2). Five patients received injection of 5 IU botulinum toxin in 0.1 ml saline to one lateral rectus muscle, two received 2.5 IU, and one received 2.5 IU to both lateral rectus muscles. RESULTS: At 1 month post injection, all patients had an initial reduction of exodeviation from baseline (median 9 PD, p=0.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p=0.3) at near. Reading symptoms improved in 7 of 8 patients at 1-month post injection, and in all patients at 6 months. Two patients had health-related quality of life assessed with the Adult Strabismus 20 Questionnaire, showing improved Reading Function scores at 6 months. Interestingly, 3 patients reported improved reading despite returning to the baseline angle at 6 months, and 2 of 4 with 12-month follow-up still reported improvement. CONCLUSIONS: In adult convergence insufficiency, botulinum toxin injection to a lateral rectus muscle improves reading symptoms beyond the duration of the pure pharmacological effect. Botulinum toxin injection may be useful in management of adult convergence insufficiency, although repeat injections may be needed.

33 cases of airsoft gun pellet ocular injuries in Copenhagen, Denmark, 1998-2002.

PURPOSE: To evaluate the incidence and ocular effects of blunt trauma due to injury from airsoft gun pellets. METHODS: We conducted a non-comparative case series based on the files of 33 patients who suffered ocular injury from airsoft guns and were admitted to one university emergency eye clinic in Copenhagen during a 5-year period. RESULTS: A total of 33 eyes in 33 patients were examined. Thirty male and three female patients were affected. Mean age was 13 years (range 3-49 years). Mean follow-up time was 6.5 days (range 1-540 days). On initial examination, we found: hyphaema (n = 28), corneal abrasion (n = 22), retinal oedema (n = 11), subconjunctival haemorrhage (n = 10), palpebral haemorrhage and/or oedema (n = 9), iris dialysis (n = 7), intraocular pressure (IOP) > 31 mmHg (n = 4), IOP < 9 mmHg (n = 4), vitreous haemorrhage (n = 2) and cataract (n = 1). One patient had brown corneal discoloration due to severe chronic hyphaema that required surgery. The final visual acuity was 1.0 in 20 patients and < or = 0.7 in five patients. CONCLUSION: The airsoft gun trauma resulted in anterior and posterior segment ocular injuries that required acute medical intervention and for which some patients were hospitalized. Trauma mainly occurred in children and youths. A longterm risk of glaucoma is expected. Eye care professionals and parents as well as manufacturers of airsoft guns should advise participants to wear adequate protection when involved in this activity.